Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and treatment

Abstract

Choroidal neovascular membrane (CNVM) formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII). The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.

Phase IIb clinical trial of ranibizumab for the treatment of uveitic and idiopathic choroidal neovascular membranes

“…Before anti-VEGFs were available, corticosteroids were the first-line treatment for iCNV and, in particular, corticosteroids in addition to PDT were more effective than PDT alone 25. Similarly, the combination of high dose systemic steroids in combination with mycophenolate mofetil showed good control of iCNV, with improved VA and stabilisation of the CNV complex size 6.…”

Risk of Choroidal Neovascularization among the Uveitides

“…A review by Dhingra et al concerning the formation of choroidal neovascular membranes in posterior segment intraocular inflammation identified leukocytes and chronic chorioretinal inflammation as being critical for the development of CNV 15 . Activated macrophages and other inflammatory cells secrete enzymes that damage cells and cause degradation in Bruch’s membrane, and the cytokines released by these inflammatory cells may promote the growth of CNV through the break in Bruch’s membrane and into the sub-RPE space, potentially leading to edema, exudation, hemorrhages, and fibrosis which result in profound central vision loss 15-17 . The salutary effects of anti-inflammatory and immunosuppressive agents for the treatment of CNV provides further support for an inflammatory contribution to pathogenesis.…”

“…For example, in the pre-vascular endothelial growth factor (VEGF) inhibitor era, corticosteroids had been proposed as a first-line approach 18 based on their inhibitory action on inflammatory cells and subsequently the suppression of pro-angiogenic mediators, as well as their ability to decrease vascular permeability and prevent vascular budding 15, 18 . In addition, there has been some evidence suggesting that adding corticosteroids to photodynamic therapy (PDT) is more effective than PDT alone in inflammatory CNV 15 . These considerations and our results suggest that controlling inflammation is not only indicated for treating the uveitis itself, but also for preventing and/or treating CNV.…”

The role of imaging in the diagnosis and management of uveitis

“…The development of CNV results from an inflammatory-driven angiogenic response in the setting of disruption of the Bruch's membrane-RPE complex [75,76]. Underlying choroidal vessels associated with areas of choroiditis may decompensate, causing serous exudation, serous retinal detachment and CNV.…”