Dolly Chang, MD, PhD: Importance of Early Drying on Outcomes in DME

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Dolly Chang, MD, PhD, describes results from an exploratory analysis on the long-term impact of rapid fluid reduction on outcomes in DME.

Greater reductions in intraretinal fluid (IRF) volumes within 1 month were linked to improvements in one-year anatomical and visual outcomes among patients with diabetic macular edema (DME), according to a new exploratory analysis presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting.

Eyes with DME from the phase 3 YOSEMITE and RHINE trials were assessed at baseline, 1-month, and 1 year by spectral domain optical coherence tomography (SD-OCT), and analyzed via a deep learning-based segmentation model. Comparisons were made by fluid volume, thickness, and best-corrected visual acuity (BCVA) change from baseline to determine treatment response.

In an interview with HCPLive, investigator Dolly Chang, MD, PhD, Genentech Research and Early Development, noted that the patients with ≥50% volume reduction in IRF exhibited better drying at the one-year mark, with greater reductions in total retinal thickness, inner retinal thickness, and retinal fluid.

“I think what we’re really excited to learn from this paper is that the early drying and better response to the first dose of therapy seems to be strongly associated with better vision and anatomical outcomes at one year,” Chang told HCPLive.

Eyes from 887 patients with DME, treated with faricimab or aflibercept, in YOSEMITE and RHINE were identified for use in the exploratory analysis, based on the availability of quantitative metrics. The measurements included IRF, subretinal fluid (SRF), total retinal fluid volumes, outer nuclear layer (ONL), and inner retinal thickness, averaged over the entire 3-mm diameter ETDRS subfield.

Patients were separated into groups based on the reduction in IRF volume (<20%, 20-50%, >50%) from baseline with measures at week 4. The deep-learning model was trained on an independent dataset of B-scans from the phase 2 BOULEVARD trial.

At the 4-week mark, IRF volume was reduced by <20% in 242 patients, 20 to 50% in 248 patients, and >50% in 397 patients. At the 1-year mark, IRF volume decreased by 270 nL, 378 nL, and 410 nL, respectively.

Changes in IRF volume (P <.001), total retinal thickness (P <.001), ONL (P = .0026), and inner retinal thickness (P <.001) were deemed nominally significant between groups at 1 year when adjusting for baseline IRF. The analysis demonstrated no difference in SRF volume reduction from baseline between groups at the 1-year mark.

Meanwhile, patients with >50% IRF volume reduction at week 4 experienced nominally higher letter gains at 1-year, compared with those with less reduction (>50%: 12.2 letters versus 20 to 50%: 10.6 letters; P = .047 and >50%: 12.2 letters versus <20%: 8.2 letters; P <.001), after adjusting for baseline IRF.

Chang indicated the analysis is limited by the exploratory design, as patients in a clinic may exhibit differences from trial patients, based on background disease and the timing of retinal fluid.

“I think that this is exciting to give us some insight that early drying seems to be important,” Chang told HCPLive. “I do think we need to recognize the individual differences in response and their background disease as well.”

Disclosures: Dolly Chang, MD, PhD is employed by Genentech, Inc.


Wang Y, Hibar D, Maunz A, Lu H, Albrecht T, Gibson K, Willis JR, Chang D, Litts KM. Impact of Early Intraretinal Fluid Reduction on One-Year Outcomes in Diabetic Macular Edema. Paper presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.