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Purpose: The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD)., Methods: We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 individuals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency., Results: Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003)., Conclusions: Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.

Purpose: To evaluate the potential of psychophysical assessments of retinal function to provide diagnostic biomarkers of early age-related macular degeneration (AMD)., Methods: Unilateral visual function was assessed in 221 participants (72.86 ± 9.94 years; 67% women) with early AMD (visual acuity better than 20/60) and 109 controls (73.07 ± 10.32 years; 65% women). Psychophysical assessment included steady state thresholds (4- and 14-Hz flicker and red and blue color) and dynamic tests (photostress recovery [PSR] and dark adaptation [DA]). All test parameters were compared in terms of their diagnostic capacity (sensitivity and specificity), reproducibility, and clinical applicability (test duration and participant's perception of test difficulty). AMD status was determined by digital photography, according to the International Classification and Grading System., Results: All functional measurements were significantly worse, on average, in the AMD group than in the control group (P < 0.001). Static and dynamic parameters showed weak correlations (range, 0.003-0.225). Rod recovery in DA and cone recovery in PSR had the best diagnostic capacity (area under curve [AUC], receiver operating characteristic [ROC] analysis, 0.93 ± 0.016 and 0.85 ± 0.021, respectively). Considering diagnostic capacity together with test reproducibility and clinical applicability, the 14-Hz flicker gave the best outcome, followed by PSR. Combination of these two tests detected 71% of abnormal early AMD cases., Conclusions: All the visual function tests had good diagnostic capacity. Combination of the 14-Hz flicker thresholds and dynamics of the PSR test provided optimal quantitative assessment of retinal function in early AMD, suggesting that this set is a potentially useful clinical tool for following progression of early AMD and assessing the efficacy of interventions.

Purpose: Age-related macular degeneration (AMD) can be considered as a chronic low-grade systemic inflammatory disease. This study was undertaken to test the associations of AMD with the urinary proinflammatory cytokines transforming growth factor (TGF)-β1, macrophage chemoattractant protein (MCP)-1 and C3a-desArg, as potential noninvasive biomarkers for monitoring AMD., Methods: A cross-sectional study of 103 AMD cases, comprising early AMD (n = 51), geographic atrophy (GA; n = 19), or choroidal neovascularization (CNV; 33), and 54 unrelated controls, aged 73 ± 9 years, who attended the Royal Victorian Eye and Ear Hospital and private practice in Victoria, Australia. AMD status was determined from the bilateral retinal digital photographs and through angiography and optical coherence tomography images when confirmation of CNV was needed. Serum and urine cytokine levels were measured by immunoassay and the rs1061170 (Y402H) single-nucleotide polymorphism of the complement factor H (CFH) gene was determined., Results: Multivariate logistic regression analyses demonstrated significant associations of urinary TGF-β1 levels (odds ratio [95% confidence interval]: OR = 1.24 [1.02-1.50]; P < 0.031) and MCP-1 levels (OR = 1.07 [1.02-1.12]; P < 0.008), in early AMD, and also MCP-1 levels with GA (OR = 1.10 [1.03-1.17]; P < 0.003). There was no correlation between urinary and serum cytokine levels. Individuals with one or more copies of the C allele (Y402H) were 2.5 times more likely to have urinary MCP-1 above median levels (P < 0.040)., Conclusions: This study demonstrates a novel finding of an association between elevated urinary cytokines TGF-β1 and MCP-1 and AMD. Further development of a urinary biomarker profile could provide a practical tool for detection of early AMD, progression monitoring, and assessment of treatment efficacy.