Prognostic Value of Retinal Layers in Comparison with Other Risk Factors for Conversion of Intermediate Age-related Macular Degeneration

Abstract

To analyze longitudinal thickness changes of retinal layers in comparison with established risk factors in eyes with age-related macular degeneration (AMD) with regard to their prognostic value for conversion into advanced AMD stages. Prospective, longitudinal natural history study. Ninety-one eyes of 91 patients with AMD (73.3±7.3 years; 62 female patients [50.4%]) of the Molecular Diagnostic of Age-related Macular Degeneration (MODIAMD) study without exudative or nonexudative late-stage AMD in the study eye at baseline. At each annual follow-up visit, all subjects underwent ophthalmic examination with assessment of best-corrected visual acuity (BCVA) and retinal imaging, including spectral-domain OCT (SD-OCT), over a study period of 6 years. To analyze longitudinal thickness changes of retinal layers in comparison with established risk factors in eyes with age-related macular degeneration (AMD) with regard to their prognostic value for conversion into advanced AMD stages. Qualitative structural AMD features and SD-OCT-based quantitative thickness changes of different retinal layers, such as the retinal pigment epithelium-drusen complex (RPEDC), were assessed by multimodal imaging. Their prognostic relevance regarding disease conversion was determined using Cox regression (cloglog link function). In the multivariable analysis, the presence of focal hyperpigmentation, almost reaching statistical significance, showed the strongest effect regarding the development of nonexudative late-stage AMD (hazard ratio [HR], 5.88; 95% confidence interval [CI], 0.69-50.2; P= 0.052) followed by the presence of refractile drusen (HR, 4.82; 95% CI, 1.33-17.44; P= 0.0164). A thickening of the RPEDC was the only assessed retinal layer that exhibited a significant effect on the development of nonexudative advanced AMD (HR, 1.03; 95% CI, 1.0-1.07; P= 0.0393), whereas no association was observable for the other retinal layers. Neither qualitative nor quantitative markers were significant predictors for the development of exudative late-stage AMD (P > 0.05). The results indicate that the development of both exudative and nonexudative AMD is associated with distinct prognostic features. However, compared with the assessment of qualitative AMD features, the quantification of retinal layers on average across the central retina had less prognostic impact. Further studies are needed to identify and validate robust biomarkers in early AMD stages.