In vivo confocal microscopy findings after Descemet stripping only with and without topical ripasudil supplementation in Fuchs endothelial dystrophy.

OBJECTIVE: To report corneal epithelial and corneal endothelial cell (CEC) changes following Descemet stripping only (DSO) with and without topical ripasudil using in vivo confocal microscopy (IVCM). METHODS: Prospective interventional case series of patients who underwent DSO for Fuchs endothelial dystrophy with or without postoperative topical ripasudil (4%, 6 times per day). Patients underwent IVCM (ConfoScan 3; NIDEK Technologies, Padova, Italy) at baseline, monthly until corneal clearance, and then every 6 months. En face images were obtained of the epithelium, anterior and posterior corneal stroma, and endothelium of the central and superior cornea. The epithelial and endothelial layer images were evaluated qualitatively. RESULTS: IVCM imaging was obtained from 34 patients, 26 (76%) of whom were supplemented with ripasudil and 8 (24%) of whom were not. Two eyes (6%) did not clear and required a keratoplasty. IVCM confirmed epithelial and endothelial cell morphology changes and reestablishment of a CEC mosaic. Hyperreflective nuclei, pleomorphism, multinucleated cells, and pseudoguttae were identified within the descemetorhexis. In patients on ripasudil, epithelial cells demonstrated transition from stratified squamous to spindle cell shape in regions of ripasudil-induced honeycomb edema. Migrating cells adopted an amoeboid shape and cytoplasm elongation when crossing to central stroma. Transient epithelial cell morphology changes and endothelial cell amoeboid shape changes appear to be uniquely associated with ripasudil. Rarely, figures were noted in both ripasudil-treated and non-ripasudil-treated corneas that resembled mitotic bodies. CONCLUSIONS: CECs display a range of adaptive mechanisms during healing to re-form the endothelial mosaic following DSO. Ripasudil administration appears to induce unique epithelial and endothelial cell changes.

Medium-Term Failure of Descemet's Stripping Only and Fuchs' Dystrophy With Pancorneal Guttae.

PURPOSE: The purpose of this study was to report the medium-term outcome of our index case of Descemet stripping only (DSO) in the clinical setting of Fuchs endothelial corneal dystrophy with pancorneal guttae. METHODS: This was a retrospective case report. RESULTS: A 44-year-old woman with bilateral Fuchs endothelial corneal dystrophy was referred for consideration of DSO. At initial slit-lamp examination, widespread guttae were observed with no clear zone visible. Confocal microscopic examination also failed to isolate a population of undisturbed endothelial cells. DSO with supplemental ripasudil was performed with corneal clearance achieved at 2.5 months. A stable result was obtained for 18 months with a subsequent slow decline in vision and return of diurnal fluctuation. At 3.5 years after DSO, DMEK was performed with resolution of symptoms. CONCLUSIONS: Medium-term failure in this clinical setting is further evidence that DSO is likely best offered to patients with central guttae but a clear corneal periphery, indicative of a healthy cell reservoir.

Descemet Stripping Only Supplemented With Topical Ripasudil for Fuchs Endothelial Dystrophy 12-Month Outcomes of the Sydney Eye Hospital Study.

PURPOSE: To report early safety and efficacy of Descemet stripping only (DSO) supplemented with ripasudil. METHODS: A pre-post clinical trial with a historical control group for time to heal and cell count parameters. The study received ethics approval and was conducted with oversight of a data safety monitoring board. All enrolled patients had a superior endothelial cell count of >1000 cells/mm2 and were symptomatic from the presence of central guttata degrading vision and/or producing glare. DSO was carried out with a peeling technique and not combined with any other intervention. Ripasudil 0.4% was applied topically from day 1 postoperatively at a dose of 6 times/d until corneal clearance. Cases with relapse of edema were permitted to restart on ripasudil at a reduced dose of 2 drops/d for a further 2 weeks. Stopping rules with progression to a corneal graft were established. Baseline ocular and systemic investigations were carried out and repeated at varying intervals to monitor for local and systemic adverse events. RESULTS: Twenty-three eyes of 23 patients met the inclusion criteria and underwent DSO. Twenty-two of 23 eyes achieved corneal clearance at a mean time of 4.1 weeks. In all patients achieving clearance, improvement in vision was recorded. Improvement in mean uncorrected visual acuity was 0.20 Logarithm of the minimum angle of resolution (LogMar), and improvement in mean best spectacle corrected visual acuity was 0.156 LogMar. One patient failed to clear and underwent Descemet membrane endothelial keratoplasty at week 12. Twenty-one of 22 patients achieving corneal clearance expressed satisfaction with the procedure. The commonest systemic side effect of topical ripasudil was gastrointestinal upset (24%), and the commonest local side effect was ocular irritation (43%). No patient experienced a serious adverse event in the course of the trial. Thirty-nine percent of patients experienced a relapse of edema on ceasing ripasudil, with clearance again on recommencing. CONCLUSIONS: This trial of DSO supplemented with ripasudil included local and systemic safety analysis. We judge that this treatment option is emerging as a reliable intervention for select patients with Fuchs' Endothelial Corneal Dystrophy (FECD) with an acceptable safety profile. The observation of relapse edema is strong evidence of a drug effect. The longevity of these results remains unknown.

5-Year Outcomes of Descemet Stripping Only in Fuchs Dystrophy.

PURPOSE: To report the 5-year outcomes of the first reported case of bilateral Descemet stripping only (DSO) for Fuchs endothelial corneal dystrophy (FECD) at our center. Visual, biomicroscopic, and confocal microscopic findings are described. METHODS: A retrospective case report. RESULTS: A 55-year-old woman with bilateral FECD was referred with decreased visual acuity and blurred vision that interrupted activities of daily living. She underwent sequential 4-mm DSO procedures 6 months apart, with early postoperative results previously reported. Subjective visual symptoms, visual acuity, and corneal edema were analyzed at 1 month, 3 months, 6 months, 12 months, 2 years, 3 years, and 5 years postoperatively. Best corrected visual acuity of 0.0 (logarithm of the minimum angle of resolution) and corneal clearance were achieved in the third month after the procedure. These results have remained stable in the 5-year follow-up period. CONCLUSIONS: Early postoperative results from DSO surgery are encouraging, but questions remain regarding its longevity. Publication of longer-term outcomes such as this is necessary to establish the validity of this procedure as an intervention for FECD.

Factors Affecting Corneal Organ Culture Contamination: A 6-year Study at the New South Wales Tissue Bank.

PURPOSE: To report the rate of microbial contamination and analyze possible risk factors for contamination of banked corneas stored using the organ culture method. METHODS: Data from the New South Wales Tissue Banks incorporating the Lions NSW Eye Bank, between September 1, 2011, and November 30, 2017, were reviewed retrospectively. All corneas collected during this period and stored in organ culture storage media were tested for microbial contamination. The influence of potential factors on the rate of contamination was analyzed using the χ test and logistic regression using generalized estimating equations. RESULTS: A total of 4410 corneas were included in this study, of which 110 were medium culture positive, representing a microbial contamination rate of 2.5%. The main contaminants were Candida species followed by Staphylococcus species. Corneal tissue collected in summer and autumn had a significantly higher contamination rate (P = 0.006). All other factors studied were not shown to have a statistically significant association with contamination after accounting for within-pair correlation and confounders. CONCLUSIONS: A relatively low contamination rate of 2.5% observed in our study reflects the stringent laboratory protocols, strict donor selection criteria, and high level of experience among staff at the Lions NSW Eye Bank. Our study demonstrated that the season of collection had a strong association with the rate of organ culture contamination. Because Candida species contributed the largest percentage of contamination, specific measures to reduce and eliminate fungal proliferation should be considered by eye banks particularly in warm seasons.

Increased Indoleamine 2,3-Dioxygenase and Quinolinic Acid Expression in Microglia and Müller Cells of Diabetic Human and Rodent Retina.

Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels). Results: Based on morphologic criteria, CD39+/ionized calcium binding adaptor molecule 1(Iba-1+) resident microglia and CD39-/Iba-1+ bone marrow-derived macrophages were present at higher density in T1D (13% increase) and T2D (26% increase) human retinas when compared with controls. The density and brightness of IDO+ microglia were increased in both T1D and T2D human retinas. The intensity of QUIN+ expression on CD39+ microglia and VIM+ Müller cells was greatly increased in both human T1D and T2D retinas. T1D retinas showed a 63% loss of NeuN+ neurons and T2D retinas lost approximately 43% when compared with nondiabetic human retinas. Few QUIN+ microglia-like cells were seen in nondiabetic retinas, but the numbers increased 18-fold in T1D and 7-fold in T2D in the central retina. In T1D rat retinas, the density of IDO+ microglia increased 2.8-fold and brightness increased 2.1-fold when compared with controls. Conclusions: Our findings suggest that IDO and QUIN expression in the retinas of diabetic rats and humans could contribute to the neuronal degeneration that is characteristic of diabetic retinopathy.

Descemetorhexis Without Grafting for Fuchs Endothelial Dystrophy-Supplementation With Topical Ripasudil.

PURPOSE: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases. METHODS: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months. Cases failing to clear by month 2 were considered for salvage treatment. This consisted of treatment with 1 of 2 formulations of Rho-associated kinase inhibitor eye drops. Endothelial keratoplasty was planned as the final salvage procedure in unsuccessful cases. RESULTS: Nine of 12 eyes cleared spontaneously between 2 and 6 months. One eye failed to clear by month 5 and topical Y-27632 was administered, without success. Endothelial keratoplasty was performed. In 2 eyes, healing stalled at 3 and 2 months. In both cases, topical ripasudil administered 6 times a day for 2 weeks resulted in complete corneal clearance. In cases achieving corneal clearance, best spectacle corrected visual acuity improved from a mean of 0.26 to 0.125 (logMAR) with subjective improvement in quality of vision. CONCLUSIONS: In Fuchs dystrophy with visual degradation due to central guttae, descemetorhexis without grafting is a viable procedure for visual rehabilitation. Careful patient selection is required, but the advent of topical ripasudil as a salvage agent suggests that a broader application of the surgery may be possible. Further study into the use of this agent is now needed.

The use of donor scleral patch in ophthalmic surgery.

Scleral tissue has been in use in ophthalmology for many years although indications for use have varied. We retrospectively reviewed scleral transplant tissue requests over a 12 month period at a local eye bank and confirmed a small but significant demand for the use of scleral tissue. Iatrogenic surgical complications are the primary indication for use. Our understanding of the indications and outcomes of scleral graft procedures is derived from case reports and small cohort series. We reviewed the current literature on existing indications for its use and discuss the relative outcomes. To our knowledge this represents the first review of scleral transplant indications and further summarises usage rates in the Lions NSW Eye Bank which may provide practical information for those surgeons who use scleral tissue and Eye Banks who supply it.

Implementation of Organ Culture storage of donor corneas: a 3 year study of its impact on the corneal transplant wait list at the Lions New South Wales Eye Bank.

Organ Culture corneal storage offers an extended storage time and increased donor pool and tissue assessment opportunities. In September 2011, the Lions New South Wales Eye Bank (LNSWEB) moved from hypothermic storage to Organ Culture corneal storage. This study evaluates the impact of implementation of Organ Culture on donor eye retrieval and the corneal transplant waiting list over a 3 year period in NSW, Australia. Retrospective review of the LNSWEB data from September 2011 to August 2014. Tissue collection, waiting list and tissue utilization data were recorded. The data from September 2008 to August 2011 for Optisol-GS storage was used for comparison. The annual donor and cornea collection rate increased 35 % and 44 % respectively with Organ Culture compared to Optisol-GS storage. The utilization rate of corneal tissue increased from 73.4 % with hypothermic storage to 77.2 % with Organ Culture storage. The transplant wait list decreased by 77.3 % from September 2011 to August 2014 and correlated with the increased rate of corneal transplantation (r = -0.9381, p < 0.0001). No other factors impacting the wait list changed over this period. Corneas not used from either storage method were due to unacceptable endothelial cell density/viability. The contamination rate of corneas stored in Organ Culture medium was low at 1.74 %. The Organ Culture storage method increases the corneal donor pool available to Eye banks. The practical benefits of the extended storage time and increased donor assessment opportunities have directly led to an increase in corneal utilization rate and a significant decrease in recipient wait list time.

Descemetorhexis for Fuchs' dystrophy.

OBJECTIVE: To describe 2 cases of spontaneous corneal clearing after Descemetorhexis: 1 after iatrogenic trauma (Case 1) and 1 as an intentional surgical intervention for Fuchs endothelial dystrophy (Case 2). METHODS: Retrospective case reports. RESULTS: Full corneal clarity was observed to restore at approximately 1 month after surgery in both cases. Central endothelial cell counts were recorded as 753 and 731 cells/mm(2) in cases 1 and 2, respectively, at last follow-up. Best spectacle corrected visual acuity (BSCVA) at was 6/6 in both cases at 6 weeks and is retained at 9 months. CONCLUSIONS: Selective Descemetorhexis may offer visual rehabilitation without the need for a graft in select cases of Fuchs endothelial dystrophy. Descemetopexy in anticipation of corneal clearing is a viable initial strategy in cases of iatrogenic Descemet trauma with detachment.