Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

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Not AvailableKMR-3R is a stable restorer line with medium-bold grain type and is the male parent of the popular public-bred Indian rice hybrid, KRH2. As both KMR-3R and KRH2 are highly susceptible to bacterial blight (BB) and possess undesirable bold-grain type, we crossed KMR-3R with a high-yielding, BB resistant, fine-grain-type variety, Improved Samba Mahsuri, possessing the major BB resistant gene, Xa21. The F1s were backcrossed to KMR-3R, and the BC1F1 plants were subjected to marker-assisted selection (MAS) for Xa21 and two major fertility restorer genes, Rf3 and Rf4. Triple positive BC1F1 plants were selfed and their progeny were subjected to MAS for Xa21 coupled with phenotype-based visual selection for agromorphological and grainquality traits. At BC1F5 generation, three backcross derived lines (BK9, BK49 and BK61) possessing higher yield than KMR-3R, tall plant stature along with fine-grain type were identified and crossed with IR598025A, the female parent of KRH2. The hybrids were completely fertile, possessed long-slender grain type, exhibited resistance to BB and displayed a yield advantage of 24% over KRH2 under BB infectionIndian Council of Agricultural Research (ICAR) and Department of Biotechnology (DBT