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Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Condition aggravated'. | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | ATORVASTATIN, BEVACIZUMAB, DEXAMETHASONE, FLUOROURACIL, IRINOTECAN | DrugsGivenReaction | CC BY-NC-ND | 30074937 | 19,733,043 | 2021-07-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Lipaemia retinalis'. | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | ATORVASTATIN, BEVACIZUMAB, DEXAMETHASONE, FLUOROURACIL, IRINOTECAN | DrugsGivenReaction | CC BY-NC-ND | 30074937 | 19,733,043 | 2021-07-01 |
What was the administration route of drug 'DEXAMETHASONE'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | Intravenous (not otherwise specified) | DrugAdministrationRoute | CC BY-NC-ND | 30074937 | 19,656,418 | 2021-07-01 |
What was the dosage of drug 'ATORVASTATIN'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | 40 mg (milligrams). | DrugDosage | CC BY-NC-ND | 30074937 | 19,733,043 | 2021-07-01 |
What was the dosage of drug 'BEVACIZUMAB'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | SIX CYCLES | DrugDosageText | CC BY-NC-ND | 30074937 | 19,656,418 | 2021-07-01 |
What was the dosage of drug 'FLUOROURACIL'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | SIX CYCLES | DrugDosageText | CC BY-NC-ND | 30074937 | 19,656,418 | 2021-07-01 |
What was the dosage of drug 'IRINOTECAN'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | SIX CYCLES | DrugDosageText | CC BY-NC-ND | 30074937 | 19,656,418 | 2021-07-01 |
What was the outcome of reaction 'Condition aggravated'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | Recovered | ReactionOutcome | CC BY-NC-ND | 30074937 | 19,733,043 | 2021-07-01 |
What was the outcome of reaction 'Hyperlipidaemia'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | Recovered | ReactionOutcome | CC BY-NC-ND | 30074937 | 19,656,418 | 2021-07-01 |
What was the outcome of reaction 'Lipaemia retinalis'? | LIPEMIA RETINALIS DURING CHEMOTHERAPY WITH ADJUNCTIVE GLUCOCORTICOID TREATMENT IN A PATIENT WITH COLON CARCINOMA.
OBJECTIVE
The purpose of this report is to describe a case of lipemia retinalis due to decompensating hyperlipidemia that occurred during chemotherapy in a patient with metastatic colon carcinoma.
METHODS
Retrospective case report.
RESULTS
A 55-year-old non-insulin-dependent diabetic man with well-controlled hyperlipidemia presented himself with temporarily blurred vision in both eyes occurring during chemotherapy. He was found to have lipemia retinalis in his both eyes. Blood tests revealed elevated cholesterol and triglyceride levels exceeding 8,200 mg/dL. He received six cycles of FOLFIRI/bevacizumab and accompanying dexamethasone because of colon cancer with pulmonary metastases. Lipemia retinalis had resolved after a 6-week follow-up when chemotherapy was finished, and the patients' triglyceride and glucose levels decreased to normal values.
CONCLUSIONS
Lipemia retinalis associated with visual impairment may occur during chemotherapy under accompanying treatment with dexamethasone. Even if patients with hyperlipidemia are metabolically well-controlled with oral medication, treatment with dexamethasone can potentially lead to decompensation of hyperlipidemia causing secondary lipemia retinalis.
Hyperlipidemia is characterized by increased levels of serum concentrations of cholesterol or triglycerides and known as a major factor of premature vessel atherosclerosis. Lipemia retinalis is a rare retinal manifestation of hypertriglyceridemia. Retinal vessels appear creamy whitish colored due to the effect of light scattering by triglyceride-laden chylomicrons.1 In clinical practice, lipemia retinalis caused by chylomicronemia in hyperlipidemia is often observed in patients with metabolic syndrome. However, associations with primary hyperlipidemia or secondary factors causing high levels of triglycerides are also well-documented.2,3
Case Report
A 55-year-old white man presented to our department with temporarily blurred vision in both eyes. Ocular history of the patient was unremarkable, and his best-corrected visual acuity was 100/100 in both eyes. Slit-lamp examination demonstrated normal anterior segments, and intraocular pressures were measured at 16 mmHg in both eyes. His medical history included metastatic colon cancer treated with surgery and chemotherapy, diabetes mellitus, and hyperlipidemia well-controlled with statins (atorvastatin 40 mg once per day).
Dilated funduscopic examination revealed normal optic discs, white creamy retinal vessels, and arterial narrowing with arteriovenous crossing abnormalities but no signs of diabetic retinopathy. Furthermore, optical coherence tomography was unremarkable, and there was no evidence for diabetic macular edema. The clinical picture was consistent with lipemia retinalis (Figure 1, A and B).
Fig. 1. Fundus photograph of right (A) and left (B) eye with signs of lipemia retinalis. Characteristic white creamy vessels are visible, making it difficult to distinguish the arteries from the veins.
Before our ophthalmologic examination, the patient was treated with six cycles of chemotherapy with FOLFIRI/bevacizumab because of newly occurring pulmonary metastases. The chemotherapy consisted of bevacizumab, irinotecan, and 5-fluorouracil. In addition, he received intravenous therapy with dexamethasone (8 mg every 2 weeks) for treatment of the side effects of the chemotherapy. The patient was referred to the Department of Internal Medicine to perform further diagnosis and treatment; were laboratory evaluation revealed highly increased levels of cholesterol (681 mg/dL) and triglycerides (8,258 mg/dL). It seems the chemotherapy with concomitant treatment with dexamethasone led to metabolic decompensation in hyperlipidemia.
The patient presented himself again to our department 6 weeks later, reporting that his visual problems had vanished. Fundus examination revealed reversion of the alterations of the retinal vessels due to lipemia (Figure 2, A and B). Metabolic control of the triglycerides was achieved (triglycerides were 605 mg/dL and cholesterol was 167 mg/dL on the day of examination) since he quitted chemotherapy and intravenous dexamethasone. In addition, his lipid-lowering therapy had been re-evaluated and changed to cholib 145/40 mg tablets once per day (combination of simvastatin and fenofibrate).
Fig. 2. Fundus photograph of right (A) and left (B) eye, 6 weeks after initial presentation and under appropriate lipid-lowering medication. The lipemia retinalis had resolved, and the retinal vessels abnormalities returned to normal appearance.
Discussion
Lipemia retinalis is a rare ocular finding characterized by creamy white colored retinal blood vessels, which was first described in 1880 by Heyl.4 It is associated with elevated levels of plasma triglycerides and occurs in certain types of both primary and secondary hyperlipidemia. In early stages of lipemia retinalis (triglyceride levels of 2,500–3,499 mg/dL), only the peripheral retinal vessels appear creamy and thin. As triglyceride levels increase (3,500–5,000 mg/dL), lipemia spreads out to the posterior pole and the creamy color of the vessels extends toward the optic disc. With triglyceride levels exceeding 5,000 mg/dL, the retina becomes salmon-colored with creamy whitish arteries and veins distinguishable only by size.1,2
Although the exact correlation of the incidence of lipemia retinalis and the level of plasma triglycerides is not completely understood, the retinal changes are known as a direct consequence of the elevated levels of circulating chylomicrons in the retinal vessels. Chylomicrons are large lipoproteins, which serve to transport triglycerides in the circulatory system after intestinal absorption. The slightly smaller macromolecules very low-density lipoproteins also play an important role. These lipoproteins are involved in the process of transportation of fat in the metabolism but do not seem to contribute to the fundal appearance.5
However, it has been observed that not all patients with even highly elevated levels of chylomicrons and triglycerides present lipemia retinalis, suggesting that other factors, such as changes in hematocrit and difference in translucency of the retinal and choroidal vessels, have to be considered.5 Rayner et al1 assumed the light-scattering effect of chylomicrons is responsible for the clinical picture of lipemia retinalis in the fundi.
Most lipemia retinalis cases are asymptomatic, but in fact, also patients with initially deteriorated visual acuity were reported.6 In general, only advanced and persistent lipemia is known to cause decrease in visual acuity or might even lead to complete loss of vision after massive irreversible lipid exsudation.1
Regarding current literature, several cases of lipemia retinalis caused by chylomicronemia in hyperlipidemia due to uncontrolled diabetes mellitus or due to primary hyperlipidemia or even caused by impairment of lipid metabolism during a viral illness were described.1,3
This is the first report to our knowledge of an association between symptomatic lipemia retinalis and decompensated hyperlipidemia related to treatment with chemotherapy and accompanying treatment with dexamethasone in a patient with metastatic colon cancer. The present data do not reveal any causal linkage between chemotherapy with FOLFOX/bevacizumab and secondary hyperlipidemia, so lipemia retinalis in our patient is believed to be a consequence of decompensated hyperlipidemia after chronic therapy with dexamethasone over a period of 5 months.
Previously, Chahande et al described a case of a 14-year-old diabetic boy developing lipemia retinalis because of intravenous treatment with prednisolone (1 mg/kg for 5 days) for multiple intracranial neurocysticerci with perilesional edema. The authors also assume the lipemia in this case was caused by administration of steroids.7
Secondary hypertriglyceridemia is known as a result of the supply of glucocorticoids. Glucocorticoid substitution is associated with hypertriglyceridemia, elevated glucose, and higher non–high-density lipoprotein cholesterol levels and can lead to metabolic syndrome, which was proved in a study with GH- and glucocorticoid-replaced hypopituitary patients.8
Suggesting underlying mechanisms, studies reported that pharmacological doses of glucocorticoids lead to an increased endogenous glucose production in healthy people by stimulating hepatic gluconeogenic enzymes and augmenting supply of substrates to the liver for gluconeogenesis by peripheral lipolysis and proteolysis.9,10
Usually no treatment is required for lipemia retinalis. Once triglyceride levels return to normal, the retinal appearance of lipemia retinalis should quickly resolve without causing decrease in visual acuity or permanent retinal disease.11 However, lipemia retinalis is a very important sign of a potential life-threatening systemic metabolic disorder, and it is essential to recognize it as a sign of a profound lipid abnormality.
We present the first documentation of lipemia retinalis associated with visual symptoms because of decompensating hyperlipidemia in a patient undergoing chemotherapy with concomitant treatment with dexamethasone, and we want to raise awareness of this probably often underdiagnosed retinal condition. Lipid-lowering therapy is believed to normalize fundal appearance and leads to restoration of visual acuity. It is important to adapt the lipid-lowering medication to obtain appropriate management of the lipid metabolism in patients receiving dexamethasone therapy.
None of the authors has any financial/conflicting interests to disclose. | Recovered | ReactionOutcome | CC BY-NC-ND | 30074937 | 19,733,043 | 2021-07-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Drug ineffective'. | BULL'S EYE MACULOPATHY POSSIBLY DUE TO IRON OVERLOAD IN A CHILD WITH THALASSEMIA MAJOR: A CASE OF POSSIBLE "FERRITIN RETINOPATHY".
OBJECTIVE
To report a case of bull's eye maculopathy probably caused by iron overload in a child with thalassemia major.
METHODS
Case report.
RESULTS
A 6-year-old girl with thalassemia major who was on chronic multiple blood transfusions since 2 years of age presented with blurred vision in both eyes for 2 months. Blood reports showed very high serum ferritin levels in the range 400 to 2,250 ng/mL (checked every 3 months) since 4 years of age. She was on oral iron chelator deferasirox for 2 years, which was stopped a month ago. Fundus examination of both eyes showed a characteristic bull's eye macula with a purplish hue in the outer ring probably due to iron deposition. The center of the bull's eye had a beaten bronze appearance.
CONCLUSIONS
Careful history-taking is important in children with bull's eye maculopathy because all such retinopathies need not be hereditary fundus dystrophies. Further progression can be arrested by identifying and removing the cause vision loss.
Bull's eye maculopathy is a term given to describe the appearance of the macula as a target or bull's eye. Degeneration of the retinal pigment epithelium (RPE) in the macular area causes alternating ring-like light and dark zones of pigmentation. This is the first case described to the best of our knowledge of bull's eye maculopathy probably caused due to serum iron overload in a child with thalassemia major.
Case Report
A 6-year-old girl of Indian origin, diagnosed to have beta thalassemia major at birth, presented with gradual decrease in vision in both eyes, especially for distance since 2 months. She had undergone multiple blood transfusions, and on repeated testing, her serum ferritin levels were between 400 ng/mL and 2,250 ng/mL checked every 3 months (normal range 7–140 ng/mL). She was using oral iron chelators deferasirox at 125 mg/day for 2 years, which was stopped a month back. Serum ferritin levels did not reach normal despite oral chelators.
On examination, best-corrected visual acuity was 20/100, N18 in the right eye and 20/40p, N8 in the left eye. Anterior segment examination was unremarkable. Fundus examination of both eyes showed a bull's eye pattern in the macula with a ring of purplish hue outside a circular bronze-colored zone of possible RPE atrophy (Figures 1 and 2). Optical coherence tomography of both eyes showed foveal thinning, more in the right eye, photoreceptor atrophy, and increased RPE reflectivity (Figures 3 and 4). Electroretinography showed extinguished photopic response while scotopic response was minimally affected.
Fig. 1. Fundus image of the right eye showing a purple-colored bull's eye maculopathy.
Fig. 2. Fundus image of the left eye showing a purple-colored bull's eye maculopathy.
Fig. 3. Optical coherence tomography of the right eye showing foveal and photoreceptor atrophy with underlying hyperreflectivity of the retinal pigment epithelium.
Fig. 4. Optical coherence tomography of the left eye showing foveal thinning with underlying hyperreflectivity of the RPE.
There was no history of family members affected with hereditary fundus dystrophies.
Discussion
Common causes of bull's eye maculopathy are progressive cone dystrophy, rod cone dystrophy, Stargardt dystrophy, benign concentric macular dystrophy, Batten disease, and drug-induced toxicity as in chloroquine and hydroxychloroquine retinopathy. In cone dystrophy, it is common to see a drop in visual acuity much earlier than fundus changes. Photophobia and loss of color vision are evident. With advancing age, visual acuity drops further with marked RPE atrophy in the fovea and temporal disk pallor. A bull's eye maculopathy in cone dystrophy presents as a lighter ring of RPE atrophy surrounding a dark center. In rod cone dystrophy, increased disk pallor, arteriolar attenuation, and pigmentary changes are seen in the retinal periphery, giving an appearance similar to that of retinitis pigmentosa. Night blindness occurs early in life. In Stargardt dystrophy, a beaten bronze–appearing fovea is seen with surrounding lighter RPE changes. This condition presents later in life and is rare in early childhood. Drug-induced toxicity is known to cause acquired bull's eye maculopathy.
β-Thalassemia major is a hereditary haemolytic anemia that is treated with multiple blood transfusions.1 In this condition, blood transfusions, ineffective erythropoiesis, and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload can be determined by serum ferritin measurement. In these patients, iron deposition in parenchymal tissues begins within 1 year of starting the regular transfusions.2
Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload because humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. A unit of erythrocytes transfused contains approximately 250 mg of iron, while the body cannot excrete more than 1 mg of iron per day. As iron loading progresses, the capacity of serum transferrin, the main transport protein of iron, to bind and detoxify iron may be exceeded. Thereafter, the non–transferrin-bound fraction of iron within plasma may promote generation of free hydroxyl radicals, propagators of oxygen-related damage.
Excess iron is extremely toxic to all cells of the body and can cause serious and irreversible organic damage, such as cirrhosis, diabetes, heart disease, and hypogonadism.3 Normal values of serum ferritin for men and women are 12 to 300 ng/mL and 12 to 150 ng/mL, respectively. The distribution of iron and ferritin has been characterized in the adult rat retina.3 Proton-induced X-ray emission identified the largest amounts of heme and nonheme iron in the inner segments of photoreceptors, the RPE, the choroid, the inner nuclear layer, and the ganglion cell layer. Iron was present in somewhat lesser, but still significant amounts in the photoreceptor outer segments. Interestingly, immunohistochemistry studies have demonstrated a similar distribution pattern of retinal ferritin. The exception is that iron, but not much ferritin, is contained in the photoreceptor outer segment.
Iron has an affinity for melanin in the RPE.4 Accumulation of iron in the RPE causes RPE atrophy and hence foveal and photoreceptor atrophy. The purplish hue in the outer ring of the bull's eye maculopathy seen in this child could possibly be due to iron accumulation. The center shows foveal atrophy, suggesting a loss of RPE due to previous iron accumulation.
Our patient was using oral chelator deferasirox at a dose of 125 mg/day for 2 years before she presented to us. This drug is known to cause reversible retinopathy and improvement of vision on drug withdrawal.5 This drug did not help lower the ferritin levels, which were persistently high for 2 years. Our patient had stopped oral chelators a month ago and yet noticed progressive loss of vision in both eyes. Optical coherence tomography showed foveal and photoreceptor atrophy in our patient causing permanent vision loss.
Although we do not have any conclusive evidence that suggests iron overload as the cause for the purplish hue and bull's eye appearance of the macula, we do believe this discoloration could be due to ferritin accumulation.
We feel it is important to consider raised serum ferritin as a possible cause for vision loss as correcting this can prevent further visual loss.
Conclusion
Although bull's eye maculopathy in children and young adults points to a diagnosis of hereditary degenerations in most cases, a careful examination of the pattern of bull's eye in the macula and history-taking is essential. In this case, the outer zone of the bull's eye has a classic purple hue with a central bronze zone. A careful systemic history and history of drug intake are necessary. Although oral chelators may be harmful to the RPE, it is important to note that persistently raised serum ferritin may be more harmful.
The author has no financial/conflicting interests to disclose. | DEFERASIROX | DrugsGivenReaction | CC BY-NC-ND | 30395118 | 19,834,466 | 2021-07-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Maculopathy'. | BULL'S EYE MACULOPATHY POSSIBLY DUE TO IRON OVERLOAD IN A CHILD WITH THALASSEMIA MAJOR: A CASE OF POSSIBLE "FERRITIN RETINOPATHY".
OBJECTIVE
To report a case of bull's eye maculopathy probably caused by iron overload in a child with thalassemia major.
METHODS
Case report.
RESULTS
A 6-year-old girl with thalassemia major who was on chronic multiple blood transfusions since 2 years of age presented with blurred vision in both eyes for 2 months. Blood reports showed very high serum ferritin levels in the range 400 to 2,250 ng/mL (checked every 3 months) since 4 years of age. She was on oral iron chelator deferasirox for 2 years, which was stopped a month ago. Fundus examination of both eyes showed a characteristic bull's eye macula with a purplish hue in the outer ring probably due to iron deposition. The center of the bull's eye had a beaten bronze appearance.
CONCLUSIONS
Careful history-taking is important in children with bull's eye maculopathy because all such retinopathies need not be hereditary fundus dystrophies. Further progression can be arrested by identifying and removing the cause vision loss.
Bull's eye maculopathy is a term given to describe the appearance of the macula as a target or bull's eye. Degeneration of the retinal pigment epithelium (RPE) in the macular area causes alternating ring-like light and dark zones of pigmentation. This is the first case described to the best of our knowledge of bull's eye maculopathy probably caused due to serum iron overload in a child with thalassemia major.
Case Report
A 6-year-old girl of Indian origin, diagnosed to have beta thalassemia major at birth, presented with gradual decrease in vision in both eyes, especially for distance since 2 months. She had undergone multiple blood transfusions, and on repeated testing, her serum ferritin levels were between 400 ng/mL and 2,250 ng/mL checked every 3 months (normal range 7–140 ng/mL). She was using oral iron chelators deferasirox at 125 mg/day for 2 years, which was stopped a month back. Serum ferritin levels did not reach normal despite oral chelators.
On examination, best-corrected visual acuity was 20/100, N18 in the right eye and 20/40p, N8 in the left eye. Anterior segment examination was unremarkable. Fundus examination of both eyes showed a bull's eye pattern in the macula with a ring of purplish hue outside a circular bronze-colored zone of possible RPE atrophy (Figures 1 and 2). Optical coherence tomography of both eyes showed foveal thinning, more in the right eye, photoreceptor atrophy, and increased RPE reflectivity (Figures 3 and 4). Electroretinography showed extinguished photopic response while scotopic response was minimally affected.
Fig. 1. Fundus image of the right eye showing a purple-colored bull's eye maculopathy.
Fig. 2. Fundus image of the left eye showing a purple-colored bull's eye maculopathy.
Fig. 3. Optical coherence tomography of the right eye showing foveal and photoreceptor atrophy with underlying hyperreflectivity of the retinal pigment epithelium.
Fig. 4. Optical coherence tomography of the left eye showing foveal thinning with underlying hyperreflectivity of the RPE.
There was no history of family members affected with hereditary fundus dystrophies.
Discussion
Common causes of bull's eye maculopathy are progressive cone dystrophy, rod cone dystrophy, Stargardt dystrophy, benign concentric macular dystrophy, Batten disease, and drug-induced toxicity as in chloroquine and hydroxychloroquine retinopathy. In cone dystrophy, it is common to see a drop in visual acuity much earlier than fundus changes. Photophobia and loss of color vision are evident. With advancing age, visual acuity drops further with marked RPE atrophy in the fovea and temporal disk pallor. A bull's eye maculopathy in cone dystrophy presents as a lighter ring of RPE atrophy surrounding a dark center. In rod cone dystrophy, increased disk pallor, arteriolar attenuation, and pigmentary changes are seen in the retinal periphery, giving an appearance similar to that of retinitis pigmentosa. Night blindness occurs early in life. In Stargardt dystrophy, a beaten bronze–appearing fovea is seen with surrounding lighter RPE changes. This condition presents later in life and is rare in early childhood. Drug-induced toxicity is known to cause acquired bull's eye maculopathy.
β-Thalassemia major is a hereditary haemolytic anemia that is treated with multiple blood transfusions.1 In this condition, blood transfusions, ineffective erythropoiesis, and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload can be determined by serum ferritin measurement. In these patients, iron deposition in parenchymal tissues begins within 1 year of starting the regular transfusions.2
Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload because humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. A unit of erythrocytes transfused contains approximately 250 mg of iron, while the body cannot excrete more than 1 mg of iron per day. As iron loading progresses, the capacity of serum transferrin, the main transport protein of iron, to bind and detoxify iron may be exceeded. Thereafter, the non–transferrin-bound fraction of iron within plasma may promote generation of free hydroxyl radicals, propagators of oxygen-related damage.
Excess iron is extremely toxic to all cells of the body and can cause serious and irreversible organic damage, such as cirrhosis, diabetes, heart disease, and hypogonadism.3 Normal values of serum ferritin for men and women are 12 to 300 ng/mL and 12 to 150 ng/mL, respectively. The distribution of iron and ferritin has been characterized in the adult rat retina.3 Proton-induced X-ray emission identified the largest amounts of heme and nonheme iron in the inner segments of photoreceptors, the RPE, the choroid, the inner nuclear layer, and the ganglion cell layer. Iron was present in somewhat lesser, but still significant amounts in the photoreceptor outer segments. Interestingly, immunohistochemistry studies have demonstrated a similar distribution pattern of retinal ferritin. The exception is that iron, but not much ferritin, is contained in the photoreceptor outer segment.
Iron has an affinity for melanin in the RPE.4 Accumulation of iron in the RPE causes RPE atrophy and hence foveal and photoreceptor atrophy. The purplish hue in the outer ring of the bull's eye maculopathy seen in this child could possibly be due to iron accumulation. The center shows foveal atrophy, suggesting a loss of RPE due to previous iron accumulation.
Our patient was using oral chelator deferasirox at a dose of 125 mg/day for 2 years before she presented to us. This drug is known to cause reversible retinopathy and improvement of vision on drug withdrawal.5 This drug did not help lower the ferritin levels, which were persistently high for 2 years. Our patient had stopped oral chelators a month ago and yet noticed progressive loss of vision in both eyes. Optical coherence tomography showed foveal and photoreceptor atrophy in our patient causing permanent vision loss.
Although we do not have any conclusive evidence that suggests iron overload as the cause for the purplish hue and bull's eye appearance of the macula, we do believe this discoloration could be due to ferritin accumulation.
We feel it is important to consider raised serum ferritin as a possible cause for vision loss as correcting this can prevent further visual loss.
Conclusion
Although bull's eye maculopathy in children and young adults points to a diagnosis of hereditary degenerations in most cases, a careful examination of the pattern of bull's eye in the macula and history-taking is essential. In this case, the outer zone of the bull's eye has a classic purple hue with a central bronze zone. A careful systemic history and history of drug intake are necessary. Although oral chelators may be harmful to the RPE, it is important to note that persistently raised serum ferritin may be more harmful.
The author has no financial/conflicting interests to disclose. | DEFERASIROX | DrugsGivenReaction | CC BY-NC-ND | 30395118 | 20,230,551 | 2021-07-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Therapy non-responder'. | BULL'S EYE MACULOPATHY POSSIBLY DUE TO IRON OVERLOAD IN A CHILD WITH THALASSEMIA MAJOR: A CASE OF POSSIBLE "FERRITIN RETINOPATHY".
OBJECTIVE
To report a case of bull's eye maculopathy probably caused by iron overload in a child with thalassemia major.
METHODS
Case report.
RESULTS
A 6-year-old girl with thalassemia major who was on chronic multiple blood transfusions since 2 years of age presented with blurred vision in both eyes for 2 months. Blood reports showed very high serum ferritin levels in the range 400 to 2,250 ng/mL (checked every 3 months) since 4 years of age. She was on oral iron chelator deferasirox for 2 years, which was stopped a month ago. Fundus examination of both eyes showed a characteristic bull's eye macula with a purplish hue in the outer ring probably due to iron deposition. The center of the bull's eye had a beaten bronze appearance.
CONCLUSIONS
Careful history-taking is important in children with bull's eye maculopathy because all such retinopathies need not be hereditary fundus dystrophies. Further progression can be arrested by identifying and removing the cause vision loss.
Bull's eye maculopathy is a term given to describe the appearance of the macula as a target or bull's eye. Degeneration of the retinal pigment epithelium (RPE) in the macular area causes alternating ring-like light and dark zones of pigmentation. This is the first case described to the best of our knowledge of bull's eye maculopathy probably caused due to serum iron overload in a child with thalassemia major.
Case Report
A 6-year-old girl of Indian origin, diagnosed to have beta thalassemia major at birth, presented with gradual decrease in vision in both eyes, especially for distance since 2 months. She had undergone multiple blood transfusions, and on repeated testing, her serum ferritin levels were between 400 ng/mL and 2,250 ng/mL checked every 3 months (normal range 7–140 ng/mL). She was using oral iron chelators deferasirox at 125 mg/day for 2 years, which was stopped a month back. Serum ferritin levels did not reach normal despite oral chelators.
On examination, best-corrected visual acuity was 20/100, N18 in the right eye and 20/40p, N8 in the left eye. Anterior segment examination was unremarkable. Fundus examination of both eyes showed a bull's eye pattern in the macula with a ring of purplish hue outside a circular bronze-colored zone of possible RPE atrophy (Figures 1 and 2). Optical coherence tomography of both eyes showed foveal thinning, more in the right eye, photoreceptor atrophy, and increased RPE reflectivity (Figures 3 and 4). Electroretinography showed extinguished photopic response while scotopic response was minimally affected.
Fig. 1. Fundus image of the right eye showing a purple-colored bull's eye maculopathy.
Fig. 2. Fundus image of the left eye showing a purple-colored bull's eye maculopathy.
Fig. 3. Optical coherence tomography of the right eye showing foveal and photoreceptor atrophy with underlying hyperreflectivity of the retinal pigment epithelium.
Fig. 4. Optical coherence tomography of the left eye showing foveal thinning with underlying hyperreflectivity of the RPE.
There was no history of family members affected with hereditary fundus dystrophies.
Discussion
Common causes of bull's eye maculopathy are progressive cone dystrophy, rod cone dystrophy, Stargardt dystrophy, benign concentric macular dystrophy, Batten disease, and drug-induced toxicity as in chloroquine and hydroxychloroquine retinopathy. In cone dystrophy, it is common to see a drop in visual acuity much earlier than fundus changes. Photophobia and loss of color vision are evident. With advancing age, visual acuity drops further with marked RPE atrophy in the fovea and temporal disk pallor. A bull's eye maculopathy in cone dystrophy presents as a lighter ring of RPE atrophy surrounding a dark center. In rod cone dystrophy, increased disk pallor, arteriolar attenuation, and pigmentary changes are seen in the retinal periphery, giving an appearance similar to that of retinitis pigmentosa. Night blindness occurs early in life. In Stargardt dystrophy, a beaten bronze–appearing fovea is seen with surrounding lighter RPE changes. This condition presents later in life and is rare in early childhood. Drug-induced toxicity is known to cause acquired bull's eye maculopathy.
β-Thalassemia major is a hereditary haemolytic anemia that is treated with multiple blood transfusions.1 In this condition, blood transfusions, ineffective erythropoiesis, and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload can be determined by serum ferritin measurement. In these patients, iron deposition in parenchymal tissues begins within 1 year of starting the regular transfusions.2
Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload because humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. A unit of erythrocytes transfused contains approximately 250 mg of iron, while the body cannot excrete more than 1 mg of iron per day. As iron loading progresses, the capacity of serum transferrin, the main transport protein of iron, to bind and detoxify iron may be exceeded. Thereafter, the non–transferrin-bound fraction of iron within plasma may promote generation of free hydroxyl radicals, propagators of oxygen-related damage.
Excess iron is extremely toxic to all cells of the body and can cause serious and irreversible organic damage, such as cirrhosis, diabetes, heart disease, and hypogonadism.3 Normal values of serum ferritin for men and women are 12 to 300 ng/mL and 12 to 150 ng/mL, respectively. The distribution of iron and ferritin has been characterized in the adult rat retina.3 Proton-induced X-ray emission identified the largest amounts of heme and nonheme iron in the inner segments of photoreceptors, the RPE, the choroid, the inner nuclear layer, and the ganglion cell layer. Iron was present in somewhat lesser, but still significant amounts in the photoreceptor outer segments. Interestingly, immunohistochemistry studies have demonstrated a similar distribution pattern of retinal ferritin. The exception is that iron, but not much ferritin, is contained in the photoreceptor outer segment.
Iron has an affinity for melanin in the RPE.4 Accumulation of iron in the RPE causes RPE atrophy and hence foveal and photoreceptor atrophy. The purplish hue in the outer ring of the bull's eye maculopathy seen in this child could possibly be due to iron accumulation. The center shows foveal atrophy, suggesting a loss of RPE due to previous iron accumulation.
Our patient was using oral chelator deferasirox at a dose of 125 mg/day for 2 years before she presented to us. This drug is known to cause reversible retinopathy and improvement of vision on drug withdrawal.5 This drug did not help lower the ferritin levels, which were persistently high for 2 years. Our patient had stopped oral chelators a month ago and yet noticed progressive loss of vision in both eyes. Optical coherence tomography showed foveal and photoreceptor atrophy in our patient causing permanent vision loss.
Although we do not have any conclusive evidence that suggests iron overload as the cause for the purplish hue and bull's eye appearance of the macula, we do believe this discoloration could be due to ferritin accumulation.
We feel it is important to consider raised serum ferritin as a possible cause for vision loss as correcting this can prevent further visual loss.
Conclusion
Although bull's eye maculopathy in children and young adults points to a diagnosis of hereditary degenerations in most cases, a careful examination of the pattern of bull's eye in the macula and history-taking is essential. In this case, the outer zone of the bull's eye has a classic purple hue with a central bronze zone. A careful systemic history and history of drug intake are necessary. Although oral chelators may be harmful to the RPE, it is important to note that persistently raised serum ferritin may be more harmful.
The author has no financial/conflicting interests to disclose. | DEFERASIROX | DrugsGivenReaction | CC BY-NC-ND | 30395118 | 20,230,551 | 2021-07-01 |
What was the administration route of drug 'DEFERASIROX'? | BULL'S EYE MACULOPATHY POSSIBLY DUE TO IRON OVERLOAD IN A CHILD WITH THALASSEMIA MAJOR: A CASE OF POSSIBLE "FERRITIN RETINOPATHY".
OBJECTIVE
To report a case of bull's eye maculopathy probably caused by iron overload in a child with thalassemia major.
METHODS
Case report.
RESULTS
A 6-year-old girl with thalassemia major who was on chronic multiple blood transfusions since 2 years of age presented with blurred vision in both eyes for 2 months. Blood reports showed very high serum ferritin levels in the range 400 to 2,250 ng/mL (checked every 3 months) since 4 years of age. She was on oral iron chelator deferasirox for 2 years, which was stopped a month ago. Fundus examination of both eyes showed a characteristic bull's eye macula with a purplish hue in the outer ring probably due to iron deposition. The center of the bull's eye had a beaten bronze appearance.
CONCLUSIONS
Careful history-taking is important in children with bull's eye maculopathy because all such retinopathies need not be hereditary fundus dystrophies. Further progression can be arrested by identifying and removing the cause vision loss.
Bull's eye maculopathy is a term given to describe the appearance of the macula as a target or bull's eye. Degeneration of the retinal pigment epithelium (RPE) in the macular area causes alternating ring-like light and dark zones of pigmentation. This is the first case described to the best of our knowledge of bull's eye maculopathy probably caused due to serum iron overload in a child with thalassemia major.
Case Report
A 6-year-old girl of Indian origin, diagnosed to have beta thalassemia major at birth, presented with gradual decrease in vision in both eyes, especially for distance since 2 months. She had undergone multiple blood transfusions, and on repeated testing, her serum ferritin levels were between 400 ng/mL and 2,250 ng/mL checked every 3 months (normal range 7–140 ng/mL). She was using oral iron chelators deferasirox at 125 mg/day for 2 years, which was stopped a month back. Serum ferritin levels did not reach normal despite oral chelators.
On examination, best-corrected visual acuity was 20/100, N18 in the right eye and 20/40p, N8 in the left eye. Anterior segment examination was unremarkable. Fundus examination of both eyes showed a bull's eye pattern in the macula with a ring of purplish hue outside a circular bronze-colored zone of possible RPE atrophy (Figures 1 and 2). Optical coherence tomography of both eyes showed foveal thinning, more in the right eye, photoreceptor atrophy, and increased RPE reflectivity (Figures 3 and 4). Electroretinography showed extinguished photopic response while scotopic response was minimally affected.
Fig. 1. Fundus image of the right eye showing a purple-colored bull's eye maculopathy.
Fig. 2. Fundus image of the left eye showing a purple-colored bull's eye maculopathy.
Fig. 3. Optical coherence tomography of the right eye showing foveal and photoreceptor atrophy with underlying hyperreflectivity of the retinal pigment epithelium.
Fig. 4. Optical coherence tomography of the left eye showing foveal thinning with underlying hyperreflectivity of the RPE.
There was no history of family members affected with hereditary fundus dystrophies.
Discussion
Common causes of bull's eye maculopathy are progressive cone dystrophy, rod cone dystrophy, Stargardt dystrophy, benign concentric macular dystrophy, Batten disease, and drug-induced toxicity as in chloroquine and hydroxychloroquine retinopathy. In cone dystrophy, it is common to see a drop in visual acuity much earlier than fundus changes. Photophobia and loss of color vision are evident. With advancing age, visual acuity drops further with marked RPE atrophy in the fovea and temporal disk pallor. A bull's eye maculopathy in cone dystrophy presents as a lighter ring of RPE atrophy surrounding a dark center. In rod cone dystrophy, increased disk pallor, arteriolar attenuation, and pigmentary changes are seen in the retinal periphery, giving an appearance similar to that of retinitis pigmentosa. Night blindness occurs early in life. In Stargardt dystrophy, a beaten bronze–appearing fovea is seen with surrounding lighter RPE changes. This condition presents later in life and is rare in early childhood. Drug-induced toxicity is known to cause acquired bull's eye maculopathy.
β-Thalassemia major is a hereditary haemolytic anemia that is treated with multiple blood transfusions.1 In this condition, blood transfusions, ineffective erythropoiesis, and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload can be determined by serum ferritin measurement. In these patients, iron deposition in parenchymal tissues begins within 1 year of starting the regular transfusions.2
Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload because humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. A unit of erythrocytes transfused contains approximately 250 mg of iron, while the body cannot excrete more than 1 mg of iron per day. As iron loading progresses, the capacity of serum transferrin, the main transport protein of iron, to bind and detoxify iron may be exceeded. Thereafter, the non–transferrin-bound fraction of iron within plasma may promote generation of free hydroxyl radicals, propagators of oxygen-related damage.
Excess iron is extremely toxic to all cells of the body and can cause serious and irreversible organic damage, such as cirrhosis, diabetes, heart disease, and hypogonadism.3 Normal values of serum ferritin for men and women are 12 to 300 ng/mL and 12 to 150 ng/mL, respectively. The distribution of iron and ferritin has been characterized in the adult rat retina.3 Proton-induced X-ray emission identified the largest amounts of heme and nonheme iron in the inner segments of photoreceptors, the RPE, the choroid, the inner nuclear layer, and the ganglion cell layer. Iron was present in somewhat lesser, but still significant amounts in the photoreceptor outer segments. Interestingly, immunohistochemistry studies have demonstrated a similar distribution pattern of retinal ferritin. The exception is that iron, but not much ferritin, is contained in the photoreceptor outer segment.
Iron has an affinity for melanin in the RPE.4 Accumulation of iron in the RPE causes RPE atrophy and hence foveal and photoreceptor atrophy. The purplish hue in the outer ring of the bull's eye maculopathy seen in this child could possibly be due to iron accumulation. The center shows foveal atrophy, suggesting a loss of RPE due to previous iron accumulation.
Our patient was using oral chelator deferasirox at a dose of 125 mg/day for 2 years before she presented to us. This drug is known to cause reversible retinopathy and improvement of vision on drug withdrawal.5 This drug did not help lower the ferritin levels, which were persistently high for 2 years. Our patient had stopped oral chelators a month ago and yet noticed progressive loss of vision in both eyes. Optical coherence tomography showed foveal and photoreceptor atrophy in our patient causing permanent vision loss.
Although we do not have any conclusive evidence that suggests iron overload as the cause for the purplish hue and bull's eye appearance of the macula, we do believe this discoloration could be due to ferritin accumulation.
We feel it is important to consider raised serum ferritin as a possible cause for vision loss as correcting this can prevent further visual loss.
Conclusion
Although bull's eye maculopathy in children and young adults points to a diagnosis of hereditary degenerations in most cases, a careful examination of the pattern of bull's eye in the macula and history-taking is essential. In this case, the outer zone of the bull's eye has a classic purple hue with a central bronze zone. A careful systemic history and history of drug intake are necessary. Although oral chelators may be harmful to the RPE, it is important to note that persistently raised serum ferritin may be more harmful.
The author has no financial/conflicting interests to disclose. | Oral | DrugAdministrationRoute | CC BY-NC-ND | 30395118 | 19,834,466 | 2021-07-01 |
What was the outcome of reaction 'Maculopathy'? | BULL'S EYE MACULOPATHY POSSIBLY DUE TO IRON OVERLOAD IN A CHILD WITH THALASSEMIA MAJOR: A CASE OF POSSIBLE "FERRITIN RETINOPATHY".
OBJECTIVE
To report a case of bull's eye maculopathy probably caused by iron overload in a child with thalassemia major.
METHODS
Case report.
RESULTS
A 6-year-old girl with thalassemia major who was on chronic multiple blood transfusions since 2 years of age presented with blurred vision in both eyes for 2 months. Blood reports showed very high serum ferritin levels in the range 400 to 2,250 ng/mL (checked every 3 months) since 4 years of age. She was on oral iron chelator deferasirox for 2 years, which was stopped a month ago. Fundus examination of both eyes showed a characteristic bull's eye macula with a purplish hue in the outer ring probably due to iron deposition. The center of the bull's eye had a beaten bronze appearance.
CONCLUSIONS
Careful history-taking is important in children with bull's eye maculopathy because all such retinopathies need not be hereditary fundus dystrophies. Further progression can be arrested by identifying and removing the cause vision loss.
Bull's eye maculopathy is a term given to describe the appearance of the macula as a target or bull's eye. Degeneration of the retinal pigment epithelium (RPE) in the macular area causes alternating ring-like light and dark zones of pigmentation. This is the first case described to the best of our knowledge of bull's eye maculopathy probably caused due to serum iron overload in a child with thalassemia major.
Case Report
A 6-year-old girl of Indian origin, diagnosed to have beta thalassemia major at birth, presented with gradual decrease in vision in both eyes, especially for distance since 2 months. She had undergone multiple blood transfusions, and on repeated testing, her serum ferritin levels were between 400 ng/mL and 2,250 ng/mL checked every 3 months (normal range 7–140 ng/mL). She was using oral iron chelators deferasirox at 125 mg/day for 2 years, which was stopped a month back. Serum ferritin levels did not reach normal despite oral chelators.
On examination, best-corrected visual acuity was 20/100, N18 in the right eye and 20/40p, N8 in the left eye. Anterior segment examination was unremarkable. Fundus examination of both eyes showed a bull's eye pattern in the macula with a ring of purplish hue outside a circular bronze-colored zone of possible RPE atrophy (Figures 1 and 2). Optical coherence tomography of both eyes showed foveal thinning, more in the right eye, photoreceptor atrophy, and increased RPE reflectivity (Figures 3 and 4). Electroretinography showed extinguished photopic response while scotopic response was minimally affected.
Fig. 1. Fundus image of the right eye showing a purple-colored bull's eye maculopathy.
Fig. 2. Fundus image of the left eye showing a purple-colored bull's eye maculopathy.
Fig. 3. Optical coherence tomography of the right eye showing foveal and photoreceptor atrophy with underlying hyperreflectivity of the retinal pigment epithelium.
Fig. 4. Optical coherence tomography of the left eye showing foveal thinning with underlying hyperreflectivity of the RPE.
There was no history of family members affected with hereditary fundus dystrophies.
Discussion
Common causes of bull's eye maculopathy are progressive cone dystrophy, rod cone dystrophy, Stargardt dystrophy, benign concentric macular dystrophy, Batten disease, and drug-induced toxicity as in chloroquine and hydroxychloroquine retinopathy. In cone dystrophy, it is common to see a drop in visual acuity much earlier than fundus changes. Photophobia and loss of color vision are evident. With advancing age, visual acuity drops further with marked RPE atrophy in the fovea and temporal disk pallor. A bull's eye maculopathy in cone dystrophy presents as a lighter ring of RPE atrophy surrounding a dark center. In rod cone dystrophy, increased disk pallor, arteriolar attenuation, and pigmentary changes are seen in the retinal periphery, giving an appearance similar to that of retinitis pigmentosa. Night blindness occurs early in life. In Stargardt dystrophy, a beaten bronze–appearing fovea is seen with surrounding lighter RPE changes. This condition presents later in life and is rare in early childhood. Drug-induced toxicity is known to cause acquired bull's eye maculopathy.
β-Thalassemia major is a hereditary haemolytic anemia that is treated with multiple blood transfusions.1 In this condition, blood transfusions, ineffective erythropoiesis, and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload can be determined by serum ferritin measurement. In these patients, iron deposition in parenchymal tissues begins within 1 year of starting the regular transfusions.2
Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload because humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. A unit of erythrocytes transfused contains approximately 250 mg of iron, while the body cannot excrete more than 1 mg of iron per day. As iron loading progresses, the capacity of serum transferrin, the main transport protein of iron, to bind and detoxify iron may be exceeded. Thereafter, the non–transferrin-bound fraction of iron within plasma may promote generation of free hydroxyl radicals, propagators of oxygen-related damage.
Excess iron is extremely toxic to all cells of the body and can cause serious and irreversible organic damage, such as cirrhosis, diabetes, heart disease, and hypogonadism.3 Normal values of serum ferritin for men and women are 12 to 300 ng/mL and 12 to 150 ng/mL, respectively. The distribution of iron and ferritin has been characterized in the adult rat retina.3 Proton-induced X-ray emission identified the largest amounts of heme and nonheme iron in the inner segments of photoreceptors, the RPE, the choroid, the inner nuclear layer, and the ganglion cell layer. Iron was present in somewhat lesser, but still significant amounts in the photoreceptor outer segments. Interestingly, immunohistochemistry studies have demonstrated a similar distribution pattern of retinal ferritin. The exception is that iron, but not much ferritin, is contained in the photoreceptor outer segment.
Iron has an affinity for melanin in the RPE.4 Accumulation of iron in the RPE causes RPE atrophy and hence foveal and photoreceptor atrophy. The purplish hue in the outer ring of the bull's eye maculopathy seen in this child could possibly be due to iron accumulation. The center shows foveal atrophy, suggesting a loss of RPE due to previous iron accumulation.
Our patient was using oral chelator deferasirox at a dose of 125 mg/day for 2 years before she presented to us. This drug is known to cause reversible retinopathy and improvement of vision on drug withdrawal.5 This drug did not help lower the ferritin levels, which were persistently high for 2 years. Our patient had stopped oral chelators a month ago and yet noticed progressive loss of vision in both eyes. Optical coherence tomography showed foveal and photoreceptor atrophy in our patient causing permanent vision loss.
Although we do not have any conclusive evidence that suggests iron overload as the cause for the purplish hue and bull's eye appearance of the macula, we do believe this discoloration could be due to ferritin accumulation.
We feel it is important to consider raised serum ferritin as a possible cause for vision loss as correcting this can prevent further visual loss.
Conclusion
Although bull's eye maculopathy in children and young adults points to a diagnosis of hereditary degenerations in most cases, a careful examination of the pattern of bull's eye in the macula and history-taking is essential. In this case, the outer zone of the bull's eye has a classic purple hue with a central bronze zone. A careful systemic history and history of drug intake are necessary. Although oral chelators may be harmful to the RPE, it is important to note that persistently raised serum ferritin may be more harmful.
The author has no financial/conflicting interests to disclose. | Not recovered | ReactionOutcome | CC BY-NC-ND | 30395118 | 20,230,551 | 2021-07-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Idiopathic intracranial hypertension'. | CASE REPORT OF THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY IN RECOMBINANT GROWTH HORMONE THERAPY.
OBJECTIVE
To report the correlation between recombinant growth hormone (rhGH) dosage and retinal nerve fiber layer (RNFL) thickness values measured by optical coherence tomography in a case of pseudotumor cerebri syndrome (PTCS) after rhGH.
METHODS
An 11-year-old girl was receiving rhGH for panhypopituitarism. The patient developed PTCS, and her rhGH dose was adjusted using optical coherence tomography RNFL thickness measurements. The linear correlation coefficient (r) and coefficient of determination (r2) were calculated to assess the relationship between RNFL thickness and rhGH dose.
RESULTS
As the rhGH dosage was increased, the RNFL thickness values also increased, especially when acetazolamide was excluded because of its confounding effect. (r = 0.64) In separate subgroup analysis, a higher acetazolamide dosage strongly correlated with reduced RNFL thickness (r = 0.77).
CONCLUSIONS
Although PTCS is a rare complication after rhGH therapy, its detrimental effects cannot be ignored. In our case report, we used optical coherence tomography RNFL values in addition to clinical findings to carefully titrate the rhGH dosage to prevent a flare-up of PTCS. Despite the obvious need for larger studies, our case report shows the value of RNFL thickness measured by optical coherence tomography and the valuable additional data it provides to refine rhGH therapy as an adjunct noninvasive method in PTCS.
pmcPseudotumor cerebri syndrome (PTCS) after recombinant human growth hormone (rhGH) therapy is a rare but an important complication.1 Cessation of the therapy is often adequate for reversal of PTCS; however, this is complicated by the growth requirements of the patient.1 To the best of our knowledge, we report the first case of the prevention of flare-up of PTCS by titrating the rhGH dose based on retinal nerve fiber layer (RNFL) thickness values obtained by optical coherence tomography (OCT).
Case Report
An 11-year-old girl with a history of panhypopituitarism had been followed-up by the pediatric endocrinology (PE) team at University Hospitals Cleveland Medical Center since birth. She was referred to pediatric ophthalmology due to intermittent occipital headaches. A full ophthalmic examination was unremarkable except for the dilated fundus examination, which revealed +2 optic disc edema (ODE) in both eyes (Figure 1). The results of OCT of the optic discs revealed increased RNFL thickness in both eyes (Figure 2).
Fig. 1. Fundus photography of the patient at the first visit revealing bilateral ODEs.
Fig. 2. Optical coherence tomography RNFL changes. On November 13, 2013, the patient was receiving a 0.8 mg/kg rhGH dose, and her OCT RNFL values were greatly increased. Fifteen days later, upon stopping rhGH therapy totally, the OCT RNFL values started decreasing, and after 2 months, the values returned to normal.
Magnetic resonance imaging showed pituitary hypoplasia in 2007, and treatment with hydrocortisone, levothyroxine, and somatropin (rhGH) was started. Other examinations were otherwise normal. The patient was born at 39 weeks of gestation with a birth weight of 3,517 g. No apparent reason was found for her hypopituitarism.
Recombinant human growth hormone was stopped immediately, and magnetic resonance imaging and lumbar puncture were ordered to rule out PTCS. Visual acuity for both eyes was still 20/15, and ODE improved in the next follow-up after 2 weeks (Figure 2). Magnetic resonance imaging was negative, and lumbar puncture revealed high opening pressures, leading to confirmation of PTCS. Recombinant human growth hormone was started again, albeit on a lower dose at 0.3 mg/day reduced from 0.8 mg/day, and no ODE was noted in the next 2 months (Figure 2).
However, the patient's growth rate halted because of inefficient rhGH. After communication among the medical providers, the rhGH dose was increased from 0.3 mg/day to 0.5 mg/day. Three-month follow-up revealed mild ODE, which was confirmed with increased RNFL OCT values (Figure 3A). After consultations with the PE team, the rhGH dose was reduced to 0.3 mg/day again. Dilated fundus examination revealed improved ODE, which was confirmed with RNFL OCT values (Figure 3B). To increase the growth rate further, the PE team decided to increase the rhGH dose to 0.8 mg/day incrementally. Subsequent visits revealed normal optic discs and stable OCT values up to 0.7 mg/day. However, after 3 months on 0.7 mg/day, OCT RNFL values increased, and the dose was adjusted to 0.4 mg/day (Figure 3C). In addition to decreasing the dose of rhGH, 250 mg/day acetazolamide was started. At the 2-month follow-up, OCT RNFL values returned to baseline (Figure 3D). The PE team again began to incrementally increase the dose to 0.8 mg/day. Two months later, OCT RNFL values again increased above baseline despite the acetazolamide therapy (Figure 4A). A second lumbar puncture revealed high opening pressures. However, because of the slow growth rate, declining percentiles, and episodes of hypoglycemia, rhGH was not stopped completely but was instead reduced to 0.4 mg/day with 250 mg acetazolamide. Optical coherence tomography RNFL values were then the same as those at baseline (Figure 4B). As the PE team was not satisfied with the growth rate, the dose was increased to 0.8 mg/day. Clinical examination showed mildly elevated optic nerve head with elevated RNFL values (Figure 4C). We decided to increase the acetazolamide dose to 500 mg without changing the dose of rhGH. At her next visit, the patient had slightly lower RNFL values, but they had not returned to baseline (Figure 4D). Therefore, we decided to further increase the acetazolamide dose to 750 mg. At the next visit, the PE team reported that the patient's growth had reached a normal rate but requested to further increase the dose. Subsequent visits showed the RNFL values returning to baseline with 750 mg acetazolamide; therefore, the rhGH dosage was increased to 0.9 mg/day (Figure 5).
Fig. 3. A. OCT RNFL values with 0.5 mg/day rhGH. B. OCT RNFL values after decreasing the rhGH dose to 0.3 mg/dL. C. OCT RNFL values after increasing the rhGH dose to 0.7 mg/dL. D. OCT RNFL values after decreasing the rhGH dose to 0.4 mg/dL and starting 250 mg acetazolamide.
Fig. 4. A. OCT RNFL values after rhGH was increased to 0.8 mg/dL with 250 mg acetazolamide. B. OCT RNFL values after rhGH was reduced to 0.4 mg/dL with 250 mg acetazolamide. C. OCT RNFL values after increasing the rhGH dose to 0.8 mg/dL. D. OCT RNFL values after increasing acetazolamide to 500 mg.
Fig. 5. OCT RNFL values after increasing acetazolamide to 750 mg.
Methods and Results
The rhGH dose values were compared against the RNFL thickness values, and the Pearson's product moment correlation coefficient for sample statistic (r) and coefficient of determination (r2) were calculated to assess the relationship using Microsoft Excel. (Microsoft, Redmond, WA) We performed three different analyses to explore the relationship between the RNFL and rhGH dosage in this single-patient case study. In the first analysis, we looked at the relationship between all RNFL values and rhGH dosage. The correlation between average RNFL values and its relationship with rhGH dosage were relatively weak (r = 0.47 and r2 = 0.22) (Figure 6A). Calculating each quadrant separately also showed a relatively low correlation (Figure 6, B–E). In the second analysis, we removed the RNFL values under acetazolamide treatment and only compared nontreated RNFL values against the rhGH dosage. This time, the correlation for both the average values and quadrants separately was much higher (r = 0.64, r2 = 0.40) (Figure 7). For the third analysis, we only calculated acetazolamide's effect on RNFL under 0.8 mg/mL rhGH, which revealed a high negative correlation. Higher doses of the drug correlated strongly with lower (i.e., thinner) RNFL values (r = 0.77, r2 = 0.59) (Figure 8).
Fig. 6. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. Despite an overall positive correlation between rhGH dose and RNFL thickness was observed, it was not very strong (r = 0.47, r2 = 0.22). B–E. Superior, inferior, nasal, and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. When the correlation was recalculated for each quadrant separately, the overall trend of positive but weak correlation between rhGH dose and RNFL thickness persisted.
Fig. 7. Acetazolamide exclusion subgroup analysis. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. Removing RNFL values under acetazolamide treated further strengthened the positive correlation between rhGH dose and RNFL thickness (r = 0.64, r2 = 0.40). B–E. Superior, inferior, nasal and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. When the correlation was recalculated for each quadrant separately, the strengthened positive trend persisted with exception of the temporal quadrant.
Fig. 8. Average RNFL values at 0.8 mg/dL with different acetazolamide doses, correlation graph with coefficient of correlation and determination values. Higher doses of acetazolamide resulted lower (i.e., thinner) RNFL values, indicating a very strong negative correlation (r = 0.77, r2 = 0.59).
Discussion
In recent years, OCT has started to be used in neuro-ophthalmology practices, especially for the follow-up of ODE.2 In a multicenter trial by the NORDIC Idiopathic Intracranial Hypertension Study Group, the OCT substudy committee showed that idiopathic intracranial hypertension therapy with acetazolamide and weight loss effectively improved RNFL thickness values.3 In part II of the study, the OCT measurements were shown to strongly correlate with the Frisen grading of papilledema.4
Although rhGH therapy is relatively safe and is associated with only few adverse effects,5 it is essential to perform ophthalmic examination to detect PTCS and its detrimental effects on the eye.5 In children, PTCS can be entirely asymptomatic and in early stages may present only with subtle papilledema.6 When diagnosed at relatively later stages, studies have shown permanent loss of vision and visual field defects in up to 10% and 17% of children, respectively.6 The pathogenesis of rhGH-induced PTCS remains relatively unknown. It is postulated to alter cerebrospinal fluid drainage across arachnoid villi.6 It is also theorized that rhGH might be increasing cerebrospinal fluid production by the way of IGF-1 receptors.7 Ophthalmoscopic examination of the fundus has been the gold standard for optic nerve evaluations.3 However, this technique is limited because assessment is subjective and based on the training and experience of the physician, especially for subtle changes. A noninvasive adjunct evaluation tool, such as OCT, might therefore be valuable in the evaluation and follow-up of patients, especially children.
To the best of our knowledge, this is the first report in the literature that correlates OCT RNFL values with rhGH dose. As mentioned previously, there is a substantial amount of information in the literature showing the relationship between rhGH therapy and PTCS.5,6 The literature also shows that OCT is reliable for the follow-up of PTCS and related papilledema.2–4 Our case report combines these two pieces of information from the literature.
We have found that the average RNFL values correlated well with rhGH, especially when acetazolamide's effect was not included in the calculations. When we studied each quadrant separately, all had a good correlation of RNFL values with rhGH dose. The correlation was higher in the superior and inferior quadrants compared with the nasal and temporal quadrants. This finding was consistent in both the general and acetazolamide exclusion groups. As reported in previous studies, we also found that higher doses of acetazolamide correlated with lower (thinner) RNFL values.3
Optical coherence tomography was used to measure RNFL thickness every 2 months or at each rhGH dose adjustment. In the case of PTCS after rhGH therapy, rhGH is usually stopped all together until resolution and restarted at a lower dose.5 By contrast, we were able to titrate the dose precisely to prevent a flare-up of PTCS but without stopping it totally. The OCT was easy to use and accurately demonstrated even minor changes in the RNFL thickness.
In our case report, we observed a correlation between rhGH dose and RNFL thickness measured by OCT, especially when acetazolamide was excluded because of its confounding effect. If it can be verified in larger prospective and randomized trials, this finding could be an early sign of rhGH-induced PTCS. Early detection and careful management of patients who receive rhGH might be a preventative measure.
The study was presented as a poster presentation in Research ShowCASE meeting at Case Western Reserve University, Cleveland, OH, 2016.
None of the authors has any financial/conflicting interests to disclose. | HYDROCORTISONE, LEVOTHYROXINE, SOMATROPIN | DrugsGivenReaction | CC BY-NC-ND | 31568222 | 20,266,280 | 2021-11-01 |
Give an alphabetized list of all active substances of drugs taken by the patient who experienced 'Product use in unapproved indication'. | CASE REPORT OF THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY IN RECOMBINANT GROWTH HORMONE THERAPY.
OBJECTIVE
To report the correlation between recombinant growth hormone (rhGH) dosage and retinal nerve fiber layer (RNFL) thickness values measured by optical coherence tomography in a case of pseudotumor cerebri syndrome (PTCS) after rhGH.
METHODS
An 11-year-old girl was receiving rhGH for panhypopituitarism. The patient developed PTCS, and her rhGH dose was adjusted using optical coherence tomography RNFL thickness measurements. The linear correlation coefficient (r) and coefficient of determination (r2) were calculated to assess the relationship between RNFL thickness and rhGH dose.
RESULTS
As the rhGH dosage was increased, the RNFL thickness values also increased, especially when acetazolamide was excluded because of its confounding effect. (r = 0.64) In separate subgroup analysis, a higher acetazolamide dosage strongly correlated with reduced RNFL thickness (r = 0.77).
CONCLUSIONS
Although PTCS is a rare complication after rhGH therapy, its detrimental effects cannot be ignored. In our case report, we used optical coherence tomography RNFL values in addition to clinical findings to carefully titrate the rhGH dosage to prevent a flare-up of PTCS. Despite the obvious need for larger studies, our case report shows the value of RNFL thickness measured by optical coherence tomography and the valuable additional data it provides to refine rhGH therapy as an adjunct noninvasive method in PTCS.
pmcPseudotumor cerebri syndrome (PTCS) after recombinant human growth hormone (rhGH) therapy is a rare but an important complication.1 Cessation of the therapy is often adequate for reversal of PTCS; however, this is complicated by the growth requirements of the patient.1 To the best of our knowledge, we report the first case of the prevention of flare-up of PTCS by titrating the rhGH dose based on retinal nerve fiber layer (RNFL) thickness values obtained by optical coherence tomography (OCT).
Case Report
An 11-year-old girl with a history of panhypopituitarism had been followed-up by the pediatric endocrinology (PE) team at University Hospitals Cleveland Medical Center since birth. She was referred to pediatric ophthalmology due to intermittent occipital headaches. A full ophthalmic examination was unremarkable except for the dilated fundus examination, which revealed +2 optic disc edema (ODE) in both eyes (Figure 1). The results of OCT of the optic discs revealed increased RNFL thickness in both eyes (Figure 2).
Fig. 1. Fundus photography of the patient at the first visit revealing bilateral ODEs.
Fig. 2. Optical coherence tomography RNFL changes. On November 13, 2013, the patient was receiving a 0.8 mg/kg rhGH dose, and her OCT RNFL values were greatly increased. Fifteen days later, upon stopping rhGH therapy totally, the OCT RNFL values started decreasing, and after 2 months, the values returned to normal.
Magnetic resonance imaging showed pituitary hypoplasia in 2007, and treatment with hydrocortisone, levothyroxine, and somatropin (rhGH) was started. Other examinations were otherwise normal. The patient was born at 39 weeks of gestation with a birth weight of 3,517 g. No apparent reason was found for her hypopituitarism.
Recombinant human growth hormone was stopped immediately, and magnetic resonance imaging and lumbar puncture were ordered to rule out PTCS. Visual acuity for both eyes was still 20/15, and ODE improved in the next follow-up after 2 weeks (Figure 2). Magnetic resonance imaging was negative, and lumbar puncture revealed high opening pressures, leading to confirmation of PTCS. Recombinant human growth hormone was started again, albeit on a lower dose at 0.3 mg/day reduced from 0.8 mg/day, and no ODE was noted in the next 2 months (Figure 2).
However, the patient's growth rate halted because of inefficient rhGH. After communication among the medical providers, the rhGH dose was increased from 0.3 mg/day to 0.5 mg/day. Three-month follow-up revealed mild ODE, which was confirmed with increased RNFL OCT values (Figure 3A). After consultations with the PE team, the rhGH dose was reduced to 0.3 mg/day again. Dilated fundus examination revealed improved ODE, which was confirmed with RNFL OCT values (Figure 3B). To increase the growth rate further, the PE team decided to increase the rhGH dose to 0.8 mg/day incrementally. Subsequent visits revealed normal optic discs and stable OCT values up to 0.7 mg/day. However, after 3 months on 0.7 mg/day, OCT RNFL values increased, and the dose was adjusted to 0.4 mg/day (Figure 3C). In addition to decreasing the dose of rhGH, 250 mg/day acetazolamide was started. At the 2-month follow-up, OCT RNFL values returned to baseline (Figure 3D). The PE team again began to incrementally increase the dose to 0.8 mg/day. Two months later, OCT RNFL values again increased above baseline despite the acetazolamide therapy (Figure 4A). A second lumbar puncture revealed high opening pressures. However, because of the slow growth rate, declining percentiles, and episodes of hypoglycemia, rhGH was not stopped completely but was instead reduced to 0.4 mg/day with 250 mg acetazolamide. Optical coherence tomography RNFL values were then the same as those at baseline (Figure 4B). As the PE team was not satisfied with the growth rate, the dose was increased to 0.8 mg/day. Clinical examination showed mildly elevated optic nerve head with elevated RNFL values (Figure 4C). We decided to increase the acetazolamide dose to 500 mg without changing the dose of rhGH. At her next visit, the patient had slightly lower RNFL values, but they had not returned to baseline (Figure 4D). Therefore, we decided to further increase the acetazolamide dose to 750 mg. At the next visit, the PE team reported that the patient's growth had reached a normal rate but requested to further increase the dose. Subsequent visits showed the RNFL values returning to baseline with 750 mg acetazolamide; therefore, the rhGH dosage was increased to 0.9 mg/day (Figure 5).
Fig. 3. A. OCT RNFL values with 0.5 mg/day rhGH. B. OCT RNFL values after decreasing the rhGH dose to 0.3 mg/dL. C. OCT RNFL values after increasing the rhGH dose to 0.7 mg/dL. D. OCT RNFL values after decreasing the rhGH dose to 0.4 mg/dL and starting 250 mg acetazolamide.
Fig. 4. A. OCT RNFL values after rhGH was increased to 0.8 mg/dL with 250 mg acetazolamide. B. OCT RNFL values after rhGH was reduced to 0.4 mg/dL with 250 mg acetazolamide. C. OCT RNFL values after increasing the rhGH dose to 0.8 mg/dL. D. OCT RNFL values after increasing acetazolamide to 500 mg.
Fig. 5. OCT RNFL values after increasing acetazolamide to 750 mg.
Methods and Results
The rhGH dose values were compared against the RNFL thickness values, and the Pearson's product moment correlation coefficient for sample statistic (r) and coefficient of determination (r2) were calculated to assess the relationship using Microsoft Excel. (Microsoft, Redmond, WA) We performed three different analyses to explore the relationship between the RNFL and rhGH dosage in this single-patient case study. In the first analysis, we looked at the relationship between all RNFL values and rhGH dosage. The correlation between average RNFL values and its relationship with rhGH dosage were relatively weak (r = 0.47 and r2 = 0.22) (Figure 6A). Calculating each quadrant separately also showed a relatively low correlation (Figure 6, B–E). In the second analysis, we removed the RNFL values under acetazolamide treatment and only compared nontreated RNFL values against the rhGH dosage. This time, the correlation for both the average values and quadrants separately was much higher (r = 0.64, r2 = 0.40) (Figure 7). For the third analysis, we only calculated acetazolamide's effect on RNFL under 0.8 mg/mL rhGH, which revealed a high negative correlation. Higher doses of the drug correlated strongly with lower (i.e., thinner) RNFL values (r = 0.77, r2 = 0.59) (Figure 8).
Fig. 6. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. Despite an overall positive correlation between rhGH dose and RNFL thickness was observed, it was not very strong (r = 0.47, r2 = 0.22). B–E. Superior, inferior, nasal, and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. When the correlation was recalculated for each quadrant separately, the overall trend of positive but weak correlation between rhGH dose and RNFL thickness persisted.
Fig. 7. Acetazolamide exclusion subgroup analysis. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. Removing RNFL values under acetazolamide treated further strengthened the positive correlation between rhGH dose and RNFL thickness (r = 0.64, r2 = 0.40). B–E. Superior, inferior, nasal and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. When the correlation was recalculated for each quadrant separately, the strengthened positive trend persisted with exception of the temporal quadrant.
Fig. 8. Average RNFL values at 0.8 mg/dL with different acetazolamide doses, correlation graph with coefficient of correlation and determination values. Higher doses of acetazolamide resulted lower (i.e., thinner) RNFL values, indicating a very strong negative correlation (r = 0.77, r2 = 0.59).
Discussion
In recent years, OCT has started to be used in neuro-ophthalmology practices, especially for the follow-up of ODE.2 In a multicenter trial by the NORDIC Idiopathic Intracranial Hypertension Study Group, the OCT substudy committee showed that idiopathic intracranial hypertension therapy with acetazolamide and weight loss effectively improved RNFL thickness values.3 In part II of the study, the OCT measurements were shown to strongly correlate with the Frisen grading of papilledema.4
Although rhGH therapy is relatively safe and is associated with only few adverse effects,5 it is essential to perform ophthalmic examination to detect PTCS and its detrimental effects on the eye.5 In children, PTCS can be entirely asymptomatic and in early stages may present only with subtle papilledema.6 When diagnosed at relatively later stages, studies have shown permanent loss of vision and visual field defects in up to 10% and 17% of children, respectively.6 The pathogenesis of rhGH-induced PTCS remains relatively unknown. It is postulated to alter cerebrospinal fluid drainage across arachnoid villi.6 It is also theorized that rhGH might be increasing cerebrospinal fluid production by the way of IGF-1 receptors.7 Ophthalmoscopic examination of the fundus has been the gold standard for optic nerve evaluations.3 However, this technique is limited because assessment is subjective and based on the training and experience of the physician, especially for subtle changes. A noninvasive adjunct evaluation tool, such as OCT, might therefore be valuable in the evaluation and follow-up of patients, especially children.
To the best of our knowledge, this is the first report in the literature that correlates OCT RNFL values with rhGH dose. As mentioned previously, there is a substantial amount of information in the literature showing the relationship between rhGH therapy and PTCS.5,6 The literature also shows that OCT is reliable for the follow-up of PTCS and related papilledema.2–4 Our case report combines these two pieces of information from the literature.
We have found that the average RNFL values correlated well with rhGH, especially when acetazolamide's effect was not included in the calculations. When we studied each quadrant separately, all had a good correlation of RNFL values with rhGH dose. The correlation was higher in the superior and inferior quadrants compared with the nasal and temporal quadrants. This finding was consistent in both the general and acetazolamide exclusion groups. As reported in previous studies, we also found that higher doses of acetazolamide correlated with lower (thinner) RNFL values.3
Optical coherence tomography was used to measure RNFL thickness every 2 months or at each rhGH dose adjustment. In the case of PTCS after rhGH therapy, rhGH is usually stopped all together until resolution and restarted at a lower dose.5 By contrast, we were able to titrate the dose precisely to prevent a flare-up of PTCS but without stopping it totally. The OCT was easy to use and accurately demonstrated even minor changes in the RNFL thickness.
In our case report, we observed a correlation between rhGH dose and RNFL thickness measured by OCT, especially when acetazolamide was excluded because of its confounding effect. If it can be verified in larger prospective and randomized trials, this finding could be an early sign of rhGH-induced PTCS. Early detection and careful management of patients who receive rhGH might be a preventative measure.
The study was presented as a poster presentation in Research ShowCASE meeting at Case Western Reserve University, Cleveland, OH, 2016.
None of the authors has any financial/conflicting interests to disclose. | HYDROCORTISONE, LEVOTHYROXINE, SOMATROPIN | DrugsGivenReaction | CC BY-NC-ND | 31568222 | 20,266,280 | 2021-11-01 |
What was the dosage of drug 'HYDROCORTISONE'? | CASE REPORT OF THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY IN RECOMBINANT GROWTH HORMONE THERAPY.
OBJECTIVE
To report the correlation between recombinant growth hormone (rhGH) dosage and retinal nerve fiber layer (RNFL) thickness values measured by optical coherence tomography in a case of pseudotumor cerebri syndrome (PTCS) after rhGH.
METHODS
An 11-year-old girl was receiving rhGH for panhypopituitarism. The patient developed PTCS, and her rhGH dose was adjusted using optical coherence tomography RNFL thickness measurements. The linear correlation coefficient (r) and coefficient of determination (r2) were calculated to assess the relationship between RNFL thickness and rhGH dose.
RESULTS
As the rhGH dosage was increased, the RNFL thickness values also increased, especially when acetazolamide was excluded because of its confounding effect. (r = 0.64) In separate subgroup analysis, a higher acetazolamide dosage strongly correlated with reduced RNFL thickness (r = 0.77).
CONCLUSIONS
Although PTCS is a rare complication after rhGH therapy, its detrimental effects cannot be ignored. In our case report, we used optical coherence tomography RNFL values in addition to clinical findings to carefully titrate the rhGH dosage to prevent a flare-up of PTCS. Despite the obvious need for larger studies, our case report shows the value of RNFL thickness measured by optical coherence tomography and the valuable additional data it provides to refine rhGH therapy as an adjunct noninvasive method in PTCS.
pmcPseudotumor cerebri syndrome (PTCS) after recombinant human growth hormone (rhGH) therapy is a rare but an important complication.1 Cessation of the therapy is often adequate for reversal of PTCS; however, this is complicated by the growth requirements of the patient.1 To the best of our knowledge, we report the first case of the prevention of flare-up of PTCS by titrating the rhGH dose based on retinal nerve fiber layer (RNFL) thickness values obtained by optical coherence tomography (OCT).
Case Report
An 11-year-old girl with a history of panhypopituitarism had been followed-up by the pediatric endocrinology (PE) team at University Hospitals Cleveland Medical Center since birth. She was referred to pediatric ophthalmology due to intermittent occipital headaches. A full ophthalmic examination was unremarkable except for the dilated fundus examination, which revealed +2 optic disc edema (ODE) in both eyes (Figure 1). The results of OCT of the optic discs revealed increased RNFL thickness in both eyes (Figure 2).
Fig. 1. Fundus photography of the patient at the first visit revealing bilateral ODEs.
Fig. 2. Optical coherence tomography RNFL changes. On November 13, 2013, the patient was receiving a 0.8 mg/kg rhGH dose, and her OCT RNFL values were greatly increased. Fifteen days later, upon stopping rhGH therapy totally, the OCT RNFL values started decreasing, and after 2 months, the values returned to normal.
Magnetic resonance imaging showed pituitary hypoplasia in 2007, and treatment with hydrocortisone, levothyroxine, and somatropin (rhGH) was started. Other examinations were otherwise normal. The patient was born at 39 weeks of gestation with a birth weight of 3,517 g. No apparent reason was found for her hypopituitarism.
Recombinant human growth hormone was stopped immediately, and magnetic resonance imaging and lumbar puncture were ordered to rule out PTCS. Visual acuity for both eyes was still 20/15, and ODE improved in the next follow-up after 2 weeks (Figure 2). Magnetic resonance imaging was negative, and lumbar puncture revealed high opening pressures, leading to confirmation of PTCS. Recombinant human growth hormone was started again, albeit on a lower dose at 0.3 mg/day reduced from 0.8 mg/day, and no ODE was noted in the next 2 months (Figure 2).
However, the patient's growth rate halted because of inefficient rhGH. After communication among the medical providers, the rhGH dose was increased from 0.3 mg/day to 0.5 mg/day. Three-month follow-up revealed mild ODE, which was confirmed with increased RNFL OCT values (Figure 3A). After consultations with the PE team, the rhGH dose was reduced to 0.3 mg/day again. Dilated fundus examination revealed improved ODE, which was confirmed with RNFL OCT values (Figure 3B). To increase the growth rate further, the PE team decided to increase the rhGH dose to 0.8 mg/day incrementally. Subsequent visits revealed normal optic discs and stable OCT values up to 0.7 mg/day. However, after 3 months on 0.7 mg/day, OCT RNFL values increased, and the dose was adjusted to 0.4 mg/day (Figure 3C). In addition to decreasing the dose of rhGH, 250 mg/day acetazolamide was started. At the 2-month follow-up, OCT RNFL values returned to baseline (Figure 3D). The PE team again began to incrementally increase the dose to 0.8 mg/day. Two months later, OCT RNFL values again increased above baseline despite the acetazolamide therapy (Figure 4A). A second lumbar puncture revealed high opening pressures. However, because of the slow growth rate, declining percentiles, and episodes of hypoglycemia, rhGH was not stopped completely but was instead reduced to 0.4 mg/day with 250 mg acetazolamide. Optical coherence tomography RNFL values were then the same as those at baseline (Figure 4B). As the PE team was not satisfied with the growth rate, the dose was increased to 0.8 mg/day. Clinical examination showed mildly elevated optic nerve head with elevated RNFL values (Figure 4C). We decided to increase the acetazolamide dose to 500 mg without changing the dose of rhGH. At her next visit, the patient had slightly lower RNFL values, but they had not returned to baseline (Figure 4D). Therefore, we decided to further increase the acetazolamide dose to 750 mg. At the next visit, the PE team reported that the patient's growth had reached a normal rate but requested to further increase the dose. Subsequent visits showed the RNFL values returning to baseline with 750 mg acetazolamide; therefore, the rhGH dosage was increased to 0.9 mg/day (Figure 5).
Fig. 3. A. OCT RNFL values with 0.5 mg/day rhGH. B. OCT RNFL values after decreasing the rhGH dose to 0.3 mg/dL. C. OCT RNFL values after increasing the rhGH dose to 0.7 mg/dL. D. OCT RNFL values after decreasing the rhGH dose to 0.4 mg/dL and starting 250 mg acetazolamide.
Fig. 4. A. OCT RNFL values after rhGH was increased to 0.8 mg/dL with 250 mg acetazolamide. B. OCT RNFL values after rhGH was reduced to 0.4 mg/dL with 250 mg acetazolamide. C. OCT RNFL values after increasing the rhGH dose to 0.8 mg/dL. D. OCT RNFL values after increasing acetazolamide to 500 mg.
Fig. 5. OCT RNFL values after increasing acetazolamide to 750 mg.
Methods and Results
The rhGH dose values were compared against the RNFL thickness values, and the Pearson's product moment correlation coefficient for sample statistic (r) and coefficient of determination (r2) were calculated to assess the relationship using Microsoft Excel. (Microsoft, Redmond, WA) We performed three different analyses to explore the relationship between the RNFL and rhGH dosage in this single-patient case study. In the first analysis, we looked at the relationship between all RNFL values and rhGH dosage. The correlation between average RNFL values and its relationship with rhGH dosage were relatively weak (r = 0.47 and r2 = 0.22) (Figure 6A). Calculating each quadrant separately also showed a relatively low correlation (Figure 6, B–E). In the second analysis, we removed the RNFL values under acetazolamide treatment and only compared nontreated RNFL values against the rhGH dosage. This time, the correlation for both the average values and quadrants separately was much higher (r = 0.64, r2 = 0.40) (Figure 7). For the third analysis, we only calculated acetazolamide's effect on RNFL under 0.8 mg/mL rhGH, which revealed a high negative correlation. Higher doses of the drug correlated strongly with lower (i.e., thinner) RNFL values (r = 0.77, r2 = 0.59) (Figure 8).
Fig. 6. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. Despite an overall positive correlation between rhGH dose and RNFL thickness was observed, it was not very strong (r = 0.47, r2 = 0.22). B–E. Superior, inferior, nasal, and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values. When the correlation was recalculated for each quadrant separately, the overall trend of positive but weak correlation between rhGH dose and RNFL thickness persisted.
Fig. 7. Acetazolamide exclusion subgroup analysis. A. Average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. Removing RNFL values under acetazolamide treated further strengthened the positive correlation between rhGH dose and RNFL thickness (r = 0.64, r2 = 0.40). B–E. Superior, inferior, nasal and temporal quadrant average RNFL values at different rhGH dosages, correlation graph with coefficient of correlation and determination values after RNFL values under acetazolamide treatment were excluded. When the correlation was recalculated for each quadrant separately, the strengthened positive trend persisted with exception of the temporal quadrant.
Fig. 8. Average RNFL values at 0.8 mg/dL with different acetazolamide doses, correlation graph with coefficient of correlation and determination values. Higher doses of acetazolamide resulted lower (i.e., thinner) RNFL values, indicating a very strong negative correlation (r = 0.77, r2 = 0.59).
Discussion
In recent years, OCT has started to be used in neuro-ophthalmology practices, especially for the follow-up of ODE.2 In a multicenter trial by the NORDIC Idiopathic Intracranial Hypertension Study Group, the OCT substudy committee showed that idiopathic intracranial hypertension therapy with acetazolamide and weight loss effectively improved RNFL thickness values.3 In part II of the study, the OCT measurements were shown to strongly correlate with the Frisen grading of papilledema.4
Although rhGH therapy is relatively safe and is associated with only few adverse effects,5 it is essential to perform ophthalmic examination to detect PTCS and its detrimental effects on the eye.5 In children, PTCS can be entirely asymptomatic and in early stages may present only with subtle papilledema.6 When diagnosed at relatively later stages, studies have shown permanent loss of vision and visual field defects in up to 10% and 17% of children, respectively.6 The pathogenesis of rhGH-induced PTCS remains relatively unknown. It is postulated to alter cerebrospinal fluid drainage across arachnoid villi.6 It is also theorized that rhGH might be increasing cerebrospinal fluid production by the way of IGF-1 receptors.7 Ophthalmoscopic examination of the fundus has been the gold standard for optic nerve evaluations.3 However, this technique is limited because assessment is subjective and based on the training and experience of the physician, especially for subtle changes. A noninvasive adjunct evaluation tool, such as OCT, might therefore be valuable in the evaluation and follow-up of patients, especially children.
To the best of our knowledge, this is the first report in the literature that correlates OCT RNFL values with rhGH dose. As mentioned previously, there is a substantial amount of information in the literature showing the relationship between rhGH therapy and PTCS.5,6 The literature also shows that OCT is reliable for the follow-up of PTCS and related papilledema.2–4 Our case report combines these two pieces of information from the literature.
We have found that the average RNFL values correlated well with rhGH, especially when acetazolamide's effect was not included in the calculations. When we studied each quadrant separately, all had a good correlation of RNFL values with rhGH dose. The correlation was higher in the superior and inferior quadrants compared with the nasal and temporal quadrants. This finding was consistent in both the general and acetazolamide exclusion groups. As reported in previous studies, we also found that higher doses of acetazolamide correlated with lower (thinner) RNFL values.3
Optical coherence tomography was used to measure RNFL thickness every 2 months or at each rhGH dose adjustment. In the case of PTCS after rhGH therapy, rhGH is usually stopped all together until resolution and restarted at a lower dose.5 By contrast, we were able to titrate the dose precisely to prevent a flare-up of PTCS but without stopping it totally. The OCT was easy to use and accurately demonstrated even minor changes in the RNFL thickness.
In our case report, we observed a correlation between rhGH dose and RNFL thickness measured by OCT, especially when acetazolamide was excluded because of its confounding effect. If it can be verified in larger prospective and randomized trials, this finding could be an early sign of rhGH-induced PTCS. Early detection and careful management of patients who receive rhGH might be a preventative measure.
The study was presented as a poster presentation in Research ShowCASE meeting at Case Western Reserve University, Cleveland, OH, 2016.
None of the authors has any financial/conflicting interests to disclose. | UNK UNK, UNKNOWN | DrugDosageText | CC BY-NC-ND | 31568222 | 20,266,280 | 2021-11-01 |
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