Deepak Sambhara, MD: Impact of CRT on Aflibercept 8 mg Outcomes in DME

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Deepak Sambhara, MD, describes the influence of baseline central retinal thickness on visual outcomes in a post-hoc analysis of the PHOTON study.

Aflibercept 8 mg achieved meaningful improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) across baseline quartiles in eyes with diabetic macular edema (DME), according to a posthoc analysis of the phase 2/3 PHOTON trial.

Presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting, eyes with the thickest baseline CRT experienced numerically less fluid reaccumulation at 8 weeks after the last initial monthly dose of aflibercept 8 mg versus 2 mg aflibercept, indicating its durability.

In an interview with HCPLive, Deepak Sambhara, MD, a partner and medical director of research at Eye Clinic of Wisconsin, indicated the ‘magic’ of the post-hoc analysis is when examining the quartiles for those with the most swollen retinas and their rates of fluid re-accumulation across aflibercept treatment arms.

“What that tells me as a treating retina specialist is that folks with more swollen retinas at baseline have more circulating VEGF that needs to be suppressed,” Sambhara told HCPLive. “That also reiterates the importance of having a higher-dosed VEGF agent on the market that can contribute to that initial VEGF suppression, particularly in the more difficult-to-treat DME patient population.”

PHOTON, a randomized, double-masked, 96-week, non-inferiority trial, evaluated patients with DME who received aflibercept 8 mg every 12 (Q12W) or 16 weeks (Q16W) after 3 initial monthly doses, or aflibercept 2 mg every 8 weeks (Q8W) after 5 monthly doses.

This posthoc analysis measured the effect of each treatment group on BCVA and CRT through Week 48, according to baseline CRT quartiles: Q1 ≤360 µm; Q2, >360-≤430 µm; Q3, >430 to ≤528 µm; Q4, >528 µm. Upon analysis, Sambhara and colleagues identified a general trend of decreasing mean BCVA and increasing mean CRT across the baseline quartiles.

At Week 48, the team observed a generally comparable mean BCVA across treatment groups from Q1 to Q3. However, in Q4, those treated with Q16W aflibercept 8 mg had lower mean BCVA at baseline and Week 48 versus aflibercept 8 mg 12W and aflibercept 2 mg Q8W.

Meanwhile, the mean CRT at Week 48 was comparable across treatment groups in Q1 to Q3, with slightly higher mean CRT values in Q4. After examination of Q4, the mean increase in CRT 8 weeks after the final initial monthly dose was +4 µm in aflibercept 8 mg Q12W, +6 µm in aflibercept 8 mg Q16W, and +56 µm in aflibercept 2 mg Q8W.

“The fact is, we can use this data set and this post hoc analysis to help stratify the patients that might be able to be fast-tracked into longer treatment intervals, versus the folks who might require a little bit more TLC, the folks who will need to be treated more often,” Sambhara told HCPLive.

Disclosures: Sambhara reports relevant consultant fees from Apellis Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and others.


Sambhara D. Impact of baseline central retinal thickness (CRT) on vision among patients with diabetic macular edema (DME): post hoc analysis of the phase 2/3 PHOTON trial. Poster presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.