Factors affecting the success rate of pre-loaded DMEK with endothelium-inwards technique: a multi-centre clinical study

Purpose: To evaluate factors affecting the outcomes of pre-loaded DMEK (pl-DMEK) with endothelium-inwards. Design: Retrospective clinical case series and a comparative tissue preparation study PARTICIPANTS: Fifty-five donor tissues for ex vivo study and 147 eyes of 147 patients indicated with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy with or without cataract. Intervention: Standardized DMEK peeling was performed with 9.5 mm diameter followed by second trephination for loading the graft (8.0-9.5 mm diameter). The tissues were manually pre-loaded with endothelium inwards and preserved for 4 days or shipped for transplantation. Live/dead assay and immunostaining was performed on ex vivo tissues. For the clinical study, the tissues were delivered using bi-manual pull-through technique followed by air tamponade at all the centres. Main outcome measures: Tissue characteristics, donor and recipient factors, re-bubbling rate, endothelial cell loss (ECL) and CDVA at 3, 6 and 12 months. Result: At day 4, significant cell loss (p=0.04) was observed in pl-DMEK with loss of biomarker expression seen in pre-stripped and pl-DMEK tissues. Re-bubbling was observed in 40.24% cases. Average ECL at 3, 6 and 12 months was 45.87%, 40.98% and 47.54% respectively. CDVA improved significantly at 3 months post-op (0.23 ± 0.37 logMAR) (p<0.01) compared to the baseline (0.79 ± 0.61 logMAR). A significant association (p<0.05) between graft diameter, preservation time, recipient gender, gender mismatch and recipient age to re-bubbling rate was observed. Conclusion: Graft loading to delivery time of pl-DMEK tissues in endothelium-inwards fashion must be limited to 4 days after processing. Re-bubbling rate and overall surgical outcomes following pre-loaded DMEK can be multi-factorial and centre specific.