Statin sensitive lipid-retinopathy in familial hypercholesterolemia

Aysha Salam; Prasad Palimar; Alison Davis

doi:10.4103/2320-3897.116850

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Year : 2013 | Volume : 1 | Issue : 3 | Page : 155-156

Statin sensitive lipid-retinopathy in familial hypercholesterolemia

Aysha Salam¹, Prasad Palimar¹, Alison Davis²
¹ Department of Ophthalmology, Warrington Hospital, Warrington, Cheshire WA5 1QG, United Kingdom
² Department of Pathology, Warrington Hospital, Warrington, Cheshire WA5 1QG, United Kingdom

Date of Submission	01-Mar-2013
Date of Acceptance	20-May-2013
Date of Web Publication	23-Aug-2013

Correspondence Address:
Prasad Palimar
Department of Ophthalmology, Warrington Hospital, Warrington, Cheshire WA5 1QG
United Kingdom

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2320-3897.116850

Abstract

An asymptomatic 9-year-old boy was referred for extensive lipid exudation into the retina. He was known to have familial hypercholesterolemia. The lipids resorbed rapidly and spontaneously merely by lowering the cholesterol levels with statins. The possible mechanism of action and the potential role of expanding this therapy are briefly discussed.

Keywords: Familial hypercholesterolemia, lipid retinopathy, statins

How to cite this article:
Salam A, Palimar P, Davis A. Statin sensitive lipid-retinopathy in familial hypercholesterolemia. J Clin Ophthalmol Res 2013;1:155-6

How to cite this URL:
Salam A, Palimar P, Davis A. Statin sensitive lipid-retinopathy in familial hypercholesterolemia. J Clin Ophthalmol Res [serial online] 2013 [cited 2021 Mar 7];1:155-6. Available from: https://www.jcor.in/text.asp?2013/1/3/155/116850

Although retinal exudates are a common accompaniment of diabetic macular edema, increased amounts of exudates have been independently linked with elevated serum lipid levels. ^[1] Lowering serum lipids likewise has been associated with decreased risk of lipid exudate formation and visual loss along with decreased risk of cardiovascular morbidity. ^[2]

We report a case of a 9-year-old boy with familial hypercholesterolemia (FH) and no history of diabetes noted to have extensive extravascular lipid deposits. These responded dramatically to the lowering of cholesterol levels with statins. Development of lipid exaudates in systemic conditions such as hyperlipidemia in the absence of diabetes is a poorly reported entity and to our knowledge, this is the first such report.

Case Report

A 9-year-old boy was referred by the optician with an incidental finding of scattered "hard exudates" in the right fundus, in October 2005. He was otherwise asymptomatic and these had been picked up at a routine school check up. Best corrected visual acuities were 6/5 in either eye. Dilated fundal examination showed scattered yellow deposits superior and inferior to the optic disc and along the inferior macula of the right eye [Figure 1]. The macula was otherwise dry and healthy. There were no micro/macrovascular changes adjacent to these "deposits." The left fundus was normal. There was no family history of any eye pathology. A diagnosis of Coats disease was not considered owing to the absence of vascular abnormalities. A routine review was arranged and he was seen on and off. Upon closer questioning, the mother was found to have a positive family history of hypercholesterolemia with premature coronary vascular disease and he was investigated biochemically in 2008. Serum lipid levels were as follows: Fasting cholesterol 6.5 mmol/l (normal: 3.1-5.0 mmol/l), low density lipoprotein (LDL) cholesterol 4.8 mmol/l (normal: 0.5-3.0 mmol/l), triglycerides 0.4 mmol/l (Normal: 0.2-2.0 mmol/l), and high density lipoprotein (HDL) cholesterol 1.5 mmol/l (normal: 1.0-2.0 mmol/l). There were no cutaneous xanthomas. All other biochemical tests including fasting glucose levels were normal. DNA testing showed deletion defect comprising exon 2-6 of the LDL receptor gene, same as his mother. In November 2008, his lipid profile was: Serum cholesterol 7.0 mmol/l. LDL cholesterol 5.6 mmol/l, HDL cholesterol 1.0 mmol/l, and triglycerides 1.0 mmol/l. Given the history of premature coronary vascular disease, he was started on Simvastatin 10 mg once daily. Nine months later, the cholesterol dropped to 5 mmol/l, LDL was 3.4 mmol/l, HDL cholesterol was 1.5 mmol/l, and triglycerides were 0.3 mmol/l. When reexamined routinely in the clinic in October 2009 (11 months posttherapy), the retinal exudates had resolved considerably [Figure 2]. There were no visible retinal vascular anomalies in either eye. Serial pictures remained unchanged until he stopped attending the clinic in 2011.

Figure 1: Fundus photograph of right eye at presentation showing lipid exudation without vascular changes

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Figure 2: Almost complete resolution of exudates of exudates after statins. Note healthy retinal vasculature

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Discussion

FH is an autosomal dominant metabolic disorder resulting in high levels of total cholesterol and LDL cholesterol. It is caused by mutations in the low-density lipoprotein receptor (LDLR) gene, located on chromosome 19. ^[3] The ocular manifestations in these conditions reported to date are arcus, xanthelasmas, tuberous xanthomas of the lids, lipemia retinalis, angiod streaks, and rarely "cholesterol deposits" in adults. ^[4] Lipid retinopathy results from lipoprotein leakage as hard exudates from retinal capillaries into the plexiform layer of the retina. There is extravasation and subsequent oxidation of LDL from endothelial cells due to break down of blood retinal barrier with subfoveal migration and subretinal fibrosis. ^[5],[6] Diabetes and hyperlipidemia are the most common denominators for hard exudates formation. ^[7],[8],[9] Elevated lipids contribute to vascular injury by a mechanism independent of hyperglycemia. ^[1] In particular, oxidized LDL promote cytokine production resulting in inflammation and fibrogenesis. One of the earliest case series by King et al. ^[10] compares the effect of restricted fat consumption in 40 diabetics with a striking 80% reduction of retinal exudates as opposed to 30% of treated group. Arsovska in their study on 38 diabetic patients over a 5-9 year follow up concluded that patients with elevated total and LDL were at a 2-fold higher risk of development of hard exudates than controls. ^[11] It has been shown recently that clinical benefits of statins on endothelial dysfunction result from production of isoprenoids, which are important lipid attachments for the posttranslational modification of a variety of proteins. Guanosine 5'-Triphosphate (GTP) and, are in part independent of their cholesterol lowering effects. They up-regulate the synthesis of nitric oxide, which is known to have a protective role in preventing vascular insult and thus microangiopathy. ^[12] Although, spontaneous resolution of hard exaudates is known to occur in 6-8 months, it would appear that lipid lowering therapy is more commonly associated with resolution of exudates in comparison to spontaneous resolution. ^[13] Our patient had an unchanged clinical picture for almost 3 years and a rapid resolution after initiation of therapy.

The unilateral exudative retinopathy solely due to an overload of systemic cholesterol levels is difficult to explain. In the absence of symptoms in the initial stage and presence of a definitive diagnosis in the later stages, neither the physicians nor the geneticists felt it necessary to carry out further investigations for carotid artery disease.

To the best of our knowledge such a unique occurrence in FH has not been reported in the literature before. We feel that this chance occurrence is an understated and under diagnosed entity and a prospective study (screening) in patients with FH would be invaluable. Furthermore, an expansion of the remit of lipid lowering therapy in treating exudative retinopathy would be an outstanding achievement, although their role is yet to be determined.

References

1.	Cusick M, Chew EY, Chan CC, Kruth HS, Murphy RP, Ferris FL 3rd. Histopathology and regression of retinal hard exudates in diabetic retinopathy after reduction of elevated serum lipid levels. Ophthalmology 2003;110:2126-33. [PUBMED]
2.	Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 1996;114:1079-84. [PUBMED]
3.	Hutton JK, Rourke RA. In: Molecular biology of the cardiovascular system. In: Stein JH, editor. Internal Medicine. Missouri: Mosby; 1998. p. 28-9.
4.	Blodi FC, Yarbrough JC. Ocular manifestations of familial hypercholesterolemia. Trans Am Ophthalmol Soc 1962;60:304-15. [PUBMED]
5.	Mingyuan W, Chen Y, Wilson K, Chirindel A, Ihnat MA, Yu Y, et al. Intraretinal leakage and oxidation of LDL in diabetic retinopathy. IOVS 2008;49:2679-85.
6.	Waller S, Thyagarajan, S, Kaplan, F, Viljoen A. Dramatic resolution of massive retinal hard exudates after correction of extreme dyslipidaemia. Eye (Lond) 2009;23:738.
7.	Gandhi JS. Lipids, diabetic maculopathy, and cardiovascular risk. Eye (Lond) 2004;18:108-9. [PUBMED]
8.	Ferris FL CK, Hoogwerf BJ. Serum lipids and diabetic retinopathy. Early Treatment Diabetic Retinopathy Study Research Group. Diabetes Care 1996;19:1291-3.
9.	Klein BE, Moss SE, Klein R, Surawicz TS. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, XIII: Relationship between serum cholesterol to retinopathy and hard exudate. Ophthalmology 1991;98:1261-5. [PUBMED]
10.	King RC, Dobree JH, Kok D, Foulds WS, Dangerfield WG. Exudative Diabetic Retinopathy spontaneous changes and effects of a corn oil diet. Br J Ophthalmol 1963;47:666-72. [PUBMED]
11.	Golubovic-Arsovska M. Association of dyslipidaemia with macular oedema and hard exaudates in diabetic maculopathy. Prilozi 2007;28:149-60. [PUBMED]
12.	Danesh FR, Kanwar YS. Modulatory effects of HMG-CoA reductase inhibitors in diabetic microangiopathy. FASEB J 2004;18:805-15. [PUBMED]
13.	Misra A, Vikram NK, Kumar A. Diabetic maculopathy and lipid-lowering therapy. Eye (Lond) 2004;18:107-8. [PUBMED]