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Effects of homozygous apolipoprotein A-1 deficiency on the cornea
  1. Y DOMNIZ,
  2. G L SUTTON,
  4. C M ROGERS,
  1. The Eye Institute, Sydney, Australia
  1. Dr Y Domniz, The Eye Institute, Level 3, 270 Victoria Avenue, Chatswood, 2067, Sydney, Australia ydomniz{at}

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Editor,—Apolipoprotein A-1 (Apo A-1) plays a central part in the metabolism of high density lipoproteins (HDL).1 Apo A-1 and apolipoprotein A-2 (Apo A-2) make up 80–90% of the protein content of HDL. The characteristics of this deficiency are low levels of HDL serum and Apo A-1, normal levels of triglycerides serum and high levels of LDL serum and total cholesterol.1-4 HDL concentration is inversely correlated with a risk of coronary heart disease (CHD).5 However, there is disagreement about the importance of normal Apo A-1 and HDL serum levels in preventing atherosclerosis.6 Signs of advanced atherosclerosis and early coronary heart disease were only found in some patients with Apo A-1 deficiency,3 5 and did not appear in other patients.4 6 Thus, in addition to low Apo A-1 levels, other cardiovascular risk factors must be present to cause premature atherosclerosis.5 7 Retinopathy, neuropathy, and corneal opacity are associated with this deficiency.5 8 9 Our report describes the corneal condition of a 37 year-old Sri Lankan woman with homozygous Apo A-1 deficiency.


A 37 year old Sri Lankan woman presented complaining of intermittent red eyes. The patient's vision was good and there were no abnormalities in her past general health. She reported having an unusual bluish appearance in her eyes since the age of 15 and reported that her two sisters had a similar corneal appearance, though neither of her brothers or parents were affected (Fig 1). Her parents' marriage was non-consanguineous. On examination her uncorrected visual acuity was 6/5 in both eyes. Both corneas had a dense arcus extending for 360° of the peripheral cornea. The bilateral corneal stromal opacity was slightly denser anteriorly than posteriorly (Fig 2). Corneal thickness was normal. The left eye was mildly injected. Intraocular pressure was normal (15–16 mm Hg) in both eyes throughout the follow up. Dilated fundus examination revealed a normal posterior pole. Specular microscopy, pachymetry, and photography were conducted. Specular microscopy revealed cell counts of 2776/2562 cells/mm right eye and 2826/2456 cells/mm left eye in two successive measurements. Episcleritis with no coincidental systemic disease was provisionally diagnosed. No abnormality was detected on examination of the chest, heart, lungs, neck, and tonsils.

Figure 1

Right eye. Corneal appearance on presentation.

Figure 2

Left eye. Slit lamp appearance: showing increased corneal deposits.

Blood pressure was 120/70. Fasting blood samples were taken for lipids, plasma protein, thyroid function, immunoglobulins, VDRL, FBC, ESR, and IEPG. The patient was treated in both eyes with topical prednisolone sodium phosphate 0.5% four times daily and dexamethasone phosphate 0.1% twice daily. After 1 week the episcleritis disappeared. Blood results showed increased total cholesterol (7.79 mmol/l, normal 3.0–5.5), LDL (5.05 mmol/l, normal 1.7–3.5), and total protein (81 g/l, normal 59–78). Normal triglycerides (1.8 mmol/l, normal 0.2–2.0) and apolipoprotein B (1.51 g/l, normal 0.70–1.60) levels were recorded, with decreased HDL cholesterol (0.14 mmol/l, normal 0.83–1.87) and apolipoprotein A-1 (0.15 g/l, normal 1.10–2.00). Serum albumin (45 g/l, normal 37–46) and bilirubin (7 μmol/l, normal 3–18) were within normal range. Immunological serum specimens were negative for all of the above mentioned factors including ANA. Blood TSH level was normal (0.7 μm/l, normal 0.1–3.8). Protein electrophoresis showed increased total protein (87 g/l, normal 63–80), increased α2 globulin (11 g/l, normal 2–9) with a low α1 (1.8 g/l, normal 2–4). Blood count was WBC 9.43 ×109 g/l (3–10), Hb 12.3 g/dl (11.5–16.5), PLT 375 × 109 g/l (150–400) with neutrophil 6.6 × 109g/l (2.0–7.5), lymphocytes 3.3 × 109 g/l (0.8–4.0), monocytes 0.6 × 109 g/l (0.0–1.0), and eosinophils 0.5 × 109 g/l (0.0–0.5). ESR was high (38 mm in the first hour, normal 0–30). A diagnosis of severe homozygous lipoprotein A-1 deficiency syndrome was confirmed. There was no corneal change throughout the 18 months of follow up.


The differential diagnosis of our patient's bilateral corneal stromal opacity with advanced arcus senilis included Tangier disease, fish eye disease, Schnyder central crystalline dystrophy, and apolipoprotein A-1 deficiency. Schnyder central crystalline dystrophy is characterised by elevated serum cholesterol. A disc-shaped pattern of cholesterol crystals deposits are located in the centre of the cornea at the level of Bowman's layer and the anterior part of the stroma. Our patient had bilateral diffuse stromal involvement. Tangier disease is characterised by low levels of HDL, apolipoprotein A-1 and LDL, mild hypertriglyceridaemia and cholesterol ester deposition in the tonsils (orange tonsils), liver (hepatomegaly), spleen (splenomegaly), lymph nodes (lymphadenopathy), Schwann cells (peripheral neuropathy), and bone marrow.10 The low levels of only HDL and apolipoprotein A-1 in our case enabled us to reject the diagnosis of Tangier disease. Fish eye disease is characterised by low serum levels of HDL and total cholesterol, mild hypertriglyceridaemia, and deficiency of both apolipoprotein A-1 and apolipoprotein A-2.11 Although our patient's blood level of HDL and apolipoprotein A-1 were both low, the blood level of cholesterol was high and the triglycerides and apolipoprotein A-2 were normal. These findings are uncharacteristic of fish eye disease. Apolipoprotein A-1 deficiency is an autosomal recessive disease. The corneal clouding is due to cholesterol deposition and is affected by the severity of the apolipoprotein A-1 deficiency. The corneal lipid deposits are less dense at the centre and resemble small hazy white dots. In the periphery the denser deposition resembles arcus senilis. Apo A-1 deficiency was confirmed by serum analysis measures, which in our patient was 0.15 g/l (normal 1.1–2.0). Genetic analysis showed that the patient has the homozygous form of apolipoprotein A-1 deficiency. Her high LDL level (6.0 mmol/l normal 1.7–3.5) will need to be lowered with medication in order to prevent future atherosclerosis and coronary heart disease. Although there is no effective treatment for the cornea, an accurate diagnosis is essential in order to treat high LDL and total cholesterol levels and reduce the risk of renal failure and coronary heart disease.