Search

Purpose To determine, using an aptamer-based technology in patients with intermediate age-related macular degeneration (AMD), (1) if there is a difference in plasma levels of 4979 proteins in patients with and without reticular pseudodrusen (RPD), and (2) if plasma levels of proteins are related to time to conversion to advanced AMD. Methods Patients with intermediate AMD and RPD were identified from an AMD registry. Relative concentrations of each protein were log (base 2) transformed and compared between patients with and without RPD using linear regression. A Cox proportional hazards survival model was fit to each aptamer to quantify associations with time to conversion. A pathway analysis was conducted in converters versus non-converters using the Reactome database. Results Of the 109 intermediate AMD patients, 39 had bilateral RPD (36%). Two proteins, TCL1A and CNDP1, were lower in patients in the intermediate AMD group with RPD. Twenty-one patients converted to advanced AMD with a median time to conversion of 25.2 months (range, 2.3-48.5 months) and median follow-up time in non-converters of 26.4 months (range, 0.03-49.7 months). Several proteins (lysozyme C, TFF3, RNAS6, and SAP3) distinguished patients who converted from those who did not convert to advanced AMD. The top conversion pathways included tumor necrosis factors bind their physiological receptors, digestion and absorption, signaling by activin, and signaling by TGF-β family members. Conclusions We identified a protein signature related to RPD, as well as to conversion to advanced AMD. The pathway analysis suggests that dysfunction of critical systemic pathways may have links to conversion to advanced AMD. Translational relevance Biomarkers identified in plasma likely reflect systemic alterations in protein expression in patients with intermediate AMD.

ObjectiveSystemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD.Methods and analysisLevels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma.Results109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD.ConclusionsLevels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

BACKGROUND AND OBJECTIVE: To compare fundus autofluorescence (FAF) imaging via fundus camera (FC) and confocal scanning laser ophthalmoscope (cSLO). PATIENTS AND METHODS: FAF images were obtained with a digital FC (530 to 580 nm excitation) and a cSLO (488 nm excitation). Two authors evaluated correlation of autofluorescence pattern, atrophic lesion size, and image quality between the two devices. RESULTS: In 120 eyes, the autofluorescence pattern correlated in 86% of lesions. By lesion subtype, correlation rates were 100% in hemorrhage, 97% in geographic atrophy, 82% in flecks, 75% in drusen, 70% in exudates, 67% in pigment epithelial detachment, 50% in fibrous scars, and 33% in macular hole. The mean lesion size in geographic atrophy was 4.57 ± 2.3 mm 2 via cSLO and 3.81 ± 1.94 mm 2 via FC ( P < .0001). Image quality favored cSLO in 71 eyes. CONCLUSION: FAF images were highly correlated between the FC and cSLO. Differences between the two devices revealed contrasts. Multiple image capture and confocal optics yielded higher image contrast with the cSLO, although acquisition and exposure time was longer. [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:536–543.]