Severe vaso-occlusive retinopathy associated with systemic lupus erythematosus

Introduction. Systemic lupus erythematosus (SLE) is a systemic idiopathic autoimmune inflammatory disease, with multiple organ involvement. Severe vaso-occlusive retinopathy is a rare, sight threatening lupus-related manifestation of the disease, which is more common in patients with coexisting antiphospholipid syndrome. Case report. We reported a 36-year-old female with severe vaso-occlusive retinopathy that manifested in the absence of antiphospholipid syndrome. In a 4-year follow-up, despite aggressive systemic corticosteroid and immunosuppressive therapy and panretinal laserphotocoagulation treatment, the disease progressed to retinal neovascularisation, neovascular vitreoretinopathy, neovascular glaucoma and, consecutively, severe visual loss. As the final option for preservation of visual function, pars plana vitrectomy with laserphotocoagulation was performed and had good results. Progression of ophthalmological findings indicated the progression of the systemic disease, as well as neurolupus. Conclusion. Severe vaso-occlusive retinopathy occurred as the ophthalmological manifestation of SLE in the absence of antiphospholipid syndrome, but correlated with neurolupus and led to visual deterioration despite the treatment.


Introduction
Systemic lupus erythematosus (SLE) is an idiopathic autoimmune inflammatory disease that can affect multiple organs.The main features of the disease include the presence of circulating autoantibodies to one or more components of cell nuclei, generation of circulating immune complexes and acti-vation of complement system resulting in tissue destruction 1 .Severe vaso-occlusive retinopathy is a rare lupus-related manifestation with poor visual prognosis, more common in patients with coexisting antiphospholipid syndrome [1][2][3] .
We reported a 36-year-old female with SLE and severe vaso-occlusive retinopathy that occurred in the absence of antiphospholipid syndrome.

Case report
In April 2008, a 36-year old female was admitted to the Clinic due to a sudden loss of vision in her right eye.Visual acuity in the right eye was 0.5/60 and in the left 0.3.The patient had been diagnosed with SLE 6 years before according to the international criteria proposed by the American College of Rheumatology 4 , and was treated with corticosteroids and antimalarial agents (chloroquine 250 mg per day).Ophthalmological examination revealed perivascular sheathing, extensive cotton-wool spots, intraretinal haemorrhages, retinal oedema and wide areas of vascular occlusion on the periphery of both eyes (Figure 1).Fluorescein angiography revealed bilateral complete obliteration of macular capillaries and widespread occlusion of small retinal vessels (Figure 2).According to the advice of the rheumatologist, three-daycourse pulse dose of methylprednisolone (1000 mg iv), followed by oral prednisolone 80 mg per day were introduced, as well as intravenous cyclophosphamide 500 mg administered in two-week regimen during the first two months and then continued once a month.After the treatment, visual acuity improved to 2/60 in the right eye and 0.5 in the left.
Further investigations were performed at the Institute of Rheumatology.Laboratory analyses showed elevated erythrocyte sedimentation rate, leucopenia, thrombocytopenia and normal erythrocyte count, haemoglobin rate and biochemical analyses.In immunoserology, elevated titres of antinuclear antibodies and circulating immune complexes were present, while other analyses (anticardiolipin antibodies and lupus anticoagulant) were negative.Renal function was normal.Objectively, the patient had iatrogenic Cushing syndrome with corticosteroidinduced obesity, hirsutism, osteoporosis and hypertension.On chest radiography, small pleural adhesion was detected in the right side.Due to the risk of development of neurolupus, magnetic resonance imaging (MRI) of endocranium was performed and punctiform ischemic lesions were detected in the corona radiata.
One year later, large areas of retinal ischemia persisted in both eyes with high risk of retinal neovascularization.Laser photocoagulation was performed in order to impede formation of new vessels.However, despite the aggressive treatment, one year later disc neovascularization with preretinal haemorrhage in the right eye and neovascularization elsewhere (temporal and nasal periphery) in the left eye developed.Panretinal photocoagulation continued (Figure 3) and after the treatment, visual acuity was 1/60 in the right eye and 0.3 in the left one and intraocular pressure was within normal limits with no neovascularisation in iridocorneal angle.Progression of the eye disease was noted three years later, with sudden visual loss in the single functional left eye.Visual acuity deteriorated to light perception bilaterally, due to dense vitreous haemorrhages.Also, neovascularisation in iridocorneal angle was noted in the right eye with intraocular pressure in 40 + mmHg range, which could not be controlled even with maximum medicamentous treatment.Vitreoretinal surgery (pars plana vitrectomy, endolaser and phaco) was performed in the left eye, because it was estimated that it has more visual potential.After the surgery visual function improved to 0.1 and was stabile for 18 months.During the follow up, repeated analyses for antiphospholipid antibodies were negative.

Discussion
SLE is an autoimmune inflammatory disease characterized by the numerous autoimmune phenomena and lesions in multiple organ systems 5 .Although eye findings are not listed as the criteria for SLE diagnosis, the thrombotic and inflammatory processes associated with SLE, can affect any part of the eye and result in manifestations such as keratoconjunctivitis sicca, scleritis, uveitis and retinal involvement 6 .Retinopathy in SLE is the second most common (after keratoconjunctivitis sicca) ophthalmological manifestation and usually is presented with cotton-wool spots, with or without intraretinal haemorrhages 2, 5, 6 .Depending on the study group, SLE retinopathy was reported to be present in 3.3-28.1% of all SLE patients, with the incidence rising at the advanced stages of the systemic disease 7,8 .A severe variant of retinal vaso-occlusive disease is less common and may include central or branch retinal vascular occlusion or diffuse vasoocclusive retinal disease [9][10][11] and the latter occurred in the presented case.Visual impairment is usually secondary to ischemic retinopathy and higher incidences were reported in association with antiphospholipid syndrome (APC) 1, 5 .However in the presented case, there were no evidences of this state.
Similar to the presented case, Mendrinos et al. 9 reported a case of bilateral combined central retinal artery and ve-in occlusion associated with normal levels of antiphospholipid antibodies and magnetic resonance imaging (MRI) confirmed central nervous system (CNS) vasculitis.The patient was treated with intravenous, followed by oral prednisone and cyclophosphamide, but unfortunately, despite all interventions, extensive vaso-obliteration led to permanent vision impairment.Also, Ho et al. 11 reported a case of bilateral severe SLE vaso-occlusive retinopathy in the absence of antihpospholipid syndrome that led to devastating vision deterioration.In addition, Zou et al. 10 reported a case of bilateral central retinal artery occlusion (CRAO) as the primary manifestation of with normal levels of antiphospholipid antibodies.Visual acuity deteriorated despite the systemic corticosteroid and immunosuppressive treatment 11 .
Severe diffuse bilateral vaso-occlusive retinopathy as a complication of SLE, with the normal concentration of antiphospholipid antibodies is a rare complication in SLE.This type of retinopathy may be explained by the immune complex deposition, microthrombosis and endothelial damage in small blood vessels in the retina and choroid 2 .In the presented case, permanent loss of vision developed despite the treatment (systemic corticosteroid, immunosuppressive therapy and panretinal laserphotocoagulation).The patient's poor visual acuity along with bilateral optic nerve pallor could be attributed to posterior ischaemic optic neuropathy.Vitreoretinal surgery was the final option that impeded the retinal proliferative disease and improved the visual function.Furthermore, patient had vaso-occlusive retinopathy associated with similar changes in CNS and therefore had to receive the most aggressive systemic treatment, since it was shown that patients with neurolupus have the poorest prognosis in respect to survival rates 6 .

Conclusion
Vaso-occlusive retinopathy is a rare lupus-associated complication and its presence is highly suggestive for SLE activity.It is usually, although not exclusively, a manifestation of antiphospholipid syndrome.Treatment should be prompt with close communication with rheumatologists and aimed to prevent further thrombosis and complications arising from neovascularisation.

Fig. 1
Fig. 1-a) Fundus colour photograph of the right eye showing vaso-occlusive retinopathy with cotton-wool spots and retinal oedema (April 2008), and b) Fundus colour photograph of the left eye showing vaso-occlusive retinopathy with intraretinal haemorrhages, cotton-wool spots and retinal oedema (April 2008).

Fig. 3
Fig. 3 -a) Fundus colour photograph of the right eye showing neovascularization at disc, intravitreal haemorrhage and scars after panretinal laserphotocoagulation (February 2010), and b) Fundus colour photograph of the left eye showing neovascularization elsewhere, preretinal haemorrhage and scars after laserphotocoagulation nasally and below the optic disc (February 2010).