Central Retinal Vein Occlusion Hemi-Central Vein Occlusion Current Management of Retinal Vein Occlusion Robert A. Mittra, MD VRS Course 2015 Branch Retinal Vein Occlusion Ischemic vs. non-ischemic BRVO BRVO 1
Systemic risk factors Newman-Casey Ophthalmol 2014 Survey of Medicare database Hypertension Diabetes Natural History Decroos AJO 2011 has discussed the difficulty of using randomized trials for natural history Control groups were small or had different entrance criteria or lumped together different groups of diseases Hayreh JAMAOpthalmol 2014 BRVO Divided into major and macular Resolution of edema in 18-21 months Overall outcome is good Median final VA 20/60 for both types Natural History Hayreh Ophthalmol 2011 Non-ischemic is 20/100 in 83% Hayreh Retina 2012 HRVO Improves 50% of the time without therapy Unmet Need in Retinal Vein Occlusion 2 nd leading cause of blindness for patients with retinal vascular disease RVO Incidence 180,000 eyes/yr U.S. 80% BRVO 20% 70% Non- Ischemic 30% Ischemic DEMOGRAPHICS Mean age at onset: 65 yrs Male:Female ratio: 1.2:1 Risk Factors: Open-angle glaucoma, HTN, DM, and arteriosclerosis Outcome predictors: VA at diagnosis and age Long-term VA Outcomes VA @ 3 Yrs BRVO 1 2 > 20/40 34% 12% 20/50-20/200 43% 62% < 20/200 23% 26% 1 BVOS: AJO 98: 271-282, 1984 2 CVOS: Ophthalmology 102: 1425-33, 1995 2009, Genentech / Proprietary information Please do not copy, distribute or use without prior written consent. Treatment options Observation Laser Focal for macular edema PRP for ischemia and NVI Anti-VEGF therapy Bevicizumab (Avastin) Ranibizumab (Lucentis) Aflibercept (Eylea) Steroid Intravitreal triamcinolone (Triesence) Dexamethasone implant (Ozurdex) Observation May still be an option for mild BVO and without significant visual loss from macular edema Extramacular BVO almost universally is observed Ischemic BRVO without leakage on FA may improve without therapy 2
30% Spontaneous Recovery BRVO 3 Month Observation 70% Disease Progression 3 Macular Grid Laser BRVO: Laser v. Observation 1 Laser Observation > 2 line VA gain @ 1 Yr* ~20% ~7% Mean VA @ 1 Yr n/a n/a Observation Only <25% Guarded d >75% Disease Recovery Progression : Observation 2 Observation > 3 line VA gain @ 1 Yr* 6% Mean VA @ 1 Yr - 3 letters Laser BVOS study showed that macular laser is better than observation Tan AJO 2014 showed that intravitreal Lucentis gives superior visual results when compared to Laser Campochiaro Ophthalmol 2014 showed intravitreal Eylea better than grid laser at 6 months (VIBRANT) Shah et al feel that focal/grid laser may still be useful in cases of BRVO Pichi Ophthalmol 2014 showed that Ozurdex and grid laser are synergistic for improvement in vision and decreasing frequency of injections Farese Eur J Ophthalmol 2014 showed grid laser with Avastin effective for treatment of BRVO Mean VA @ 3 Yrs + 6.7 letters + 1 letter Mean VA @ 3 Yrs - 3 letters 2009, Genentech 1 BVOS: / Proprietary AJO 98: information 271-282, 1984 Please 2 CVOS: do not copy, Ophthalmology distribute or 102: use without 1425-33, prior 1995 3 Arch Ophthalmology; 110: 1427-1434, 1992 written consent. Laser CVOS study showed grid laser in not beneficial for treatment of macular edema Shah AJO 2011 feel that there may still be a role for laser for treatment of areas of capillary dropout Area of non-perfusion in often increases over time even with therapy (prn therapy with anti-vegf and dexamethasone implant) Retinal Vein Occlusion Pathophysiology Retinal vein compression and narrowing Turbulent blood flow Thrombus formation Ischemia and hypoxia Increased VEGF production Increased capillary permeability (Branch) BRVO (Central) Christoffersen NL, Larsen M. Ophthalmology. 1999.106:2054. Fegan CD. Eye. 2002.16:98. Noma H, et al. Graefes Arch Clin Exp Ophthalmol. 2006. 244:309. 2009, Genentech / Proprietary information Please do not copy, distribute or use without prior written consent. Leakage and edema Vision Loss Anti-VEGF Therapy Marked effect on macular edema, can be see within 1 hour of treatment (Ma Can J Ophthalmol 2014) Avastin Epstein, Algvere Ophthalmol 2012 Effective for over 2 years if therapy is continued every 6 weeks Greater than 15 letter increase in vision in 60% Lucentis Varma Ophthalmol 2012 BRAVO and CRUISE trials showed significant visual gain with Lucentis monthly for 6 months Campochiaro/Wycoff Ophthalmol 2014 showed that after 7 monthly treatments can go prn with Lucentis (SHORE) Anti-VEGF therapy Eylea Brown AJO 2013 showed monthly dosing for 6 months and then prn to 1 year is effective Korobelnik Ophthalmol 2014 showed similar for 1 year for (GALILEO) Ogura AJO 2014 showed similar results for 1.5 years 3
Steroid Scott Arch Ophthalmol 2012 SCORE BVO showed no difference between laser and IOS at 1 year SCORE showed vision was better at 1 year with IOS, but only a small percentage benefit (27%) Haller Ophthalmol 2011 Ozurdex effective for BRVO and in reducing macular edema and improving vision Shaikh Ophth Surg/Laser 2013 showed Ozurdex as effective in vitrectomized eyes as those without Timing of treatment Thach Ophthalmol 2014 showed early treatment with Lucentis much better for BRVO/ with monthly rx for 6 months, rescue treatment not as good Ogura AJO 2014 showed a similar result with Eylea for, rescue treatment not effective Ideally want to see and initiate treatment on patients within the first 1-2 months after onset Long term Therapy? Kinge AJO 2010 showed long term therapy is required to maintain vision gains in patients treated with Lucentis Heier Ophthalmol 2014 (COPERNICUS) 2 year follow-up of Eylea for showed the visual gains noted at 1 year were lost with less frequent follow up in year 2 Once disease recurs may not do as well,?long term treatment every 2 months Heier/Campochiaro Ophthalmology 2012 (HORIZON) decrease in Follow-up in year 2 resulted in loss of vision for, but not BRVO patients treated with Lucentis Non-perfusion Sadda Ophthalmol 2013 showed Ozurdex treated patients have stabilization of NV and macular edema but non-perfusion increases despite therapy Sophie Ophthalmol 2013 showed prn treatment with Lucentis allows for an increase in retinal non-perfusion and loss of visual gains achieved 4
Campochiaro/Sophie Ophthalmol 2014 (RETAIN) 4 year follow-up of Lucentis for BRVO/ Most BRVO did well long term with resolution of fluid by 2 years Of those still requiring injections, 80% were >20/40 44% of had resolution of edema within 4 years, but the majority still needed injections beyond with a guarded prognosis for vision Data do not apply to those with Va <20/400 or and APD Poor outcomes seen in patients with increased age, HTN and ischemia Hahn AJO 2013 Eylea, Lucentis, Avastin, Ozurdex are all shown to be effective for BRVO/ compared to sham injections Unknown how they are against each other Unknown how they should be used long term More unknown than known Take Home Message What to tell patients? BRVO Prognosis is good for retained or improved vision Will need therapy for at least 2 years May consist of injections of various agents and laser (non-ischemic) Prognosis is guarded for long term vision About a 4/10 chance of improvement Therapy beyond 2 years is likely May consist of injections of various agents and possibly laser 5
Thank You 6