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Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). In the last two decades, complement activity has been the focus of intense investigation in AMD pathogenesis, leading to the development of novel therapeutics for the treatment of atrophic AMD. This Review outlines recent advances and challenges, highlighting therapeutic approaches that have advanced to clinical trials, as well as providing a general overview of the complement system in the posterior segment of the eye and selected ocular diseases., Introduction Investigation into ocular disease must account for the eye's unique relationship with the systemic immune system. The eye is an immune-privileged organ, meaning it can tolerate novel antigens without [...]

Abnormal angiogenesis plays a key role in diseases of aging such as heart disease, certain cancers, and eye diseases including age-related macular degeneration. Macrophages have been shown previously to be [...]

BACKGROUND. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S. METHODS. Eleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical coherence tomography central subfield thickness (CST) at baseline, 1 year, and 2 years. A mixed repeated-measures analysis was performed to assess the progression rates and changes from baseline. RESULTS. Eleven participants received crizanlizumab infusions. All of the participants tolerated crizanlizumab well, with 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms. The change in total retinal nonperfusion was 7.22% [4.47, 9.97] in year 1 and –0.69% [–4.06, 2.68] in year 2 (P < 0.001). In the mid periphery, the change in nonperfusion was 10.6% [5.1, 16.1] in year 1 and –0.68% [–3.98, 5.35] in year 2 (P < 0.01), demonstrating a reduction in progression of nonperfusion in the second year of treatment. Visual acuity, IOP, and CST remained stable. CONCLUSION. Crizanlizumab has an acceptable safety profile. These results show promising potential for examining crizanlizumab in larger studies of RVCL-S and similar small-vessel diseases and for using the retina as a biomarker for systemic disease. [ABSTRACT FROM AUTHOR]