|Year : 2022 | Volume
| Issue : 2 | Page : 369-370
Corneal arcus and low serum high-density lipoproteins: A report of two cases of probable Fish eye disease
Pallak Kusumgar1, Cynthia Amrutha Sukumar2, Shipra Rai2, Yogish Subraya Kamath3
1 Cornea and Refractive Surgeon, Arihant Hospital, Nagpur, Maharashtra, India
2 Department of Medicine, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Ophthalmology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
|Date of Submission||04-Jul-2021|
|Date of Acceptance||27-Sep-2021|
|Date of Web Publication||13-Apr-2022|
Yogish Subraya Kamath
Department of Ophthalmology, Kasturba Medical College-Manipal, Manipal Academy of Higher Education, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
We report two cases with dense corneal arcus with abnormally low levels of serum high-density lipoproteins. One case with arcus senilis had a history of corneal clouding since youth but no systemic associations. The other case had an arcus juvenilis with anemia and hepatosplenomegaly but an absence of renal involvement. The genetic analysis of this case was performed and was suggestive of lecithin-cholesterol aminotransferase deficiency.
Keywords: Arcus senilis, corneal diseases, cholesterol, HDL, lecithin cholesterol acyltransferase deficiency, lipoproteins
|How to cite this article:|
Kusumgar P, Sukumar CA, Rai S, Kamath YS. Corneal arcus and low serum high-density lipoproteins: A report of two cases of probable Fish eye disease. Indian J Ophthalmol Case Rep 2022;2:369-70
|How to cite this URL:|
Kusumgar P, Sukumar CA, Rai S, Kamath YS. Corneal arcus and low serum high-density lipoproteins: A report of two cases of probable Fish eye disease. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2023 Jun 2];2:369-70. Available from: https://www.ijoreports.in/text.asp?2022/2/2/369/342902
The deposition of lipids in the peripheral corneal stroma in the form of a ring concentric to the limbus is called the corneal arcus, which may be seen as a physiological age-related change (arcus senilis) or may be associated with dyslipidemias when seen in the young (arcus juvenilis)., We report two cases with dense arcus and corneal haze with low levels of serum high-density lipoproteins (HDL). Clinically, a diagnosis of partial lecithin cholesterol aminotransferase enzyme (LCAT) deficiency was made. This rare autosomal recessive condition, also called “Fish-eye disease” (FED) due to the ocular resemblance to eyes of boiled fish, has a prevalence of 1:1,000,000. In complete LCAT deficiency, in addition to corneal opacification, anemia, hepatosplenomegaly, and renal impairment are seen. Although direct confirmation based on the identification of the enzyme levels of this rare condition was not possible, genetic analysis done in one case revealed complete LCAT deficiency.
| Case Series|| |
A 64-year-old male presented with diminution of vision in both eyes since childhood. His best-corrected visual acuity was (OD) 6/24, N14; (OS) 6/18, N14. The cornea had a dense arcus senilis with multiple small dot-like gray-white opacities forming mosaic patterns in the stroma in both eyes [Figure 1]a,[Figure 1]b,[Figure 1]c. The rest of the ocular examination, including the intraocular pressure and fundus, were within normal limits. Pachymetry showed increased corneal thickness in both eyes [(OD) 580 μm; (OS) 610 μm]. Although he gave a family history suggestive of similar symptoms in other members, they could not be evaluated due to logistic reasons. The tonsils and cardiovascular evaluation revealed no abnormalities. He was not on any systemic or topical medications.
|Figure 1: (a and b) Diffuse illumination photographs of the eyes of Case 1 depicting dense arcus and corneal haze; (c) slit image showing stromal haze; (d) appearance of eye after penetrating keratoplasty; (e and f) diffuse illumination photographs of the eyes of Case 2 depicting arcus juvenilis]|
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Plasma lipid profile revealed markedly low HDL level [6.0 mg/dL (Normal: 40–60 mg/dL)] and highly raised total cholesterol: HDL ratio [19 (Normal: <5)].
He underwent penetrating keratoplasty 6 months later for corneal clouding at another center. [Figure 1]d. Unfortunately, a histopathological examination of the removed cornea was not available.
A 26-year-old lady with generalized weakness and pedal edema since 6 months was referred from the Internal Medicine department for an ophthalmological evaluation. Her best-corrected vision was 6/6, N6 in both eyes, with corneal examination revealing a white stromal deposit concentric to the limbus, resembling a prominent arcus juvenilis [Figure 1]e, [Figure 1]f Rest of the anterior and posterior segments were within normal limits. Systemically she had hepatosplenomegaly with anemia.
Plasma lipid profile showed hyper trygliceridemia [307 mg/dL (Normal: 60–150 mg/dL)] and low HDL levels (18 mg/dL) with a total cholesterol: HDL ratio being 6.6. Sanger sequencing of the LCAT gene (NM_000229.1) showed the presence of the known pathogenic variant c. 1034C > T in exon 6, suggestive of Norum disease. However, her blood urea and serum creatinine were within normal limits and she did not have proteinuria.
She was conservatively managed and advised an annual ophthalmological review.
| Discussion|| |
The corneal arcus is a common feature seen in the general population and has been associated with dyslipidemia and increased cardiovascular risk. The presence of low levels of HDL in the lipid profile is usually due to intake of certain drugs, including beta-blockers, androgens, and thiazide diuretics, and systemic diseases, including chronic renal failure, dysthyroidism, and hepatitis. Very low levels of HDL may be seen in rare inherited diseases, including familial LCAT deficiency. FED is an inherited syndrome with corneal clouding and was first reported in a Swedish family with marked reduction of HDL and elevated low-density lipoproteins, in addition to the corneal opacity. A mutation in the LCAT gene located on chromosome 16 (16q22.1) results in the occurrence of this autosomal recessive condition. The codon 123 mutation is responsible for the milder phenotype with partial LCAT deficiency in fish-eye disease and codon 4 mutation results in the more severe phenotype of complete LCAT deficiency in Norum disease.
In Case 1, bilateral progressive corneal opacities and arcus senilis were seen in the eyes but without signs of atherosclerosis, hepatomegaly, splenomegaly, or lymphadenopathy. The history of early-onset and other family members being affected was suggestive of an inherited disorder. The very low levels of HDL, with normal total cholesterol levels, were also in favor of a clinical diagnosis of FED. Although Schnyder corneal dystrophy was a close differential, the markedly low HDL level was in favor of FED. However, the lack of LCAT enzyme levels and genetic analysis due to poor accessibility to diagnostics and financial constraints was a major drawback in confirmation of the diagnosis.
In Case 2, a prominent arcus juvenilis with stromal cloudiness, associated with systemic features of hepatosplenomegaly, anemia, low HDL levels, and hypertriglyceridemia, was suggestive of complete LCAT deficiency. The genetic analysis also confirmed the same. However, the absence of renal involvement was unusual.
The management of this condition involves the systemic control of hyperlipidemia and monitoring for cardiovascular diseases. Penetrating keratoplasty may be performed for visual rehabilitation in cases with advanced corneal opacification.
| Conclusion|| |
In both cases, our inability to gain access to one or all diagnostic facilities, as well as the lack of screening of family members, points to the need for increased awareness of this rare but potentially transmissible and morbid condition. The need to investigate the lipid profile in unusually dense arcus senilis and all arcus juvenilis patients is also highlighted.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Segal P, Insull W Jr, Chambless LE, Stinnett S, LaRosa JC, Weissfeld L, et al
. The association of dyslipoproteinemia with corneal arcus and xanthelasma. The Lipid Research Clinics Program Prevalence Study. Circulation 1986;73:I108-18.
Carlson LA, Philipson B. Fish eye disease. A new familial condition with massive corneal opacities and dyslipoproteinaemia. Lancet 1979;2:922-4.
Ang M, Wong W, Park J, Wu R, Lavanya R, Zheng Y, et al
. Corneal arcus is a sign of cardiovascular disease, even in low-risk persons. Am J Ophthalmol 2011;152:864-71.e1.
Lucchi T, Calabresi L, Pinto A, Benetti E, Arosio B, Simonelli S, et al
. A woman with low HDL cholesterol and corneal opacity. Intern Emerg Med 2012;7:533-7.
Funke H, von Eckardstein A, Pritchard PH, Albers JJ, Kastelein JJ, Droste C, et al
. A molecular defect causing fish eye disease: An amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity. Proc Natl Acad Sci U S A 1991;88:4855-9.
Weiss JS, Khemichian AJ. Differential diagnosis of Schnyder corneal dystrophy. Dev Ophthalmol 2011;48:67-96.
Zemsky CJ, Sherman SW, Schubert HD, Suh LH. Case report: Management of corneal clouding from Lecithin: Cholesterol acyltransferase deficiency. Optom Vis Sci 2019;96:137-41.