The shallow irregular RPE elevation (SIRE) sign—a derivative of the double-layer sign (DLS)—has consistently agreed with the presence of exudative macular neovascularization (eMNV) detected by OCT-A in previous studies, but it remains to be determined if SIRE provides any added benefit for predicting the onset of exudation compared with the DLS. In a new study, SD-OCT images were re-analyzed for the DLS and SIRE sign, and researchers found that while the DLS is a highly sensitive predictor of progression to eMNV, the use of SIRE does not improve predictability.

SD-OCT imaging shows the highest rate of progression was in eyes with the double layer sign, while shallow irregular RPE elevation—a derivative of DLS—does not increase hazard of progression.

SD-OCT imaging shows the highest rate of progression was in eyes with the double layer sign, while shallow irregular RPE elevation—a derivative of DLS—does not increase hazard of progression. Photo: Eric Dillinger, OD. Click image to enlarge.

Of the 459 eyes included, 268 had irregular elevation of the RPE in which 101 were DLS-like and 51 of these also fulfilled criteria for SIRE. SD-OCT volume scans of study eyes were graded for irregular elevation, length and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the irregular elevation were classified as exhibiting the DLS. Eyes with the double-layer sign where the length of separation between RPE and Bruch’s was equal or exceeded 1000μm in length and less than 100μm in height were sub-classified as SIRE.

When study eyes were grouped by presence of irregular elevation, double-layer sign and SIRE, “we found that all three SD-OCT biomarkers increased the risk of progression to eMNV with the highest rate of progression in eyes with DLS,” the authors explained in their paper for Ophthalmology Retina. The proportions rose from 13% for eyes without any of the aforementioned SD-OCT biomarkers, to 29% when irregular elevation was present and increased further to 41% when the DLS was present and remained around this level (37%) when the criteria for SIRE were fulfilled. “These findings support the view that the dimensions of the DLS are less important in terms of the predictability of progression to eMNV,” they wrote.

 “Our study confirmed on a pragmatic level that eyes exhibiting the DLS have a four times greater hazard of progression to eMNV over three years,” the authors further explained. “The presence of SIRE, a derivative of the DLS, carried a similar risk of progression to eMNV and did not increase predictive ability.”

The sensitivity analyses confirmed that progression to neovascularization was significantly faster for DLS and/or SIRE compared to eyes with irregular elevation only. Irregularity by itself also increased the risk of progression to eMNV, though the hazard ratios were lower compared. Because the 75% survival probability dropped from 29 months in eyes with irregular elevation to 19 months when DLS is present, “we believe that it would prudent to review (individuals) who show these very high-risk characteristics on a six-month basis if not attending more frequently,” the authors suggested.

Because irregular elevation in itself carried an increased risk of progression to exudative macular neovascularization, “we recommend that eyes with any elevation of the RPE are monitored. However, as the presence of the DLS elevates this risk more than twofold, we especially feel that such patients merit closer monitoring with high-resolution imaging, particularly with OCT-A,” the authors concluded.

Csincsik L, Muldrew KA, Bettiol A, et al. The double layer sign is highly predictive of progression to exudation in age-related macular degeneration. Ophthalmology Retina. October 9, 2023. [Epub ahead of print.]