Systematic review of extensive macular atrophy with pseudodrusen reports visual acuity decline and atrophy progression

This publication is a systematic review and meta-analysis of observational studies on extensive macular atrophy with pseudodrusen (EMAP). The analysis synthesized data from 1096 eyes across patient cohorts, though the specific clinical settings were not reported. The population consisted of patients diagnosed with EMAP, and the intervention was a review of clinical and multimodal imaging features. No specific comparator was defined for this synthesis.

The primary analysis focused on disease progression metrics. For best-corrected visual acuity (BCVA) at diagnosis, the pooled mean was 0.62 logMAR, with a 95% CI of 0.47 to 0.76 and substantial heterogeneity (I² = 95.6%). Over a mean follow-up of 2.1 years, BCVA worsened by a mean of 0.41 logMAR, which corresponds to a loss of 3 lines of vision. Progression of macular atrophy area increased by an average of 8.3 mm² over a mean follow-up of 3.9 years, with a 95% CI of 3 to 3.57 and moderate heterogeneity (I² = 69.8%).

Key secondary outcomes were also synthesized. Central choroidal thickness on OCT was reported with a mean of 135.8, with a 95% CI of 113.3 to 158.3 and high heterogeneity (I² = 94.4%). Electroretinography findings indicated rod dysfunction with an abnormal photopic response. A notable secondary finding was a reported rheumatic fever prevalence of 89% of patients across Brazilian cohorts, with a 95% CI of 83.2 to 93% and no heterogeneity (I² = 0%).

Safety and tolerability data were not reported in the source evidence. The review did not provide information on adverse events, serious adverse events, or treatment discontinuations. This absence of safety data is a significant limitation for clinical application.

These results can be compared to prior landmark studies in age-related macular degeneration, though direct comparison is limited by the specific focus on EMAP and the observational nature of the included studies. The high heterogeneity (I² up to 95.6%) suggests considerable variability across the included studies, which may affect the reliability of the pooled estimates.

Key methodological limitations include the heterogeneity and biases inherent to non-randomized studies, as well as inconsistencies in results and hypothesized associations. The review is based on observational data, which limits causal inference. The certainty of the evidence is reduced by these factors.

The clinical implications are that identifying clinical and imaging biomarkers is critical to improve EMAP diagnosis and guide future research. However, the observational nature of the evidence means these findings should inform hypothesis generation rather than direct practice decisions. The results highlight the progressive nature of EMAP but do not support specific therapeutic interventions.

Unanswered questions include the need for randomized trials to establish causality, the role of specific imaging biomarkers in prognosis, and the management strategies for slowing disease progression. The association with rheumatic fever requires further investigation to determine its clinical relevance.