1. DSAEK in Eyes With Severe Pre-operative Visual Acuity Loss. 1. Sightline Ophthalmic Associates, Pittsburgh, PA 2. Devers Eye Institute, Portland, OR 3. Lions Eye Bank of Oregon Vision Research Laboratory, Portland, OR Financial interest statement: Mark A. Terry, MD has a financial interest in the specialized DSAEK instruments used in this study. Funding for this project was supplied by The Lions Eye Bank of Oregon. Paul Phillips, MD 1,2, Mark A. Terry, MD 2,3, Neda Shamie, MD 2, Anand Shah, MD 2, and Daniel Friend 3

2. Introduction Endothelial Keratoplasty (EK) is a technique for the selective replacement of diseased corneal endothelium. Descemet’s Stripping Automated EK (DSAEK) has become the most commonly used technique of EK today for the treatment of endothelial dysfunction. Previous studies have demonstrated the benefit of EK in the form of deep lamellar endothelial keratoplasty (DLEK) for eyes with severe vision loss (VA<20/400) 1,2. To date, no study has evaluated outcomes of the treatment of these eyes with DSAEK. The specific goal of this study was to determine whether acceptable outcomes could be achieved in this severe vision loss group in the form of low complications, dislocations, primary graft failures (PGF), endothelial cell loss and late endothelial failures.

3. Methods Data collection: Eyes with severe pre-operative vision loss (SVL)( /=20/400) (n=538). Patients were evaluated at 1month for: -Intra-operative complications -Post-operative dislocations -Primary graft failure (PGF) Patients were evaluated at 6 months and 12 months for: -Best spectacle visual acuity (BSCVA) -Endothelial cell density (ECD) -Late endothelial failure Data Analysis -These parameters were evaluated for statistical significance by Chi- Square independent sample T tests, using SPSS 12.0.

4. Results SVLControlp-value Comorbidities*65%27%0.000 * Optic neuropathy, retinal pathology, iritis, ICE syndrome, HSV, surface disease Severe Vision Loss Group (BSCVA) Follow up time point Average Improved Vision >/= 20/40 6mo(n=23)20/122(20/20-20/2000)96%(n=22)35%(n=8) 12mo(n=17)20/108(20/25-HM)88%(n=15)35%(n=6) Control Group (BSCVA) Follow up time point Average Improved Vision >/= 20/40 6mo(n=361)20/35 (20/10 -20/400) 82%(n=295)83%(n=300) 12mo(n=257)20/24 (20/10 – 20/2000) 84%(n=215)85%(n=219) Pre-Operative Comorbidities: Study vs. Control Post-Operative Vision

5. Results Severe Vision Loss Group (BSCVA) No Comorbidity With Comorbidity P Value Pre-Operative20/4050(CF)20/3050(CF)0.359 6mo(n=23)20/50(n=5)20/155(n=18)0.007 12mo(n=17)20/39(n=4)20/147(n=13)0.220 VA of SVL eyes: with comorbidities vs. no comorbidities BSCVA was better in the “no comorbidity” group, but only statistically significant at 6mo

6. Results SVLControlp-value *Operative Complication 5%(n=2)1%(n=5)0.031 Dislocation7%(n=3/43)2%(n=11/538)0.042 PGF01n/a * Excessive manipulation or damage of corneal tissue, iris damage, loss of donor tissue, compromise of filtering bleb and other. Complications

7. Results SVLControlp-value Pre-op ECD 27932755 6mo ECD (% Cell Loss) 1640(35%)2004(26.9%)0.013 12mo ECD (% Cell Loss) 1587(36.2%)2005(27.6%)0.019 Late Endothelial Failure (Eyes with at least one year f/u) 5.8%(n=2/36)0.3%(n=1/362)0.000 Endothelial Health

8. Results Figure 1a: Pre-op EK for Bullous Keratopathy from trauma BSCVA: CF Figure 1b: 3yrs post-op EK for Bullous Keratopathy from trauma BSCVA: 20/30 Example Patient

9. Discussion When compared to a time matched control group, vision in the SVL group was more limited. – –This limitation in vision may be due to a higher rate of comorbidities, but may also be limited by inherent chronic stromal changes, as there was not a significant difference in final acuities between eyes with and without comorbidities at one year in the SVL group. While there was not a higher incidence of PGF in SVL group, there were higher rates of dislocation and intra-operative complications. – –We believe that the dislocation (7%) and intra-operative complication (5%) rates in the SVL group are acceptable, however these rates may be higher than the control group due to the more complex nature of surgery in these eyes. Post-operative endothelial cell loss is also higher in the SVL group, with increased rates of late endothelial failure. – –We believe that rates of ECD loss (36.2%) and late endothelial failure (5.8%) are acceptable, but may possibly be higher due to increased intra-operative trauma and significant comorbidities, such as the presence of glaucoma, filtering tubes and trabeculectomies. – –In the future, data from a greater number of eyes with SVL, with long term follow- up, will help to clarify the true difference in outcomes in this population.

10. Discussion Despite a significantly higher rate of comorbid conditions in the severe vision loss (SVL) study group, DSAEK was performed in these eyes with relatively: - Low intra-operative complications - Low dislocation rates - Low primary graft failure rates - Improved vision - Reasonable preservation of endothelium and rates of late endothelial failure