Retinal Vein Occlusion 2010An Evidence-Based ApproachCorticosteroids, Implants, and Anti VEGF Therapies Allen C. Ho, MD Professor of Ophthalmology Wills Eye Institute Mid Atlantic Retina firstname.lastname@example.org
Disclosures • Research Grant Funding: Alcon Laboratories, Allergan, Genentech, NEI/NIH, NeoVista, Ophthotech, Oraya, PRN, QLT, Regeneron, Second Sight • Consultant / Scientific Advisory Boards: Alcon, Allergan, Centocor / Johnson and Johnson, Genentech, NeoVista, Merck, Ophthotech, Oraya, PRN, QLT, Regeneron
Retinal Vein Occlusion • Retinal vein occlusion is the second most common cause of visual loss due to retinal vascular disease1-3 • Two major types: • Branch retinal vein occlusion (BRVO) • Central retinal vein occlusion (CRVO) • BRVO is the most common3 • Five-year incidence of 0.6% (21/3558) for BRVO and 0.2% (7/3593) for CRVO3 • Persistent macular edema causes VA loss 1. Yau et al. Intern Med J. 2008; 2. RCO RVO guidelines. 2009; 3. Klein et al. Trans Am Ophthalmol Soc. 2000.
Clinical Trials and Venous Occlusive Diseases Laser studies 1980s Branch Vein Occlusion Study (BVOS) 1990s Central Vein Occlusion Study (CVOS) 2009 Steroid studies SCORE Study Ozurdex Trials 2010 Anti-VEGF Ranibizumab studies BRAVO and CRUISE
Primary Results: The Standard Care versus COrticosteroid for REtinal Vein Occlusion Study (The SCORE Study) SCORE Study Research Group Sponsored by the National Eye Institute, National Institutes of Health, U.S. Department of Health and Human Services (Funded by NEI 2003)
SCORE BRVOMean Change BCVA BRVO Trial M12 M4 M8 M16 M20 M24 M28 M32 M36 • After month 12 and through month 36, mean VA improvement was greatest in the SC group.
SCORE BRVO Conclusion • The SCORE-BRVO trial results support grid laser as the SC treatment for macular edema secondary to BRVO because: • Similar efficacy in all 3 treatment arms up to month 12 • Improved efficacy for laser beyond month 12 • Superior safety profile of SC over 1-mg and 4-mg TA
SCORE CRVO BCVA at Month 12 CRVO Trial *Odds ratio adjusted for baseline visual acuity.
SCORE CRVO % With VA Gain of 15 letters or More CRVO Trial M12
Elevated IOP/Glaucoma CRVO Trial *P=.02 for Obs vs 1 mg; P<.0001 for Obs vs 4 mg; P=.02 for 1 mg vs 4 mg. †Procedure for angle closure glaucoma. ‡Procedures to treat neovascular glaucoma.
Both triamcinolone groups were superior to the observation group for VA at 12 months Visual benefit as early as 4 months Visual benefit continued to 24 months The 1-mg dose has a safety profile superior to that of the 4-mg dose and similar to observation SCORE CRVO Conclusion CRVO Trial
OZURDEX™ (dexamethasone intravitreal implant) • OZURDEX™ is preloaded into a sterile, single-use, specially designed applicator to facilitate injection of implant directly into the vitreous • Injectable, biodegradable intravitreal implant contains 0.7 mg (700 μg) dexamethasone in the NOVADUR™ solid polymer drug delivery system (preservative-free). • Poly (D,L-lactide-co-glycolide) PLGA biodegradable polymer matrix, which slowly degrades to lactic acid and glycolic acid as dexamethasone is gradually released. Applicator and Extruded Implant (Not Shown Actual Size)
Ozurdex Mean Change BCVA BRVO Subanalysis P<.001 OZURDEX™ (n=291) Sham (n=279) P<.001 P<.001 P=.008 Study Day P values are for OZURDEX™ vs sham.
Ozurdex Mean Change BCVA CRVO Subanalysis OZURDEX™ (n=136) P<.001 Sham (n=147) P<.001 P=.005 P=.305* Study Day P values are for OZURDEX™ vs sham. *NS at day 180.
100 OZURDEX™ (n=427) 90 Sham (n=426) 80 70 60 50 40 30 20 10 0 0 20 40 60 80 100 120 140 160 180 Ozurdex Primary Outcome = Time to Achieve ≥15-Letter Improvement From Baseline BCVA Log–Rank Test P–value OZURDEX™ vs Sham: P<.001 No. at Risk OZURDEX™ 381 309 264 149Sham 405 374 345 168 Cumulative Response Rate (%) Days from the First Dose
Ozurdex Key Adverse Events *Intravitreal injections have been associated with endophthalmitis. Increased IOP with dexamethasone intravitreal implant (OZURDEX™) 0.7 mg peaked at day 60 and returned to baseline levels by day 180.
Ozurdex Trials Conclusions DEX groups’ time to gain 15 letters was significantly shorter than sham eyes through day 90 Mean change in BCVA was statistically: Better for DEX groups for BRVO through day 180 Better for DEX groups for CRVO through day 90 Persistence of efficacy in 21% BRVO; 17% CRVO at month 12 required only 1 Rx
Anti-VEGF Trials Ranibizumab (Lucentis) BRAVO and CRUISE Afilbercept (VEGF-Trap eye, Regeneron) Galileo and Copernicus Results pending J Lim
BRAVO Study Six-month phase 3 study with 6 months of follow-up; 93 sites 20/40 to 20/400 (mean 20/ 80) CST 250 microns (mean 488 µ sham, 552 µ ranibizumab) Foveal center ME within 12 months BRVO or HRVO Campochiaro PA et al. Ophthalmology. 2010;117:1102-1112. J Lim.
Mean Change from Baseline BCVA over Time to Month 12 Sham/0.5 mg (n=132) 0.3 mg Ranibizumab (n=134) 0.5 mg Ranibizumab (n=131) +18.3* 20 +18.3* 18 +16.4* 16 +16.6* 14 +12.1 12 Mean Change from Baseline BCVA (ETDRS Letters) 10 8 +7.3 6 4 2 0 0 7 2 4 6 8 10 12 Day 0–Month 5 Monthly Treatment Months 6–11 PRN Treatment Month *P<0.0001 vs. sham. Earliest statistically significant group difference (P<0.0001 vs. sham) was at Day 7. Vertical bars are ±1 standard error of the mean. The last-observation-carried-forward method was used to impute missing data. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.
CRUISE Study Six-month phase 3 study, with 6 months of follow-up; 95 sites; 392 patients 20/40 to 20/400 (mean 20/100) CST 250 microns (mean 687 µ sham, 689 µ ranibizumab) Foveal center ME within 12 months CRVO Brown DM et al. Ophthalmology. 2010;117:1124-1133.
Mean Change from Baseline BCVA over Time to Month 12 Sham/0.5 mg (n=130) 0.3 mg Ranibizumab (n=132) 0.5 mg Ranibizumab (n=130) 18 +14.9* 16 +13.9 14 +13.9 12 +12.7* 10 Mean Change from Baseline BCVA (ETDRS Letters) 8 +7.3 6 4 +0.8 2 0 -2 0 7 2 4 6 8 10 12 Day 0–Month 5 Monthly Treatment Months 6–11 PRN Treatment Month *p<0.0001 vs. sham. Earliest statistically significant group difference (p<0.0001 vs. sham) was at Day 7. Vertical bars are ±1 standard error of the mean. The last-observation-carried-forward method was used to impute missing data. BCVA=best-corrected visual acuity, ETDRS=Early Treatment Diabetic Retinopathy Study.
Key Study Eye Adverse Events Through Month 6 *Reported as serious. †One vitreous hemorrhage was reported as serious.
BRVO Summary BRVO: SCORE: Laser better than IVTA OZURDEX: Dexamethasone better than sham (no laser arm) BRAVO: Ranibizumab monthly for 6 months better than observation/laser in BRAVO. Improved VA: 61% vs 29% eyes gained 15 or more letters
CRVO Summary CRVO treatment options Steroids beneficial in phase 3 studies SCORE Study: IVTA vs observation OZURDEX Trials: dexamethasone vs sham Anti-VEGFs CRUISE: Ranibizumab monthly for 6 months better than observation. Improved VA: 48% vs 17% eyes gained 15 or more letters VEGF Trap: Galileo and Copernicus pending
Retinal Vein Occlusion 2010 • Allen C. Ho, MD • Wills Eye Institute Philadelphia • email@example.com