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Purpose To determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. Design Retrospective cohort study. Participants Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. Methods Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. Main Outcome Measures The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. Results A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years ( P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases ( P = 0.056). Conclusions Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified.

Purpose: To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. Methods: All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. Results: Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90–1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). Conclusions: DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity. Keywords: Corneal endothelium, DMEK, Diabetes mellitus, Descemet membrane, Endothelial keratoplasty, Corneal transplantation

The purpose of this study was to determine the in vitro and ex vivo susceptibility of human corneal cells to West Nile virus (WNV) infection and evaluate the ability of the virus to disseminate to the corneas of infected mice. Human corneal epithelial cells were challenged with WNV, incubated for 1–6 days, and tested for evidence of WNV infection. Viral RNA and antigen were detected at every time point, and the virus reached a peak titer of 2.5 × 107 plaque-forming units (pfu)/mL at 3 days postinoculation (PI). Corneas procured from donors were incubated in culture dishes containing WNV for 1–5 days and tested for evidence of WNV. Viral RNA and antigen were detected, and the virus reached a mean peak titer of 4.9 × 104 pfu/mL at 5 days PI. Mice were inoculated intraperitoneally with WNV, and their eyes were harvested at 2, 5, and 8 days PI and tested for evidence of WNV. Viral RNA was detected in corneas of four of nine systemically infected mice as early as 2 days PI. We conclude that human corneal cells support WNV replication in vitro and ex vivo, and WNV may disseminate into the corneas of experimentally infected mice. These findings indicate that corneal transmission cannot be ruled out as a novel mode of human-to-human WNV transmission and additional experiments should be conducted to assess this risk further.

Purpose To compare the incidence of visually significant postoperative cystoid macular edema (CME) in pseudophakic eyes after Descemet membrane endothelial keratoplasty (DMEK) performed after recent versus remote cataract surgery. Methods A retrospective chart review was performed of all consecutive eyes that underwent DMEK without concurrent cataract surgery at the University of Iowa between October 2012 and December 2014. The DMEK procedures were classified as staged if performed between 2 weeks and 6 months after cataract surgery and solitary if performed more than 6 months after cataract surgery. Possible confounders, including a history of diabetes in the recipient, were tracked. Macular optical coherence tomography was performed to detect CME 1 month after DMEK if the best-corrected visual acuity was ≤20/30 with a clear cornea with no other reason for visual compromise. Results A total of 173 eyes from 140 patients were included in the statistical analysis. Staged DMEK was performed in 88 eyes (50.8%) and solitary DMEK in 85 eyes (49.2%). The incidence of CME was 8.0% (7 of 88 eyes) in the staged DMEK group and 7.1% (6 of 85 eyes) in the solitary DMEK group (P = 0.823). The incidence of CME did not differ significantly between the staged and solitary DMEK groups regardless of the recipient diabetic status. All cases of CME resolved within 6 months on topical therapy. Conclusions The incidence of postoperative CME after DMEK is similar in the setting of recent or remote cataract surgery.

PURPOSE: To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter randomized clinical trial. METHODS: 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0–7 days (N=675) or 8–14 days (N=655) and followed for three years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection. RESULTS: Cumulative probability of definite graft rejection was 3.6% (99% CI 2.5% to 5.3%). Younger recipient age was associated with graft rejection [p0.01). Among clear grafts with an ECD measurement at baseline and 3 years (N=913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (N=27) than in those that did not (N=886) (48% vs 38%, p=0.03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS. CONCLUSIONS: Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure.

To evaluate the outcome of the Boston type 1 keratoprosthesis (KPro-1) in eyes with iridocorneal endothelial syndromes and failed keratoplasties.A retrospective review was performed of every eye with a history of iridocorneal endothelial syndrome and a failed corneal transplant that was treated with a KPro-1 at a tertiary eye care center between January 1, 2008, and July 1, 2014. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications.Four eyes met the inclusion criteria. Two eyes had essential iris atrophy and 2 eyes had Chandler syndrome. All 4 eyes had failed corneal transplants and successful glaucoma drainage devices. The mean patient age at the time of KPro-1 surgery was 68.3 years (range, 60-80 years). The mean postoperative follow-up duration was 47 months (range, 27-69 months). Preoperatively, the best-corrected visual acuity (BCVA) was worse than 20/200 in all 4 eyes, including 2 eyes that had hand motions vision. After KPro-1, all 4 eyes initially obtained a BCVA of ≥20/70. At the most recent examination, the BCVA was still ≥20/100 in 3 eyes. The KPro-1 device was retained in all 4 eyes. Postoperative complications included glaucoma progression (1 eye), a retroprosthetic membrane (1 eye), and sterile vitritis (1 eye).The Boston KPro-1 may offer a better prognosis than repeat traditional keratoplasty in reestablishing corneal clarity in eyes with iridocorneal endothelial syndromes. Despite anatomic success, visual rehabilitation may be compromised by preexisting glaucomatous optic neuropathy and its postoperative progression.

The purpose of this study was to evaluate the outcomes of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed keratoplasty. A retrospective review was performed of every patient treated with a Kpro-1 at a tertiary eye care center between January 1, 2008 and July 1, 2013. Eyes with a failed keratoplasty originally performed for corneal edema, trauma, or keratoconus were included in the statistical analysis. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. Twenty-four eyes met the inclusion criteria, including 13 eyes with corneal edema, 8 eyes with trauma, and 3 eyes with keratoconus. After a mean follow-up period of 28.9 months (range 7-63 months), the median best corrected visual acuity (BCVA) was 20/125. The BCVA was ≥ 20/40 in 4 (16.7 %) eyes, ≥ 20/70 in 9 (37.5 %) eyes, and ≥ 20/200 in 14 (58.3 %) eyes. Overall, the postoperative BCVA improved in 17 (70.9 %) eyes, was unchanged in 3 (12.5 %) eyes, and was worse in 4 (16.7 %) eyes. The initial Kpro-1 was retained in 22 (91.7 %) eyes, and was successfully repeated in the other 2 eyes. One or more serious prosthesis- or sight-threatening complications occurred in 8 (33.3 %) eyes. These included 1 case of wound dehiscence leading to prosthesis extrusion, 1 case of fungal keratitis leading to prosthesis extrusion, 4 cases of endophthalmitis, and 5 retinal detachments. The Boston Kpro-1 is associated with an excellent prognosis for prosthesis retention and satisfactory visual improvement in eyes with previous failed keratoplasty.

Purpose To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). Methods A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. Results A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. Conclusions We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

The aim of this study was to evaluate preparation outcomes of tissue prepared for Descemet membrane endothelial keratoplasty (DMEK) from diabetic and nondiabetic donors.In this nonrandomized, consecutive case series, DMEK grafts were prepared from diabetic and nondiabetic donors by experienced technicians in 2 eye banks using slightly different, modified submerged manual preparation techniques to achieve "prestripped" graft tissue. Graft preparation results were analyzed retrospectively. The main outcome measure was the rate of unsuccessful (failed) DMEK graft preparations, defined as tears through the graft area that prevent tissue use.A total of 359 corneas prepared from 290 donors (114 diabetic and 245 nondiabetic) were included in the statistical analysis of graft preparation failure. There were no significant differences between diabetic and nondiabetic donor tissue characteristics with respect to donor age, death to preservation time, death to preparation time, endothelial cell density, percent hexagonality, or coefficient of variation. DMEK tissue preparation was unsuccessful in 19 (5.3%) cases. There was a significant difference in the site-adjusted rate of DMEK preparation failure between diabetic [15.3%; 95% confidence interval (CI), 9.0-25.0] and nondiabetic donors (1.9%; 95% CI, 0.8-4.8), and the corresponding site-adjusted odds ratio of DMEK graft preparation failure in diabetic donor tissue versus nondiabetic donor tissue was 9.20 (95% CI, 2.89-29.32; P = 0.001).Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

PURPOSE To determine the visual outcomes, device retention, and complications after Boston type 1 keratoprosthesis (KPro-1) device implantation. METHODS Comprehensive review of every case of KPro-1 implantation at a tertiary eye care center. RESULTS The initial KPro-1 procedure, performed in 75 eyes without a previous keratoprosthesis, was included in the analysis. During the first 6 postoperative months, improvement occurred in the mean preoperative best-corrected visual acuity of 20/1265 to a mean best-obtained postoperative visual acuity of 20/97 (P < 0.001). After a mean follow-up period of 41.4 months (range, 0.8-82.8 months), the final mean best-corrected visual acuity was 20/428. Improved vision was recorded in 43 eyes (57.3%), ambulatory vision (≥20/400) in 47 eyes (62.7%), intermediate functional vision (≥20/80) in 23 eyes (30.7%), and full functional vision (≥20/40) in 11 eyes (14.7%). The initial device was retained in 64 eyes (85.3%), with a Kaplan-Meier retention probability of 96% at 6 months and 82% at 5 years. One or more sight-threatening complications occurred in 51 eyes (68%). These included device extrusion in 11 eyes (14.7%), ulcerative keratitis in 12 eyes (16%), endophthalmitis in 7 eyes (9.3%), sterile vitritis in 3 eyes (4%), retroprosthetic membranes in 25 eyes (33.3%), maculopathy in 26 eyes (34.7%), retinal detachment in 9 eyes (12%), and progressive optic neuropathy in 7 eyes (9.3%). CONCLUSIONS Boston KPro-1 implantation is associated with satisfactory visual outcomes and excellent device retention in a majority of cases. However, serious postoperative complications are common and may compromise the final visual result.

We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions.Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed.Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78).Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

Background/aims To evaluate the Boston type 1 keratoprosthesis (KPro-1) in treatment of eyes with primary congenital glaucoma. Methods A retrospective review was performed of every eye with congenital glaucoma that was treated with a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014. The main outcome measures were visual outcome, prosthesis retention and postoperative complications. Results Six eyes of six patients met the inclusion criteria. This included two paediatric patients, aged 6 months and 6 years, and four adults who were 27–33 years of age. Preoperatively, the best corrected visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand motions and one eye had light perception vision. After a mean follow-up period of 31 months (range 16–51 months), three eyes (50.0%) had a BCVA that was ≥20/400. Overall, the BCVA improved in four eyes (66.7%), and remained the same in two eyes (33.3%). The device was retained in six eyes (83.3%). One or more complications occurred in five eyes (83.3%) and included sterile corneal ulceration (three eyes), retroprosthetic membrane formation (three eyes), progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye) and an epiretinal membrane (one eye). Conclusions The Boston KPro-1 has an excellent prognosis for retention in eyes with congenital glaucoma. The visual prognosis remains guarded due to the high prevalence of pre-existing ocular comorbidity and the common occurrence of sight-threatening postoperative complications.