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Fuchs endothelial corneal dystrophy (FECD) is the most common corneal dystrophy and frequently results in vision loss. Hallmarks of the disease include loss of corneal endothelial cells and formation of excrescences of Descemet's membrane. Later stages involve all layers of the cornea. Impairment of endothelial barrier and pump function and cell death from oxidative and unfolded protein stress contribute to disease progression. The genetic basis of FECD includes numerous genes and chromosomal loci, although alterations in the transcription factor 4 gene are associated with the majority of cases. Definitive treatment of FECD is corneal transplantation. In this paper, we highlight advances that have been made in understanding FECD's clinical features, pathophysiology, and genetics. We also discuss recent advances in endothelial keratoplasty and potential future treatments.

Purpose: To evaluate visual outcomes, endothelial cell density and complications following Descemet′s membrane endothelial keratoplasty (DMEK). Methods: This study included 40 consecutive eyes that underwent DMEK for various pathologies involving the corneal endothelium. Best corrected visual acuity (BCVA) and endothelial cell density (ECD) were measured and compared before and 6 months after surgery. Results: Out of 40 eyes, 34 eyes (85%) had BCVA ranging from 0.5 to 0.7 LogMAR 6 months postoperatively. Mean donor ECD was 2367.96 ± 47.87 (range, 2314.0-2472.0) cells/mm 2 preoperatively, which was reduced to 1798.42 ± 45.79 (range, 1736.0-1902.0) cells/mm 2 6 months after DMEK surgery, indicating a mean reduction of 569.54 cells/mm 2 (24%) in ECD. Conclusion: DMEK is an emerging and a more advanced alternative to penetrating keratoplasty (PKP) and Descemet′s stripping endothelial keratoplasty (DSEK) for corneal pathologies involving the corneal endothelium. Compared to PK and DSEK, however, DMEK has a longer learning curve, and its safety and efficacy need to be confirmed through more experience on a large volume of cases.

To present the changing indications and surgical techniques for keratoplasty during a 16-year period (2003-2018) at a tertiary referral hospital in Japan. Consecutive keratoplasty cases at Kanazawa University Hospital from January 2003 to December 2018 were retrospectively reviewed. Keratoplasty procedures included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), anterior lamellar keratoplasty (ALK), Descemet's stripping automated endothelial keratoplasty (DSAEK), and Descemet's membrane endothelial keratoplasty (DMEK). Annual numbers and types of keratoplasty as well as underlying diseases for PK and total keratoplasty procedures were recorded, and annual trends were statistically analyzed using Cochran-Armitage test for trend. A total of 801 keratoplasty procedures (PK, 319 cases; DALK, 57 cases; ALK, 9 cases; DSAEK, 371 cases; and DMEK 45 cases; mean age, 66.9±16.3 years) were performed for 595 patients (302 males [329 eyes, 419 cases], 293 females [345 eyes, 382 cases]) during the 16-year period. The proportion of PK procedures decreased significantly in the beginning and showed a slightly increasing trend after a plateau around 2015. DSAEK was increasing after 2006 and reached a plateau around 2012. Among 10 underlying diseases for total keratoplasty, corneal opacity and dermoid were decreasing linearly. Failed PK and failed DSAEK were increasing linearly in the beginning and reached a plateau followed by a decreasing trend. In terms of the underlying disease for PK, bullous keratopathy was decreasing in the beginning and reached a plateau around 2015. A total of 19 PK procedures were performed on cases with recalcitrant bullous kerstopathy (BK) after 2010. The distribution of keratoplasty procedures and underlying diseases changed significantly over 16 years at a tertiary referral hospital in Japan. PK procedure was significantly decreased and DSAEK procedure was significantly increased. PK for BK decreased significantly; however, PK remains a viable option for other recalcitrant corneal diseases.

To assess clinical outcomes after Descemet's Membrane Endothelial Keratoplasty (DMEK) with mydriatic eye drops without peripheral iridotomy (PI-less). We performed a retrospective, observational clinical study to determine the postoperative intraocular pressure (IOP) changes and graft viability in a cohort of patients with Fuchs' endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). Included in this study were 41 PI-less DMEK patients with 44 eyes (median age: 77 years; range: 53-88 years). Patients received either PI-less DMEK (group-1) or PI-less triple DMEK (group-2). The mean follow-up duration was 16 months. Eyes after standard DMEK or triple DMEK served as controls (n = 20). Included in the study were patients admitted to the hospital (securing IOP control), patients in which the tamponading agent was air or gas (SF6) and only patients with physiological air resorption, ie without routine, postoperative air/gas release (90% air/gas fill of the anterior chamber at end of surgery). Phakic eyes were not included. Postoperatively, mydriatic eye drops were administered for three days 4x/d (phenylephrine 25 mg/mL, tropicamide 5 mg/mL). The best-corrected visual acuity (BCVA), endothelial cell density (ECD), and IOP were assessed. Intra- and postoperative complications and management were recorded. BCVA improved significantly in both groups (group-1:0.90 ± 0.57 to 0.20 ± 0.23logMAR (p = 0.000); group-2:0.47 ± 0.23 to 0.17 ± 0.42logMAR (p = 0.0067). ECD decreased significantly: Group-1 2428±225 cells/mm to 1810±236 cells/mm (p = 0.005); group-2 2447 ± 178 cells/mm to 1866 ± 229 cells/mm (p = 0.012). After postoperative day-1 IOP decreased significantly: Group-1 p = 0.004 (10.0 ± 2.8 mmHg) and p = 0.002 (11.3 ± 3.1 mmHg); group-2 p = 0.002 (10.7 ± 3.6 mmHg) and p = 0.002 (11.4 ± 2.2 mmHg); for postoperative days 2 and 3, respectively. Postoperative adverse events included pupillary block necessitating emergency air release. Intergroup analysis did not show a significant difference in ECD, IOP (after postoperative day-1) and logMAR (after 6 months). Patients may benefit from the promising results of the study regarding postoperative IOP developments and graft viability after DMEK using mydriatic eye drops (phenylephrine 25 mg/mL, tropicamide 5 mg/mL). PI-less triple DMEK in particular might improve accessibility, reduce surgical complexity, or lower costs, making it attractive in resource-limited settings. Close postoperative IOP monitoring is advised in PI-less DMEKs.

Purpose: To compare the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) combined with phacoemulsification versus DMEK following phacoemulsification. Methods: In this interventional retrospective comparative nonrandomized case series study, patients with Fuchs endothelial corneal dystrophy (FECD) with either cataract or previous cataract surgery with intraocular lens (IOL) implantation were assigned to one of the two groups according to lens status. Group 1 included patients who had cataract and FECD and would undergo triple procedure (phacoemulsification with IOL implantation and DMEK), whereas Group 2 included patients who had FECD and had phacoemulsification with IOL implantation earlier and would undergo DMEK only as a sequential procedure. Results: Postoperative best corrected visual acuity (BCVA) in both groups at 1 week, 1 month, 3 months, and 6 months revealed a statistically nonsignificant difference between the two groups with mean logMAR BCVA at 6 months of 0.07 ± 0.18 and 0.07 ± 0.19 in Group 1 and Group 2, respectively (P > 0.05). The drop in endothelial cell density by the end of the 6th postoperative month was by 39.44% ±7.92 and 38.73% ±8.10 in the triple-procedure group and DMEK only group, respectively (P = 0.005). Total postoperative complications rate and the rebubbling rate were statistically similar between both groups with 13.5% and 12.5% rebubbling rate in Group 1 and Group 2, respectively (P > 0.05). Conclusion: Visual outcomes, endothelial cell loss, and rebubbling rate are comparable when DMEK is combined with phacoemulsification or when it is performed as staged procedure, without statistically significant difference in the outcomes.

Purpose: Various injectors are commercially available for Descemet membrane endothelial keratoplasty (DMEK) but not all injectors have been studied for endothelial damage of grafts. The aim of the study was to compare endothelial damage in pre-stripped DMEK tissue from three clinically used injector devices: the modified Jones tube, the STAAR intraocular (IOL) injector, and the Geuder glass cannula in a laboratory setting. Methods: Twenty-four human donor corneas were used for this study, eight for each study arm. Each endothelial graft was pre-stripped, trephined to 8.0 mm diameter, then loaded into either the modified Jones tube, the STAAR IOL injector, or the Geuder glass cannula by an eye bank technician who had no prior experience with any of the injectors. Grafts were then ejected, stained with Calcein acetoxymethyl (AM), and quantitatively analyzed using FIJI image software. The primary outcome was the percent of endothelial damage from injector loading and injection. Donor demographics were analyzed using Fisher's exact test. The percentage of endothelial cell loss was compared across groups using the Kruskal-Wallis test. Results: The mean percent of endothelial damage from after injection of the graft was 37.8% (±SD 12.2%) for the modified Jones tube, 37.0% (±SD 13.9%) for the STAAR IOL injector, and 23.5% (±SD 5.1%) for the Geuder cannula (P = 0.008). Conclusion: DMEK injectors contribute to intraoperative endothelial damage of transplanted grafts. The Geuder glass cannula may offer increased ease of use and less endothelial damage compared to the modified Jones tube or STAAR IOL injector for the novice user in early cases.

Purpose: To present the management of upside-down Descemet membrane endothelial keratoplasty (DMEK) following combined phacoemulsification with DMEK (phaco-DMEK) in cases of Fuchs endothelial dystrophy (FED). Methods: This is a comparative interventional case series extracted from a prospective interventional case series (clinical outcome of DMEK combined with phacoemulsification for FED). We report five cases of upside-down DMEK. Two cases of upside-down DMEK were managed with re-orientation and the other two with repeat DMEK. The 5th case underwent an initial re-orientation and then a subsequent repeat graft. Graft re-orientation and repeat surgery were performed 9-20 days after initial phaco-DMEK. All the five cases were followed up over a 6-month period, and the following outcomes were assessed: best corrected visual acuity (BCVA), contrast sensitivity (CS), central corneal thickness, endothelial cell density (ECD), and central macular thickness. Results: At the final 6-month postoperative follow-up, all the five cases achieved good outcomes in terms of BCVA and CS. Overall, the results were comparable to 32 control cases. One case of re-orientation and the case of re-orientation with subsequent repeat DMEK performed slightly less well than control cases in terms of postoperative ECD. Conclusions: Re-orientation of the original DMEK scroll in cases of upside-down DMEK can be a safe and cost-effective alternative to repeat DMEK. If re-orientation does not result in corneal deturgescence, a repeat DMEK may be done subsequently.

Descemet membrane endothelial keratoplasty (DMEK) is the current gold standard surgical procedure to treat Fuchs endothelial keratoplasty. Cataract removal and intraocular lens (IOL) implantation can be safely combined with this corneal procedure. This paper presents a case series in which a toric intraocular lens (IOL) was used in combined DMEK and cataract surgery to correct corneal astigmatism. Four eyes that had a toric IOL implanted in combined cataract and DMEK surgery were included. There was a reduction in manifest refractive cylinder and improvement in uncorrected and best-corrected vision in all cases. Surgeons may consider the use of toric IOLs in selected cases of combined DMEK and cataract surgery for Fuchs endothelial dystrophy.

Background To evaluate the clinical outcomes and features of Descemet’s membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). Methods In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery about four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. Results This study included 14 eyes of 14 patients (PEX: n  = 6, FECD: n  = 8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 at the preoperative point to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2704 ± 225 cells/mm 2 at the preoperative point and decreased to 1691 ± 498 cells/mm 2 at 1 month, 1425 ± 366 cells/mm 2 at 3 months, and 1281 ± 340 cells/mm 2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT ( p  = 0.821); BSCVA ( p  = 0.001) and the reduction rate of ECD ( p  = 0.010) were relatively worse. Conclusions DMEK is effective for the treatment of endothelial dysfunction due to PEX.

Purpose: To report a modified surgical technique called the “donor tissue holding technique for Descemet’s membrane endothelial keratoplasty (DMEK)” using a newly developed 25-gauge graft manipulator. Methods: Six consecutive patients exhibiting endothelial dysfunction were enrolled and treated by DMEK. In brief, after insertion of a DMEK donor into the anterior chamber, the edge of the roll was grasped using a graft manipulator and this grasp was maintained throughout the centering and opening of the roll (holding technique). The following parameters were evaluated in comparison to the previous 10 consecutive DMEK cases in which the no touch technique was used: time of graft unfolding, incidence of intra-/postoperative complications, and best spectacle-corrected visual acuity (BCVA) and endothelial cell density (ECD) 6 months after the procedure. Results: In both technique groups, neither intra- nor postoperative complications were noted in any case. No differences were observed between the two groups in postoperative BCVA (p = 0.88). Also, no differences were observed between the two groups in postoperative ECD (holding technique group: 2,108.3 cells/mm 2 , no touch technique group: 1,491.7 cells/mm 2 ) (p = 0.08) Most notably, the time of graft unfolding prior to filling with air was significantly reduced in the holding technique group (305.5 s) compared to that of the no touch technique group (1,310.0 s; p = 0.01). Conclusions: This donor tissue holding technique enabled rapid and safe DMEK in a reproducible manner, even in Asian eyes with shallow anterior chambers with high vitreous pressure.