Analyzing and Predicting Visual Acuity Outcomes of Anti-VEGF Therapy by a Longitudinal Mixed Effects Model of Imaging and Clinical Data.

Abstract

We develop a longitudinal statistical model describing best-corrected visual acuity (BCVA) changes in anti-VEGF therapy in relation to imaging data, and predict the future BCVA outcome for individual patients by combining population-wide trends and initial subject-specific time points. Automatic segmentation algorithms were used to measure intraretinal (IRF) and subretinal (SRF) fluid volume on monthly spectral-domain optical coherence tomography scans of eyes with central retinal vein occlusion (CRVO) receiving standardized anti-VEGF treatment. The trajectory of BCVA over time was modeled as a multivariable repeated-measure mixed-effects regression model including fluid volumes as covariates. Subject-specific BCVA trajectories and final treatment outcomes were predicted using a population-wide model and individual observations from early follow-up. A total of 193 eyes (one per patient, 12-month follow-up, 2420 visits) were analyzed. The population-wide mixed model revealed that the impact of fluid on BCVA is highest for IRF in the central millimeter around the fovea, with -31.17 letters/mm3 (95% confidence interval [CI], -39.70 to -23.32), followed by SRF in the central millimeter, with -17.50 letters/mm3 (-31.17 to -4.60) and by IRF in the parafovea, with -2.87 letters/mm3 (-4.71 to -0.44). The influence of SRF in the parafoveal area was -1.24 letters/mm3 (-3.37-1.05). The conditional R2 of the model, including subject-specific deviations, was 0.887. The marginal R2 considering the population-wide trend and fluid changes was 0.109. BCVA at 1 year could be predicted for an individual patient after three visits with a mean absolute error of six letters and a predicted R2 of 0.658 using imaging information. The mixed-effects model revealed that retinal fluid volumes and population-wide trend only explains a small proportion of the variation in BCVA. Individual BCVA outcomes after 1 year could be predicted from initial BCVA and fluid measurements combined with the population-wide model. Accounting for fluid in the predictive model increased prediction accuracy.