Gordon Byrnes

A RANDOMIZED PILOT STUDY OF SYSTEMIC IMMUNOSUPPRESSION IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH CHOROIDAL NEOVASCULARIZATION

Background: Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. Methods: This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results: The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion: These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated.

Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization.

Purpose:  To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis‐associated choroidal/retinal neovascularization.

Intravitreal Methotrexate Resistance in a Patient with Primary Intraocular Lymphoma

Purpose: To describe the clinical course of a patient with multiple recurrences of primary intraocular lymphoma (PIOL). Design: Interventional case report, Methods: Retrospective chart review. Results: A 57-year-old female treated with multiple intravitreal methotrexate injections became refractory to intravitreal methotrexate after a year. Lymphoma cells evaluated using immunocytochemistry and confocal microscopy showed aberrant multidrug resistance-related protein (MRP) and decreased reduced folate carrier (RFC) and folate binding protein (FBP) expression compared to PIOL cells from another patient clinically responsive to methotrexate. Conclusions: This case suggests that alterations in the transport of methotrexate across the cell membrane might contribute to resistance following repeated intravitreal injections.

Recalcitrant Granulomatous Sclerouveitis in a Patient with Granulomatous ANCA-associated Vasculitis

Purpose: To report an unusual case of granulomatous sclerochoroiditis. Design: Interventional case report. Methods: A patient with ANCA-associated granulomatous vasculitis presented with nodular necrotizing scleritis, which was recalcitrant to multiple systemic immunosuppressive therapies and progressed to a blind painful eye, which was enucleated. Results: Histopathology revealed extensive occlusive vasculitis, diffuse T- and B- cellular infiltration, and lymphoid granulomatous formation. Enhanced MHC class II antigens, adhesion molecules, and Fas (CD95) and FasL (CD95L) were detected in the lesion. Conclusion: Granulomatous sclerochoroiditis with aggressive immune reaction can be a complication of ANCA-associated granulomatous vasculitis.

Fluorescein angiography in the progressive outer retinal necrosis syndrome.

Purpose: Progressive outer retinal necrosis syndrome is a devastating retinopathy seen primarily in patients with acquired immune deficiency syndrome. To provide additional details of the pathogenesis of this disease, the authors describe the evolution of clinical and fluorescein angiographic changes during the course of progressive outer retinal necrosis syndrome. Methods: The authors performed serial clinical examinations, fundus photography, and fluorescein angiography in a patient with acquired immune deficiency syndrome with progressive outer retinal necrosis syndrome. Clinical and fluorescein angiographic findings were correlated to provide detailed sequential analysis of the pathologic changes occurring during the course of this disorder. Results: The angiographic changes seen during the various stages of the disease consisted of zonal microvascular alterations, retinal pigment epithelium (RPE) destruction, and choroidal leakage. Retinal damage was correlated closely with regions of choroidal leakage and was clinically evident as outer retinal whitening. Disease reactivation occurred as a prominent brush-fire border of intense leakage involving the retina, RPE, and choroid. Extensive damage to the retinal vasculature and RPE was noted in the wake of clinical infection. Conclusions: The angiographic findings in our patient demonstrate that the progressive outer retinal necrosis syndrome is a retinochoroiditis that involves the full thickness of retina as well as the RPE and choroid. The inflammatory changes seen throughout the course of this disease correlate with the histopathologic patterns reported to date.