Introduction

Central retinal vein occlusion (CRVO) is a potentially blinding disease, whose pathophysiology remains unknown. We describe here a family with a high incidence of CRVO.

Case reports

Case 1

A 56-year-old woman (patient Ia) presented to one of us (SS) in February 1999 complaining of visual loss in the left eye. Her medical history comprised chronic headaches treated by oral propanolol. At initial examination, visual acuity (VA) was 20/20 OD, and 20/70 OS. Intraocular pressure (IOP) was 16 mmHg OD, 17 mmHg OS. Right fundus was normal. Left fundus showed perfused CRVO with macular oedema. A thorough medical and biological work-up (comprising dosage of protein C and S, antithrombin III, antiphospholipid antibodies, antinuclear antibodies, and plasma homocystein) did not reveal significant abnormalities. She was heterozygous for the C677T mutation of the methyltetrahydrofolate reductase (MTHFR) gene. One year later, CRVO occurred in the right eye. At that time, VA was 20/100 OD, and 20/50 OS. At the last visit in 2005, VA was 20/100 OD, 20/50 OS owing to bilateral macular oedema.

Case 2

Her brother (patient Id) developed CRVO in the right eye in July 1999 at age 72. He had a history of high blood pressure and myocardial infarction, and received antihypertensive therapy and coumadin. VA was counting fingers OD, 20/20 OS. Anterior segment examination of the right eye revealed rubeosis iridis, and an IOP of 23 mmHg. IOP was 16 mmHg OS. Right fundus examination revealed ischaemic CRVO. Left fundus was normal. Panretinal photocoagulation was subsequently performed in the right eye. Medical work-up (comprising dosage of erythrocyte sedimentation rate, fibrinogen, C, and S proteins, antiphospholipid antibodies, plasma homocystein, and of antithrombin III) was unremarkable. He was heterozygous for the C677T mutation of the MTHFR gene. In 2004, CRVO developed in the left eye. In 2005 he was seen by one of us (MP), and at that time VA was light perception OD, and 20/400 OS.

Case 3

The son of the propositus (patient IIa) developed CRVO in the left eye in 1998 at the age of 27. He had an unremarkable medical history. At initial examination by one of us (SS), VA was 20/20 OD, and 20/100 OS. IOPs were normal. Fundus examination was normal OD, and showed perfused CRVO OS. Levels of proteins C and S, of antithrombin III, of antinuclear antibodies, of antiphospholipidin and of homocystein were within normal limits. Blood pressure was normal. In 2003, CRVO developed in the right eye. Iterative intravitreal injections of triamcinolone acetonide were performed in the right eye to treat macular oedema. At the last examination in June 2005, VA was 20/30 OD, and 20/160 OS.

Among the asymptomatic patients, one of the sisters of the propositus, patient Ic, was examined by one of us (MP) at the age of 72. She was under treatment for high blood pressure and high IOP. VA was 20/20 in both eyes. In the left eye, there was an opticociliary shunt suggestive of an asymptomatic episode of CRVO. The other members (Ib, Ie, and IIb) had normal fundi. Neither the parents nor the grandparents of the affected subjects were consanguineous. The cause of the death of the parents of case 1 are cancer for the mother, and heart disease for the father. None had known ocular disease. The family pedigree is shown in Figure 1.

Figure 1
figure 1

Pedigree of the family. Filled circles and squares: bilateral CRVO; half-filled circles and squares: unilateral CRVO; + indicate patients that have been examined by us.

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Comment

In the literature, four reports of CRVO families, involving a total of 11 patients, have been published (Table 1). 1, 2, 3, 4

Table 1 Reported cases of familial RVO
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Such familial clustering of RVO is not per se a proof of the existence of a genetic predisposition to RVO. Indeed, given the little number of reported cases, these may be a coincidence. Moreover, most of these cases had significant risk factors for RVO such as arterial hypertension or glaucoma.5, 6, 7, 8, 9 However, an interesting finding is that offspring of affected patients had the disease at a younger age than their parents. Moreover, 46% had bilateral CRVO, and the mean age of onset was 45 years. Familial cases of CRVO cases appear thus to be more often bilateral (P<0.01) and to affect younger patients (P<0.05) than sporadic CRVO. 5, 6, 7 Therefore, the figure that emerges is that familial CRVO may be a specific pathological entity, and thus deserves further studies. If the hypothesis of a genetic cause for these cases is correct, the mode of transmission cannot be determined with so few cases, and the collection of additional data from them and from other families is required.