Comparison of Novel Volumetric Microperimetry Metrics in Intermediate Age-Related Macular Degeneration: PINNACLE Study Report 3

PURPOSE: To investigate and compare novel volumetric microperimetry (MP)–derived metrics in intermediate age-related macular degeneration (iAMD), as current MP metrics show high variability and low sensitivity. METHODS: This is a cross-sectional analysis of microperimetry baseline data from the multicenter, prospective PINNACLE study (ClinicalTrials.gov NCT04269304). The Visual Field Modeling and Analysis (VFMA) software and an open-source implementation (OSI) were applied to calculate MP-derived hill-of-vison (HOV) surface plots and the total volume (VTOT) beneath the plots. Bland–Altman plots were used for methodologic comparison, and the association of retinal sensitivity metrics with explanatory variables was tested with mixed-effects models. RESULTS: In total, 247 eyes of 189 participants (75 ± 7.3 years) were included in the analysis. The VTOT output of VFMA and OSI exhibited a significant difference (P < 0.0001). VFMA yielded slightly higher coefficients of determination than OSI and mean sensitivity (MS) in univariable and multivariable modeling, for example, in association with low-luminance visual acuity (LLVA) (marginal R(2)/conditional R(2): VFMA 0.171/0.771, OSI 0.162/0.765, MS 0.133/0.755). In the multivariable analysis, LLVA was the only demonstrable predictor of VFMA VTOT (t-value, P-value: −7.5, <0.001) and MS (−6.5, <0.001). CONCLUSIONS: The HOV-derived metric of VTOT exhibits favorable characteristics compared to MS in evaluating retinal sensitivity. The output of VFMA and OSI is not exactly interchangeable in this cross-sectional analysis. Longitudinal analysis is necessary to assess their performance in ability-to-detect change. TRANSLATIONAL RELEVANCE: This study explores new volumetric MP endpoints for future application in therapeutic trials in iAMD and reports specific characteristics of the available HOV software applications.