Time-in-Range Analysis of Responses after Intravitreal Dexamethasone Therapy in Eyes with Diabetic Macular Edema.

PURPOSE

Time in range (TIR) is a novel end point that assesses the time during which an outcome remains within a predetermined range. Because the range includes normal parameters, it is indicative of clinically meaningful benefit. The MEAD trial comprised two 3-year randomized, multicenter, sham-controlled, phase III clinical studies that evaluated the efficacy and safety of dexamethasone intravitreal implant (DEX-I) in patients with diabetic macular edema. Dexamethasone intravitreal implant significantly improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT) compared with sham treatment. We present a post hoc analysis of the MEAD trial to investigate TIR benefit across various thresholds of BCVA and CRT with DEX-I versus sham.

DESIGN

Post hoc analysis of results from the randomized, multicenter, sham-controlled, phase III MEAD trial (NCT00168337 and NCT00168389).

PARTICIPANTS

Adults with type 1 or 2 diabetes mellitus and fovea-involved macular edema associated with diabetic retinopathy.

INTERVENTION

Intravitreal injection of DEX-I 0.7 mg or sham procedure.

MAIN OUTCOME MEASURES

Time in range during year 1 was evaluated using BCVA thresholds of ≥69, ≥51, ≥59, and ≥64 letters, and CRT thresholds of <300, <353, <446, and <551 μm (the latter cutoffs being quartile [Q] 1, Q2, and Q3 of pooled baseline BCVA and CRT, respectively).

RESULTS

Dexamethasone intravitreal implant 0.7 mg was associated with a statistically significant longer TIR versus sham at the BCVA ≥69-letter threshold (15.0 vs. 9.1 weeks, respectively; 0.001) and the CRT <300 μm threshold (18.5 vs. 8.3 weeks, respectively; 0.001). Dexamethasone intravitreal implant was also associated with longer TIR versus sham at thresholds of BCVA ≥59 (greater than or equal to Q2) and ≥64 letters (greater than or equal to Q3) and CRT <353 μm (less than Q1), <446 μm (less than Q2), and <551 μm (less than Q3) (all 0.001).

CONCLUSIONS

Patients receiving intravitreal DEX-I 0.7 mg had a longer time with BCVA above the driving threshold and below the normal limit of CRT during year 1 of the MEAD trial versus those who received sham. These results suggest that patients treated with dexamethasone experience a longer time with clinically meaningful outcomes than with sham, such as being able to drive or regaining normal structural retinal features.

FINANCIAL DISCLOSURES

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.