Lupus retinopathy manifesting unilateral neovascular alterations: A case with 15 years of follow-up

Abstract

Purpose

To report a rare case of lupus retinopathy, characterized by unilateral neovascular alterations and asymmetrical clinical progression.

Observations

A 32-year-old woman diagnosed with systemic lupus erythematosus (SLE) was referred to the ophthalmology department with decreased and blurred vision in the right eye. The patient was diagnosed with SLE at 31 years of age owing to cutaneous lupus, oral ulcers, and arthritis with a positive antinuclear antibody. Initial fundus assessment showed bilateral cotton wool spots predominantly in the right retina, and fluorescein angiography revealed nonperfusion areas exclusively in the right retina. Therefore, bilateral lupus retinopathy was diagnosed. Laboratory tests indicated the absence of concurrent antiphospholipid syndrome. The patient discontinued follow-up visits to the ophthalmology department for 1 year. Upon re-examination, a prominent neovascular membrane and vitreous hemorrhage were observed in the right eye, whereas cotton wool spots in the left eye resolved. The patient underwent lens-sparing pars plana vitrectomies two times. In the 15-year period after the vitrectomies, no recurrence of neovascular alterations in the right eye was noted.

Conclusions and importance

Although lupus retinopathy generally presents with similar severity in both eyes, the patient in this study demonstrated unilateral neovascular alterations and asymmetrical clinical progression. These findings indicate the requirement for careful monitoring of patients with asymmetrical lupus retinopathy, even in those without antiphospholipid syndrome.

Highlights

• •Lupus retinopathy progresses to a severe neovascular state.
• •Asymmetrical severity and clinical progression can occur.
• •Vaso-occlusive alterations develop even without antiphospholipid syndrome.

1. Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease with different clinical presentations that affects several organs.^1,2 Lupus retinopathy, a complication characterized by retinal vascular occlusion, occurs in 3 %–29 % of patients with SLE. This retinopathy is considered to develop from immune complex deposition and antibody-related vasculitis and thrombosis.^3,4 Common manifestations are cotton wool spots, microaneurysms, hard exudates, and retinal hemorrhages. Retinal neovascularization secondary to vaso-occlusive retinopathy is rare, with few cases previously reported.^3,5,6 Moreover, the disparity in severity between both eyes has not been well investigated, although retinopathy usually presents bilaterally. We describe a unique case of lupus retinopathy with severe unilateral neovascular alterations that was followed up for over 15 years.

2. Case report

A 32-year-old woman was referred to the ophthalmology department with decreased and blurred vision in her right eye, which developed while she was undergoing oral steroid treatment (30 mg/day prednisolone) for SLE, prescribed by the internal medicine department. One month before the referral, she underwent three cycles of intravenous methylprednisolone therapy (500 mg/day for three consecutive days per cycle) as a general treatment for SLE. The initial fundus assessment showed bilateral cotton wool spots, which were more pronounced in the right retina (Fig. 1-A, B), with visual acuities of 20/25 and 20/20 in the right and left eyes, respectively. Subsequent fluorescein angiography revealed marked non-perfusion areas in the right retina, with no apparent non-perfusion area in the left retina (Fig. 1-C, D). Furthermore, optical coherence tomography revealed macular edema in the right eye (Fig. 1-E). Therefore, the patient was diagnosed with bilateral lupus retinopathy. Laboratory tests for antiphospholipid antibodies and beta-2 glycoprotein were negative, indicating the absence of concurrent antiphospholipid syndrome (APS).

Fig. 1.

Initial fundus photograph showing widespread cotton wool spots in the right fundus (A), with only a few cotton wool spots in the left fundus (arrowheads) (B). The initial fluorescein angiography illustrating a prominent non-perfusion area in the right fundus (arrows) (C) but no apparent ischemic changes in the left fundus (D). The initial optical coherence tomography visualizing macular edema exclusively in the right fundus (asterisk) (E, F).

Initial ophthalmological treatment involved a sub-Tenon steroid injection of triamcinolone acetonide (20 mg) administered to the right eye of the patient. Subsequently, the patient discontinued follow-up visits to the ophthalmology department because of a lack of improvement in vision.

One year after the injection, the patient returned to our department with further deterioration of vision in the right eye. The patient was maintained on oral steroid therapy and the dosage was reduced to 10 mg/day prednisolone at the time of the patient's return. The patient's right visual acuity declined to 20/400, whereas the left visual acuity remained at 20/20. Fundus examination and fluorescein angiography revealed a severe neovascular membrane and vitreous hemorrhage in the right eye (Fig. 2-A, C), whereas the left eye revealed resolution of the cotton wool spots (Fig. 2-B). Magnetic resonance angiography and neck ultrasonography did not reveal stenosis, occlusion, or plaque in either internal carotid artery. The right eye was diagnosed with lupus retinopathy accompanied by a vaso-occlusive condition. The patient underwent the first lens-sparing pars plana vitrectomy, during which a substantial neovascular membrane was removed using a vitreous cutter and forceps, followed by intraocular pan-retinal photocoagulation. Two weeks following the initial vitreous surgery, persistent vitreous rebleeding was noted, which did not resolve for 1 month, requiring a second lens-sparing pars plana vitrectomy. In the second surgery, no apparent neovascular membrane was noted and only the vitreous hemorrhage was removed.

Fig. 2.

Fundus photograph and fluorescein angiography after a 1-year discontinued follow-up period revealing extensive neovascular membrane (arrowheads) and vitreous hemorrhage (arrows) due to retinal neovascularization in the right fundus (A, C). Left fundus demonstrating no cotton wool spots, non-perfusion area, or macular edema (B, D).

The patient had regular postoperative visits for 15 years. Hydroxychloroquine was approved for SLE treatment during this period but was not introduced to the patient because of a good clinical course with low-dose oral steroids. The 15-year follow-up revealed no recurrence of neovascular membranes, vitreous hemorrhage, or macular edema in the right eye (Fig. 3-A). Furthermore, no neovascular alterations were observed in the left eye during this period (Fig. 3-B). The right and left visual acuities were 20/250 and 20/20, respectively.

Fig. 3.

Widefield fundus photograph taken 15 years after vitrectomies showing no recurrence of neovascular alterations in the right eye (A) and an absence of cotton wool spots in the left eye (B).

3. Discussion

Lupus retinopathy should be managed within the broader context of systemic immunosuppressive therapy, which typically includes corticosteroids. In our case, the patient was first diagnosed with lupus retinopathy by the ophthalmology department during the tapering phase of oral corticosteroids following intravenous methylprednisolone therapy administered by the internal medicine department. She was treated with a sub-Tenon steroid injection for macular edema and pars plana vitrectomies for the progression of retinopathy.

We report a rare progression of lupus retinopathy characterized by severe unilateral neovascular alterations and marked disparity in the initial presentation and subsequent disease course between the right and left eyes. This case report underscores three substantial clinical observations.

First, lupus retinopathy can demonstrate pronounced variations in severity between the eyes. Initial fundus examination revealed prominent cotton wool spots in the right eye but only a few spots in the left eye. A follow-up assessment after 1 year showed extensive neovascular alterations and vitreous hemorrhage in the right eye, with no signs of cotton wool spots or retinal hemorrhage in the left eye. Although lupus retinopathy typically presents with similar severity in both eyes, only a few studies have described unilateral changes.7, 8, 9 Our patient presented with unilateral vitreous hemorrhage due to severe retinal neovascularization, which was substantially different from that in previous reports. The present case suggests divergence in severity and unilateral neovascular alterations in lupus retinopathy.

Second, the clinical course, that is, improvement or exacerbation, can differ in terms of laterality. One eye may show improvement, whereas the condition in the other eye may deteriorate. To the best of our knowledge, no comprehensive review or clinical investigation has focused on this asymmetry in clinical progression. In our case, the patient discontinued ophthalmologic follow-up for a year but continued oral steroids; subsequent assessments showed retinopathy resolution in the left eye but worsening in the right eye. This discrepancy depends on the irreversible vaso-occlusive changes in the right eye. Neovascular alterations due to cytokines produced from extensive non-perfusion areas would have exceeded the improvement from oral steroid therapy. This may explain the progression of retinopathy in the right fundus, whereas cotton wool spots in the left fundus resolved.

Third, our case highlights that, even in the absence of APS, lupus retinopathy can progress to a severe neovascular state. APS is a thrombophilic state caused by antiphospholipid antibodies.¹⁰ Additionally, it is linked to severe lupus retinopathy.^4,11 Nonetheless, our patient, who tested negative for antiphospholipid antibodies and beta-2 glycoprotein, developed considerable neovascular alterations and vitreous hemorrhage attributable to extensive retinal neovascularization. This observation emphasizes that careful follow-up is necessary for patients with lupus retinopathy, even in the absence of APS.

In retrospect, a closer collaboration between ophthalmology and internal medicine might have enabled more intensive systemic therapy, potentially preventing the progression of the retinopathy. As ophthalmic management, the initial sub-Tenon steroid injection and, if no improvement in the fundus findings was observed, subsequent laser photocoagulation of non-perfusion areas were planned and explained. However, the lack of symptomatic improvement contributed to the patient's discontinuation of follow-up. Laser treatment before the interruption may have prevented progression to the neovascular state. The clinical course suggests the need for regular follow-ups, regardless of subjective symptom changes.

Furthermore, although anti-vascular endothelial growth factor therapy was not administered in the present case, several reports have suggested the potential effectiveness of intravitreal bevacizumab for treating retinal neovascularization associated with SLE-related vaso-occlusive retinopathy.^3,12,13 While the effectiveness of intravitreal bevacizumab for lupus retinopathy has yet to be fully established, it may be considered as an adjunctive treatment option in selected cases following a careful evaluation of the risks and benefits.

4. Conclusions

Herein, we describe a case of lupus retinopathy that demonstrated unilateral neovascular alterations and asymmetrical clinical progression. Although lupus retinopathy typically presents with comparable severity in both eyes, this case demonstrated unique clinical features and a distinct progression course. Additionally, our findings show that such retinopathy can advance to a severe vaso-occlusive state, even in the absence of APS. These observations indicate the importance of meticulous monitoring of lupus retinopathy with asymmetric clinical features, irrespective of APS status. This case also underscores the importance of close collaboration between internal medicine specialists and ophthalmologists in managing lupus retinopathy to optimize both systemic and ocular outcomes.

CRediT authorship contribution statement

Yusuke Takeda: Writing – review & editing, Writing – original draft, Visualization, Investigation, Data curation, Conceptualization. Kazunobu Ichikawa: Writing – review & editing, Investigation, Data curation. Masafumi Watanabe: Writing – review & editing, Supervision. Hidetoshi Yamashita: Writing – review & editing, Conceptualization. Masahiko Sugimoto: Writing – review & editing, Supervision, Conceptualization.

Patient consent

The patient provided written consent to publish this case report.

Authorship

All authors attest that they meet the ICMJE criteria for authorship.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Glossary

SLE

systemic lupus erythematosus

APS

antiphospholipid syndrome