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Sir,

Interferon (INF) alpha is known to have antiviral, antifibroblastic and antitumour effects.1,2 It has been tried in the treatment of ocular disorders such as dendritic keratitis, subretinal neovascularisation in age-related macular degeneration,3 glaucoma filtering surgery, and ocular cicatricial pemphigoid.3,4 However, ocular side effects of INF-alpha are also being increasingly reported.3 We describe a case with severe proliferative retinopathy while on low-dose INF-alpha therapy.

Case report

A 69-year-old woman presented to the eye clinic with photophobia and reduced vision of gradual onset, via her optometrist. She was diagnosed to have chronic myeloid leukaemia 18 months ago. She had been treated with hydroxyurea with a good response and later (2 months from diagnosis) agreed to participate in a randomised clinical trial to assess the merits of low/high-dose INF treatment for chronic myeloid leukaemia. She was randomised to receive low INF, INF Alpha-N1 3 million IU, 5 days a week. She had not received any systemic steroid treatment. She was also hypertensive on atenolol. At the time of ophthalmic presentation, she was in haematological remission and had received 16 months of INF-alpha treatment. She had two transient ischaemic attacks (transient total loss of vision in the right eye lasting for 5 min) in the following few months, for which she received aspirin 150 mg daily.

Visual acuities on presentation were 6/12 in the right eye and 6/18 in the left eye. Anterior segment examination showed 1+ cells and flare in the anterior chamber of left eye, and bilateral early cortical lens opacities. Fundoscopy revealed bilateral optic disc neovascularisation, multiple cotton wool spots, venous dilatation and tortuosity, and peripheral retinal neovascularisation in the left eye (Figure 1). The different possibilities were retinal ischaemia secondary to leukaemia, ocular ischaemia, and INF-associated retinopathy. Leukaemia was considered less likely as the patient had normal blood counts on treatment before and during the course of INF therapy. Investigations performed for diabetes mellitus, carotid ischaemia, collagen vascular diseases, and sarcoidosis did not reveal any abnormalities. Carotid Doppler ultrasound showed bilateral atheromas but no significant stenosis. Fluorescein angiography documented the ischaemic retinopathy and retinal neovascularisation.

Figure 1
figure 1

Fundus fluorescein angiogram of the left eye: leakage from new vessels on the disc (NVD) and elsewhere (NVE).

Full size image

Argon laser panretinal photocoagulation was carried out in multiple sessions with fill-in laser undertaken on subsequent visits over the few months causing regression of proliferative retinopathy. INF treatment was stopped. The proliferative retinopathy gradually regressed; however, the left eye developed fibrous proliferation over the temporal arcades with macular tractional retinal detachment. Visual acuities by then had reduced to 6/24 in the right and 6/36 in the left eye. She subsequently underwent left vitrectomy and her visual acuity has stabilised to 6/24 in the left eye. She continues to be in haematological remission of leukaemia.

Comment

INF-alpha therapy has been known to cause a variety of ocular lesions.1,2 Typical lesions include cottonwool spots and retinal haemorrhages at the posterior fundus, particularly around the optic disc, secondary to retinal ischaemia, which usually appear within 3 months of the onset of therapy.3,5 The incidence of retinopathy is thought to depend on the initial dose of INF-alpha and patients receiving high dosages such as 9 × 106 IU/day, 6 days per week, are usually at increased risk of retinopathy. Diabetes and systemic hypertension are risk factors.1,6 The retinopathy may disappear spontaneously during therapy or rapidly after stopping therapy.3,5 Despite the retinopathy, subjective complaints are uncommon and visual acuity is not always impaired. Most patients with INF-associated retinopathy can continue with the planned course of INF therapy. Pathogenesis of INF-associated retinopathy is unknown, although some investigators have suggested deposition of immune complexes in the retinal vasculature and leucocyte infiltration that cause retinal ischaemia with resultant capillary nonperfusion and nerve fibre layer infarctions.3

Our patient was unusual because she developed severe, progressive proliferative retinopathy while on low-dose INF-alpha. Retinopathy needed extensive laser treatment and warranted stoppage of the drug. Retinopathy was first diagnosed on ophthalmic referral made 16 months after the induction of INF-alpha therapy. Mild anterior segment inflammation was an unusual feature. INF-induced retinopathy is not always self-limiting and benign. We recommend ophthalmic examination of patients pretreatment to look for pre-existing retinopathy and subsequent examinations while on treatment. If severe ocular toxicity occurs, INF therapy should be discontinued.1