LUPUS: A GP Guide to Diagnosis
Ocular manifestations of systemic lupus erythematosus are unusual. Broadly, they can be divided into those affecting either the front or the back of the eye. Ocular toxicity has been reported as a result of hydroxychloroquine therapy.
Approximately 25% of lupus patients will have evidence of keratoconjunctivitis sicca (dry eyes). The main symptoms are of gritty, irritable, uncomfortable eyes that may be associated with some redness. Vision is unaffected, there is no pain, photophobia or discharge.
Artificial tear substitutes, instilled as drops or a gel, usually give relief of symptoms but may need to be used on a frequent basis.
This is an unusual but potentially sight-threatening condition and may be an important indication of the severity of the lupus. One or both eyes may be involved and patients complain of pain, often so severe that it wakes them at night. There is an area or areas of intense redness with normal visual acuity, no photophobia or discharge.
REFER URGENTLY TO AN OPHTHALMOLOGIST
Mild cases usually require the use of oral non-steroidals. Failure of treatment or severe cases will need systemic immunosuppression in the form of oral corticosteroids and in resistant cases pulsed intravenous methylprednisolone and cyclophosphamide.
Conjunctivitis and episcleritis have been described but are rare.
Conjunctivitis can be treated with a course of antibiotic drops. Episcleritis, which may present with patches of redness, normal vision, no pain or photophobia but occasional discomfort and no discharge, may be a self-limiting condition. Oral non-steroidals such as flurbiprofen can be effective but should only be prescribed if there are no contra-indications as a result of lupus. Topical corticosteroids have a role in resistant cases but should normally only be prescribed under ophthalmic supervision.
Retinal findings in lupus may result from several pathophysiological mechanisms, including small vessel vasculitis, large vessel occlusive disease, secondary systemic hypertension and anaemia. Ocular complications tend to occur in acutely ill patients with active systemic disease.
Classic findings are cotton wool spots and retinal haemorrhages which may be found in 5-15% of patients. This microangiopathy probably results from the vasculitis associated with immune complex deposition in the small vessels. A prospective clinical study revealed that 88% of patients with lupus retinopathy had active systemic disease. Furthermore, lupus patients with retinopathy had a significantly decreased survival compared with lupus patients without retinopathy. Visual loss is uncommon and the patients may be asymptomatic.
The retinopathy improves with treatment of the systemic disease.
Far fewer patients with lupus retinopathy develop a severe retinal vasculitis with possible progression to proliferative retinopathy. The visual prognosis is much worse with more than 50% of affected eyes seeing 6/60 or worse. The underlying process is characterised by diffuse arteriolar occlusion with extensive capillary non-perfusion and retinal neovascularisation may result. This may present as a gradual loss of vision or sudden loss resulting from a vitreous haemorrhage secondary to the retinal neovascularisation. Tractional retinal detachment may occur. Severe retinopathy is typically associated with active systemic disease and with CNS lupus in particular.
Immunosuppression, primarily with corticosteroids, is the mainstay of therapy. Laser photocoagulation for proliferative retinopathy (similar to its use in diabetic retinopathy) is felt to be beneficial. Rarely, surgical intervention is required if the vitreous haemorrhage fails to clear or for retinal detachment.
Branch and central retinal vein or arterial occlusions can occur. Arterial occlusions will result in a more profound, usually permanent visual loss. Arteriolar, particularly branch, occlusions may form part of the antiphospholipid antibody syndrome. Although venous occlusions often result in permanent loss, some may recover vision with time. Retinal ischaemia may be a complication and retinal neovascularisation may result, particularly after central retinal vein occlusion. Symptoms are of sudden, painless loss of vision.
To monitor for any further complications, such as retinal ischaemia and treat as appropriate. To ensure adequate control of the systemic disease.
Typical retinal vascular changes can be seen in those patients who are hypertensive but these changes can be mistaken for lupus retinopathy and vice versa. Patients may be asymptomatic but would complain of sudden central visual loss if they developed a complication, such as a branch retinal vein occlusion.
The changes often resolve with reduction of the blood pressure.
In some cases, peripheral, blotchy intraretinal haemorrhages may reflect the anaemia associated with thrombocytopaenia more than the vasculitic component of the disease.
The changes often resolve with resolution of the anaemia.
Occasionally, the choroid (the layer beneath the retina) can be involved. Lupus choroidopathy results in multifocal serous detachments of the retina and underlying retinal pigment epithelium. These types of non-rhegmatogenous detachments (i.e. with no retinal hole) may be difficult to see with a direct ophthalmoscope. Visual loss is variable depending on the extent of macular involvement.
The detachments may regress with improved control of the systemic disease.
Neurological complications of lupus are seen in 25-75% of patients. Several neuro-ophthalmological manifestations of lupus have been reported, including ischaemic optic neuropathy and retrobulbar neuritis. Ischaemic optic neuropathy presents with sudden visual loss, often associated with an inferior altitudinal field loss. This type of field loss affecting the horizontal meridian easily distinguishes it from more posterior visual pathway field defects which obey the vertical meridian. The optic disc is pale and swollen. A swollen optic disc in lupus may also be secondary to hypertension, central retinal vein occlusion and increased intracranial pressure from intracranial disease. Retrobulbar neuritis results in a central or paracentral scotoma, red desaturation, pain on ocular movement and a relative afferent pupillary defect. The optic disc appears normal and the condition may be difficult to differentiate from that seen in association with demyelination. There is an association between neuro-ophthalmological disease and the antiphospholipid antibody syndrome. Retrochiasmal visual problems, such as transient amaurosis, visual hallucinations and homonymous field defects have all been described.
Systemic corticosteroids are the treatment of choice but although a return of vision would be expected with retrobulbar neuritis it may not occur after ischaemic optic neuropathy.
ALL BACK OF THE EYE PROBLEMS SHOULD BE REFERRED TO AN OPHTHALMOLOGIST
Hydroxychloroquine is frequently prescribed by rheumatologists for lupus and by dermatologists for cutaneous lupus. It binds to melanin and interacts with nucleic acids. Although irreversible retinopathy has been described, this has occurred at total doses in excess of those currently recommended. The literature and contemporary practice favour the use of low-dose hydroxychloroquine which confers minimal risk. In six case series with a total of some 1500 patients treated with hydroxychloroquine only one case of retinopathy with visual loss was observed. In the largest single series one patient out of 1027 developed retinopathy after seven years. Where doses of hydroxychloroquine were kept below 6.5mg/kg/day lean body weight, no cases of toxicity were found in 973 patients followed. Nevertheless, two cases of retinopathy have been reported when the drug was used for > 6 years.
Hydroxychloroquine toxicity, although rare, can result in an impairment of visual acuity and central visual field disturbance. Clinically, this is seen as a granular appearance to the macula or the characteristic "Bull's eye" maculopathy. At this stage the maculopathy is irreversible. Much debate exists with regards to screening for hydroxyquinolone toxicity as ocular damage is highly unusual, but when macular changes do occur they are irreversible. The 1998 Royal College of Ophthalmologists Guidelines for Screening describes recommendations for good practice in rheumatology and dermatology clinics. It recommends a baseline assessment by the physician (and not ophthalmologist) and thereafter annual evaluations. Referral to an ophthalmologist is appropriate if the patient has visual impairment or eye disease at baseline assessment or if the patient develops a change in visual acuity or blurred vision whilst on treatment.
Prof. Philip I. Murray
Academic Unit of Ophthalmology
Birmingham and Midland Eye Centre
City Hospital NHS Trust
Dudley Road
Birmingham, B18 7QU