Identifying Imaging Predictors of Intermediate Age-Related Macular Degeneration Progression

Abstract

Purpose Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting individual risk is advantageous for programing timely and effective treatment and for patient stratification into future clinical trials. Methods We conducted a prospective and noninterventional study following patients with iAMD for 24 months. Optical coherence tomography parameters related with drusen, hyper-reflective foci (HRF), presence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and ellipsoid zone (EZ) status were explored at the baseline. Patients were reclassified at the end of the follow-up period and divided according to their progression. A risk prediction model for progression to late AMD was developed. Results A total of 135 patients were enrolled in the study and 30.4% developed late disease. A multivariate logistic regression model was created using those optical coherence tomography parameters, further optimized by backward feature elimination. Parameters offering the best fit in prediction progression were presence of iRORA, EZ status, drusen area and presence of HRF. iRORA is the feature that provides a higher probability of developing late AMD (odds ratio, 12.91; P = 0.000), followed by EZ disruption status (odds ratio, 3.54; P = 0.0018). The area under the receiver operating characteristic curve calculated for the testing set was 0.77 (95% confidence interval, 0.56–0.98). Conclusions The combination of iRORA and EZ disruption constitute a high risk of progression to complete RORA within 2 years. Translational Relevance We propose a practical and useful model to help clinicians in their daily practice in predicting individual progression to advanced AMD.

Optical coherence tomography biomarkers in early and intermediate age‐related macular degeneration: A clinical guide

“…Recently iRORA has been proposed as a biomarker of intermediate AMD, however, as Wu et al suggested, iRORA is also a precursor of cRORA and therefore a predictive factor for GA development 57 . Furthermore, Flores et al identified iRORA as the factor with the higher probability of developing advanced AMD (OR 12.91) 58 …”

Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers

“…In general, standard OCT is used for the identification of iRORA lesions; nevertheless, high-resolution OCT has been superior in the detection and classification of the atrophic lesions, enhancing the assessment reliability. iRORA is a noteworthy OCT biomarker as these lesions are predecessors for GA and a high-risk progression factor to the advanced stages of AMD [128]. Another relevant aspect to note is that the term "nascent GA" can be used when iRORA lesions are present but there is no association with previous or present signs of macular neovascularization [152].…”

“…The disruption of EZ is another OCT parameter which has been linked to the progression of AMD to advanced stages [11,64,99]. There is 2.5-fold risk increase of developing advanced stages of AMD in patients that present with EZ disruption compared to those without it [128]. EZ changes have been noticed as early as 4 years before GA onset [85].…”

“…In a multivariate analysis model, some results even suggest that EZ disruption together with iRORA are among the best progression predictor biomarkers. When both OCT abnormalities are present, there is a high risk of advancement to cRORA within the next two years [128]. EZ disruption has been recounted as the precursor for the succeeding RPE atrophy in patients with GA [1].…”