Central subfield thickness (CST) is a common secondary endpoint on studies of anti-VEGF in diabetic macular edema (DME), but it’s not the most robust biomarker. Changes in CST are known to have low correlations with visual acuity in these patients. Nevertheless, CST is often used because other OCT biomarkers such as disorganization of the retinal layers or loss of the ellipsoid zone, which are associated with visual acuity in DME, are challenging to identify in any automated way.

A recent study investigated the impact of CST fluctuations on DME patients’ visual acuity with anti-VEGF treatment. The team found that large fluctuations were associated with worse visual acuity outcomes.

The cohort study included 1,197 eyes from the DRCR.net Protocols T and V. The researchers recorded the CST standard deviations for all patients to quantify fluctuations and grouped the participants by quartiles.

The researchers identified significant visual acuity differences among CST standard deviation quartiles for both Protocols after adjusting for mean baseline visual acuity, baseline CST, lens status, hemoglobin A1c and treatment arm.

Protocol T findings:

  • At week 52, the difference between the first and fourth quartiles was -1.61 ETDRS letters.
  • At week 104, the difference was -3.59 letters.

Protocol V findings:

  • At week 52, the difference between the first and fourth quartiles was -3.04 letters.
  • At week 104, the difference was -2.35 letters.

The study authors noted that single-visit CST measurements in patients with diabetic retinopathy aren’t good surrogates for visual acuity due to the “inability to assess the foveal vascularity and retinal layer architecture.” The researchers pointed out that previous studies suggested a low correlation with CST changes and visual acuity, but those studies examined only the delta from one time point to the next.

“Utilization of standard deviation enables monitoring of fluid shifts over time,” they explained. “The lowest quartile of eyes had less fluctuation in CST, perhaps reflecting better disease control with the given regimen, compared with the highest quartile, which had more fluctuations in CST and perhaps worse disease control.”

Greater fluctuation in CST over time measured by standard deviation was strongly associated with worse visual acuity in Protocols T and V, the researchers concluded. Analyzing CST fluctuations on OCT “may provide better insight into visual acuity outcomes compared with measuring the difference in CST at two time points or looking at a single CST measurement which may not reflect disease control as well,” they wrote. They added that sustained-release therapeutic options will likely lead to less fluctuation.

Starr MR, Salabati M, Mahmoudzadeh R, et al. Fluctuations in central subfield thickness associated with worse visual outcomes in patients with diabetic macular edema in clinical trial setting. Am J Ophthalmol. 2021. [Epub ahead of print].