We describe a 33-year-old woman who was seen for blurred vision of sudden onset in the right eye and was found to have a branch retinal arteriole occlusion associated with familial factor V Leiden polymorphism and rheumatoid factor positivity. Immunological screening results were positive only for rheumatoid factor, and screening for thrombophilia revealed factor V Leiden polymorphism. Family screening results for the factor V Leiden polymorphism were positive in the patient's mother, who had suffered thromboembolic episodes, and in 2 other siblings who are asymptomatic to date.
A 33-year-old white woman sought care because of a 2-week history of painless, blurred central vision and an inability to focus with her right eye. There was no history of pain, trauma, weight loss, fever, night sweats, arthralgias, rash, neurologic symptoms, or any eye problems. She had suffered from migraines since the age of 21 for which she was treated with atenolol, and she had stopped smoking 4 years previously.
The patient had had 2 normal pregnancies and 2 healthy children, aged 7 and 4 years. Family history revealed that her mother had had 2 episodes of cerebral hemorrhage and a pulmonary embolism as a result of taking contraceptive pills, and that a sister suffered from reflex nephropathy.
On examination she was found to be in good general health and normotensive. Visual acuity was 20/40 OD and 20/20 OS. On slitlamp examination, quiet anterior segments and normal intraocular pressures were seen. Ophthalmoscopic examination of the right eye revealed a 1.5–disc diameter cotton-wool spot in the macula (Figure 1, left). The fovea was spared. No other abnormality was seen and results of the left eye examination were normal. Humphrey visual field analysis showed a horizontal increase in the blind spot. Fluorescein angiography revealed slow filling and partial blockage of a retinal arteriole corresponding to the area of retinal pallor (Figure 2, left).
Left, Fundus photograph of the right eye showing a large cotton-wool spot in the superonasal part of the macula. Right, Fundus photograph of the same eye showing partial resolution of the cotton-wool spot at 4 weeks.
Left, Fluorescein angiogram in early arterial phase showing nonfilling of the affected retinal arteriole (arrow) close to the area of the retinal infarct. Right, Fluorescein angiogram showing delayed filling of the affected retinal arteriole (arrow) in the venous phase.
The patient was diagnosed as having a branch retinal arteriole occlusion and was started on a regimen of aspirin, 75 mg daily. Results from systemic evaluation revealed normal values for complete blood cells, glucose, serum electrolytes, creatinine, and liver function; a chest x-ray film showed no abnormalities. Immunological investigations revealed a positive rheumatoid factor at a titer of 1:320 on 3 occasions. Anticardiolipin antibodies for both IgG and IgM isotypes were tested and results were negative, and lupus anticoagulant was not detected. Findings from her coagulation screen disclosed a prolonged partial thromboplastin time. The protein C levels were normal, but activated protein C inhibition was reduced, a pattern compatible with genetic abnormality. Factor V Leiden polymorphism was detected by polymerase chain reaction. In view of her mother's thromboembolic history, the whole family was screened for the Leiden mutation, and findings were positive in the mother, a sister, and a brother. All the affected individuals, including our patient, were heterozygous for the mutation. A brain magnetic resonance imaging scan and echocardiogram showed no abnormalities, and no source of emboli or evidence of peripheral vascular disease was discovered.
The patient's visual acuity recovered to 20/20 OD over the next 6 months, and the cotton-wool spot resolved (Figure 1, right). She was reviewed by the internists who advised her to continue taking aspirin along with atenolol with the possibility of being started on treatment with warfarin sodium should she have another episode of thrombosis.
Retinal arteriole occlusions are rare in the younger population and usually result from valvular disorders, migraines, and hypercoagulability states, especially those induced by autoimmune conditions1 like antiphospholipid antibody syndrome and lupus.
The protein C anticoagulant system is physiologically important and inhibits coagulation by inactivating the procoagulant factors Va and VIIIa. A high prevalence of resistance to activated protein C has been seen in people with a history of venous thrombosis. This resistance appears to be inherited as an autosomal dominant trait.2 A single point mutation occurs in the factor V gene at nucleotide position 1691, which codes for a mutant factor V, where glutamine (Q) replaces arginine (R) at position 506, and this factor is now referred to as factor V:Q506, factor V:R506Q, or factor V Leiden.3 Owing to the variable penetrance of the mutation, clinical manifestations may vary and some carriers may remain asymptomatic. Heterozygotes have a 7-fold risk of thromboembolism whereas homozygotes have a 20-fold risk. The risk increases with age, and in heterozygotes, oral contraceptive use and pregnancy increase the risk to 15-fold. Factor V Leiden may also be associated with other defects such as protein C or S deficiencies, antithrombin III deficiency, and antiphospholipid antibodies.4
Retinal vein occlusion associated with resistance to activated protein C has been well documented.5,6 The factor V Leiden polymorphism is more usually associated with vein occlusions, and it is notable that our patient had arteriolar occlusion.
Factor V Leiden mutation associated with branch retinal arteriole occlusion was described recently in a 9-year-old girl who had concurrent thermolabile methylene tetrahydrofolate reductase7 mutation, which is also a weak thrombophilic factor. Our patient's test results were positive for rheumatoid factor, but she had no other autoantibody activity and no clinical history suggestive of the antiphospholipid syndrome. The rheumatoid factor could possibly point toward an underlying autoimmune state, which increases the propensity she has for occluded blood vessels. Another noteworthy factor was her history of migraine, which if severe can in rare cases be a causative factor for branch retinal arteriole occlusion.8 However, in her case the rheumatoid factor was not of a severe form, and she had not had a migrainous episode for more than a year. Her blurred vision was not preceded or accompanied by a headache or even an aura. Use of β-blockers is well known to potentiate vasoconstriction of retinal circulation, but our patient has safely used atenolol as a prophylactic treatment of migraine for the last 5 years.
Thus, retinal arteriole occlusion in young adults can occur as a result of multiple etiologic factors with factor V Leiden being a major contributor toward triggering a thromboembolic event. Vine and Samama3 have recommended that factor V:Q506 screening be done only for those patients who have a history of recurrent retinal vein occlusions or those with retinal vein occlusions and a personal or family history of thromboembolism. Our case illustrates that in young patients with retinal arteriole occlusions and a family history of thromboembolic disease, factor V screening could help in the diagnosis and management of the disease. Affected families and individuals should accordingly be advised to avoid other thrombogenic factors to prevent thromboembolic episodes.
Corresponding author: Sushma Dhar-Munshi, Department of Ophthalmology, Room 5.012, Lanesborough Wing, St George's Hospital, Blackshaw Road, London SW 17 0QT, England (e-mail: firstname.lastname@example.org).
Dhar-Munshi S, Ayliffe WH, Jayne D. Branch Retinal Arteriolar Occlusion Associated With Familial Factor V Leiden Polymorphism and Positive Rheumatoid Factor. Arch Ophthalmol. 1999;117(7):978-979. doi: