Mechanisms of FH Protection Against Neovascular AMD.

A common allele (402H) of the complement factor H (FH) gene is the major risk factor for age-related macular degeneration (AMD), the leading cause of blindness in the elderly population. Development and progression of AMD involves vascular and inflammatory components partly by deregulation of the alternative pathway of the complement system (AP). The loss of central vision results from atrophy and/or from abnormal neovascularization arising from the choroid. The functional link between FH, the main inhibitor of AP, and choroidal neovascularization (CNV) in AMD remains unclear. In a murine model of CNV used as a model for neovascular AMD (nAMD), intraocular human recombinant FH (recFH) reduced CNV as efficiently as currently used anti-VEGF (vascular endothelial growth factor) antibody, decreasing deposition of C3 cleavage fragments, membrane attack complex (MAC), and microglia/macrophage recruitment markers in the CNV lesion site. In sharp contrast, recFH carrying the H402 risk variant had no effect on CNV indicating a causal link to disease etiology. Only the recFH NTal region (recFH1-7), containing the CCPs1-4 C3-convertase inhibition domains and the CCP7 binding domain, exerted all differential biological effects. The CTal region (recFH7-20) containing the CCP7 and CCPs19-20 binding domains was antiangiogenic but did not reduce the microglia/macrophage recruitment. The antiangiogenic effect of both recFH1-20 and recFH-CCP7-20 resulted from thrombospondin-1 (TSP-1) upregulation independently of the C3 cleavage fragments generation. This study provides insight on the mechanistic role of FH in nAMD and invites to reconsider its therapeutic potential.

Three Different Optical Coherence Tomography Angiography Measurement Methods for Assessing Capillary Density Changes in Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR) progression using three previously published methods: binarization, skeletonization, and automated flow density (AFD). PATIENTS AND METHODS: Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes imaged using OCTA. The macular CD at each stage of DR was assessed using the three methods and were compared to control eyes. RESULTS: AFD was the only method that detected differences between controls and severe nonproliferative DR eyes. The three methods showed a significant difference in CD between controls and eyes with proliferative DR, except for the "fovea" area. CONCLUSION: Only one of the three methods allowed for the detection of changes from the normal capillary density as early as at the "severe nonproliferative DR" stage due to several refinements from the basic technique. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:378-384.].

Efficacy of dexamethasone intravitreal implant for the treatment of diabetic macular edema.

PURPOSE: To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). METHODS: This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (gt;24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. RESULTS: Preoperative mean CMT was 559 ± 111 µm and decreased to 338 ± 84 and 477 ± 140 µm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (p<0.0001), a recurrence of the macular edema was observed 4 months after injection in 79% of eyes. Mean BCVA improvement (logMAR) was 0.13 ± 0.18 (p<0.0001) and 0.07 ± 0.21 (p = 0.049) 2 and 4 months after injection, respectively, without significant difference between vitrectomized and nonvitrectomized eyes. Eight eyes (21%) developed reversible increase in IOP 2 months after injection. CONCLUSIONS: Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.