Double-Layer Sign on OCT has limitation in Detecting Non-Exudative Macular Neovascularization: JAMA
Researchers have found in a prospective study of 550 cases that the double-layer sign on optical coherence tomography (OCT), commonly used in the fellow eye of patients with unilateral neovascular age-related macular degeneration, is an unreliable marker for detecting non-exudative macular neovascularization. The findings emphasize that clinicians should not rely solely on OCT features, but instead combine OCT with OCT angiography for more accurate diagnosis. Additionally, experts highlight the importance of individualized interpretation of imaging data, tailoring diagnostic approaches to each patient’s clinical context. The study was published in JAMA Ophthalmology by Sridevi T. and colleagues.
In the beginning, the research involved a screening process conducted on 862 patients who were undergoing treatment with anti-VEGF drugs due to exudative AMD in their first eye. For the main analyses, researchers selected only 550 subjects who received both structural OCT and OCT-A tests within 30 days from the first dose of anti-VEGF therapy. The mean age of all patients was 78.0 years, with the following demographic statistics: 57.3% of women (n=315) and 42.7% men (n=235). By choosing the so-called "fellow eye," which is characterized by the absence of exudative lesions at the early stages, the scientists tried to determine the very early signs of development of the disease. Data analyses using logistic regression were performed strictly between July and October 2025.
Key findings:
- Out of the total 550 eyes used for analysis, 112 eyes (20.4%) showed DLS through structural OCT.
- Nevertheless, out of all the eyes analyzed, the neMNV could be detected through OCT-A only in 47 eyes, which is equal to 8.5% of the total eyes.
- In the case of eyes that showed DLS, the percentage of eyes that showed neMNV is very low.
- Out of 112 eyes that had a DLS, only 42 eyes had neMNV, which makes the prevalence only 40%.
- It is found that the thickness of the DLS played a key role in predicting neMNV.
- Eyes having thick DLS had a higher prevalence of neMNV of 48% (36 eyes) compared to thin DLS of only 16.2% (6 eyes).
In summary, this prospective investigation provides compelling evidence that the DLS is an unreliable surrogate marker of nonexudative macular neovascularization in unilateral AMD patients. Although about one out of five fellow eyes demonstrated a DLS, only a small number of these eyes harbored the actual vascular abnormality of neMNV. Thus, the findings emphasize the importance of using OCT-A in lieu of OCT to avoid false-positive conclusions based on morphologic signs alone.
Reference:
Thottarath S, Gurudas S, Kubravi S, et al. Nonexudative Macular Neovascularization in Age-Related Macular Degeneration. JAMA Ophthalmol. Published online April 09, 2026. doi:10.1001/jamaophthalmol.2026.0459
