Cracking nAMD’s code: interface traction, a unified double-layer sign, and photoreceptor revival on OCT/OCTA

Dear Editor,

We read Crincoli et al.’s timely review of OCT/OCTA biomarkers in neovascular AMD (nAMD) with great interest [1]. While the authors catalog many established and emerging markers, several interpretative gaps remain. We offer three complementary refinements.

First, the vitreoretinal interface warrants closer attention. The review notes conflicting data on whether complete posterior vitreous detachment (PVD) modifies anti-VEGF outcomes. Recent ultra-widefield (UWF) OCT shows PVD (stages 3–4) is markedly more common in AMD than in age-matched controls, implying that early vitreomacular traction (VMT) may promote neovascularization [2]. Because widefield scans detect peripheral detachments invisible on conventional OCT, routine UWF or swept-source imaging could classify eyes by VMT/PVD status and individualize surveillance or early intervention.

Second, the “double-layer sign” (DLS) should be standardized and used prognostically. Expert graders detect subclinical macular neovascularization via the DLS with ~88% accuracy, yet new evidence shows prognostic power as well: an irregular RPE elevation with heterogeneous reflectivity tripled the three-year risk of exudation (hazard ratio ≈ 3.4) [3]. Sivaprasad et al. underline that multiple labels (e.g., shallow irregular RPE elevation) describe the same feature, and that its morphology varies widely [4]. We therefore propose unified DLS criteria—quantitative length/height thresholds or automated algorithms—and systematic reporting in predictive models.

Third, dynamic metrics of the outer retina deserve emphasis. Baseline outer-nuclear-layer (ONL) thinning predicts conversion, but recent data indicate that ONL thickening during therapy is equally informative. Lee et al. demonstrated that eyes whose foveal ONL recovered significantly after the loading phase achieved superior one-year visual acuity [5]. Tracking ONL change, not merely baseline thickness, could thus gauge photoreceptor salvage and guide retreatment frequency.

In summary, incorporating advanced vitreoretinal interface imaging to clarify PVD/VMT effects, adopting rigorously defined DLS parameters as conversion biomarkers, and monitoring ONL recovery as a dynamic prognostic sign can enhance the precision-imaging paradigm outlined by Crincoli et al. These updates, grounded in recent literature, strengthen the clinical utility of OCT/OCTA biomarkers in nAMD.

Author contributions

All authors participated in the study’s conception, design, and interpretation of results. KB and YZ jointly conceived the project, designed the study, acquired and analyzed the data, and drafted the manuscript; they contributed equally and share first authorship. XM supervised the work, provided critical revisions for important intellectual content, and, as the corresponding author, approved the final version for publication.

Funding

This work was funded by financial support from the National Natural Science Foundation of China, awarded to XM, under grant number 81271022.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Competing interests

The authors declare no competing interests.