David D. Verdier

A randomized trial of intraocular lens fixation techniques with penetrating keratoplasty

PURPOSE Pseudophakic corneal edema is the principal indication for penetrating keratoplasty in the United States. Currently, three techniques of intraocular lens (IOL) fixation during penetrating keratoplasty for this condition are commonly used--flexible anterior chamber IOL (AC IOL) implantation, iris suture fixation of a posterior chamber IOL (PC IOL), and transscleral suture fixation of a PC IOL. This study represents the first prospective, randomized comparison of these three techniques. METHODS One hundred seventy-six consecutive patients with pseudophakic corneal edema who underwent penetrating keratoplasty with IOL exchange were randomized to one of the three implantation techniques. Standardized evaluations were performed at baseline and at 6, 12, and 18 months postoperatively. Life-table analysis provided cumulative risk estimates for specific complications. RESULTS Randomization produced comparable groups at baseline. The cumulative risk of macular edema was significantly less for the iris fixation cohort than for either the AC IOL or scleral fixation group. A complications index was constructed based on the major adverse outcomes of glaucoma escalation, cystoid macular edema, IOL dislocation, and graft failure. A significantly lower risk of complication was found for iris compared with scleral fixation of PC IOLs. CONCLUSION The authors conclude that transscleral fixation of the PC IOL at the time of penetrating keratoplasty for pseudophakic corneal edema is associated with a greater risk of adverse outcome than iris fixation of a PC IOL.

A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability

Purpose: To describe the methods for family and case–control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD). Methods: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry. Results: Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib–sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness. Conclusions: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

Report of the eye bank association of America medical advisory board subcommittee on fungal infection after corneal transplantation

Purpose: To investigate the incidence of fungal infections after corneal transplantation to determine whether storage media supplementation with an antifungal should be considered. Methods: Adverse reactions reported to the Eye Bank Association of America through the online adverse reaction reporting system between January 1, 2007, and December 31, 2010, were reviewed to identify cases of recipient fungal infection. Data were collected regarding the donor, the donor cornea, recovery and processing, and mate culture and clinical course of the recipients. Results: Thirty-one cases of culture-proven fungal keratitis (n = 14) and endophthalmitis (n = 17) were reported out of 221,664 corneal transplants performed using corneal tissue distributed by domestic eye banks (1.4 cases per 10,000 transplants performed). Although the annual incidence of postkeratoplasty fungal infection has not increased significantly since 2005, a trend toward an increasing rate of fungal infection has been observed. Fungal infections were more commonly reported after endothelial keratoplasty procedures (0.022%) than penetrating keratoplasty procedures (0.012%), but the difference was not statistically significant (P = 0.076). Additionally, no association was found between fungal infection after endothelial keratoplasty and whether the lamellar tissue cut was performed by the surgeon or the eye bank technician. Seventy-three percent (16 of 22) of the fungal cultures performed on the mate corneas were positive, with infection developing in 67% (10 of 15) of recipient eyes (endophthalmitis in 6 eyes and keratitis in 4 eyes). Conclusions: Although a nonsignificant increasing trend in the rate of fungal infection has been observed over the past 6 years, it is not sufficiently compelling to pursue antifungal supplementation of donor storage media.

Effect of donor and recipient factors on corneal graft rejection

Purpose: To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty in the Cornea Donor Study. Methods: Overall, 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models. Results: Eyes with pseudophakic or aphakic corneal edema (n = 369) were more likely to experience a rejection event than eyes with Fuchs dystrophy (n = 676) [34% ± 6% vs. 22% ± 4%; hazard ratio = 1.56; 95% confidence interval (CI), 1.21–2.03]. Among eyes with Fuchs dystrophy, a higher probability of a rejection event was observed in phakic posttransplant eyes compared with those that underwent cataract extraction with or without intraocular lens implantation during penetrating keratoplasty (29% vs. 19%; hazard ratio = 0.54; 95% CI, 0.36–0.82). Female recipients had a higher probability of a rejection event than male recipients (29% vs. 21%; hazard ratio = 1.42; 95% CI, 1.08–1.87) after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection. Conclusions: There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared to that in eyes with Fuchs dystrophy. Female recipients were more likely to have a rejection event than male recipients. Graft rejection was not associated with donor age.

Cornea preservation time study: methods and potential impact on the cornea donor pool in the United States.

Purpose: The aim of this study was to describe the aims, methods, donor and recipient cohort characteristics, and potential impact of the Cornea Preservation Time Study (CPTS). Methods: The CPTS is a randomized clinical trial conducted at 40 clinical sites (70 surgeons) designed to assess the effect of donor cornea preservation time (PT) on graft survival 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were randomized to receive donor corneas stored ⩽7 days or 8 to 14 days. Donor and patient characteristics, tissue preparation and surgical parameters, recipient and donor corneal stroma clarity, central corneal thickness, intraocular pressure, complications, and a reading center-determined central endothelial cell density were collected. Surveys were conducted to evaluate pre-CPTS PT practices. Results: The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median eye bank–determined screening endothelial cell density of 2688 cells/mm2, and 74% eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240 bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18% diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for DSAEK in 2010 to 2011; 96% were preserved ⩽7 days. Of 305 American Academy of Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their maximum PT preference at 8 days or less. Conclusions: The CPTS will increase understanding of factors related to DSAEK success and, if noninferiority of longer PT is shown, will have great potential to extend the available pool of endothelial keratoplasty donors. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01537393.

Multiple Chalazia and Rosacea in a Patient Treated with Amiodarone

Division of Ophthalmology, Department of Surgery, Michigan State University College of Human Medicine (GRAMEC), Butterworth and Saint Marys Hospitals, Blodgett Memorial Medical Center and the Western Michigan Ambulatory Surgical Center (D.M.R., D.D.V.); the Departments of Pathology (C.L.D.) and Division of Cardiology, Department of Internal Medicine (V.E.W.), Butterworth Hospital; and the Division of Cardiology, Cleveland Metropolitan General Hospital and Case Western Reserve University School of Medicine (N.D.M.). This study was supported in part by a grant from Wyeth Laboratories.

Corneal thickness as a predictor of corneal transplant outcome.

Purpose: To assess corneal thickness (CT) and correlation with graft outcome after penetrating keratoplasty in the Cornea Donor Study. Methods: A total of 887 subjects with a corneal transplant for a moderate-risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) had postoperative CT measurements throughout a 5-year follow-up time. Relationships between baseline (recipient, donor, and operative) factors and CT were explored. Proportional hazards models were used to assess the association between CT and graft failure. Relationship between CT and cell density was assessed with a longitudinal repeated measures model and Spearman correlation estimates. Results: Higher longitudinal CT measurements were associated with the following: diagnosis of pseudophakic or aphakic corneal edema (P < 0.001), intraocular pressure >25 mm Hg during the first postoperative month (P = 0.003), white (non-Hispanic) donor race (P = 0.002), and respiratory causes of donor death (P < 0.001). Among those without graft failure within the first postoperative year, the 5-year cumulative incidence (±95% confidence interval) of graft failure was 5% ± 5% in those with a 1-year CT ⩽500 &mgr;m, 5% ± 3% for CT 501 to 550 &mgr;m, 7% ± 4% for CT 551 to 600 &mgr;m, and 20% ± 11% for CT >600 &mgr;m. In a multivariate analysis, both 1-year CT and cell density were associated with subsequent graft failure (P = 0.002 and 0.009). CT increase was modestly associated with endothelial cell loss during follow-up (r = −0.29). Conclusions: During the first 5 years after penetrating keratoplasty, CT can serve as a predictor of graft survival. However, CT is not a substitute for cell density measurement because both measures were independently predictive of graft failure.

Acanthamoeba keratitis associated with disposable contact lenses.

Two patients developed Acanthamoeba keratitis associated with the use of disposable extended-wear hydrogel contact lenses. Both patients removed, irrigated, and reinserted the contact lenses without disinfecting them. One patient wore the lenses on a daily basis, rinsed the lenses in tap water, stored them overnight, and discarded them weekly. Both infections were treated successfully. In a third patient, Acanthamoeba species was cultured from two pairs of disposable lenses that had been stored in cases rinsed with well water. Potential benefits from disposable contact lens wear are negated when patients do not comply with a continuous wearing schedule.

Randomized, prospective, single-masked clinical trial of endothelial keratoplasty performance with 2 donor cornea 4°C storage solutions and associated chambers.

Purpose: The aim of this study was to compare endothelial cell loss and graft success 6 months after endothelial keratoplasty (EK) with paired donor corneas stored in Optisol GS and Life4°C solutions and their associated storage chambers. Methods: Donor pairs were stored, one in Optisol GS and the other in Life4°C, and prepared for Descemet stripping automated EK or Descemet membrane EK. Matched pairs of recipients with Fuchs dystrophy were randomized to 1 member of each donor pair. Clarity of recipient stroma, intraocular pressure, and complications were followed for 6 months. Central endothelial images of the donor cornea at screening and 3 and 6 months after EK were analyzed by a masked central reading center. Dual grading of endothelial cell density was performed using the center method. Differences in endothelial cell density and cell loss were examined by paired analysis. Results: Thirty-two pairs were enrolled, and 27 were analyzed (5 had improper matching or loss to follow-up). Donor age was 59 ± 14 years, median death-to-surgery time was 4 days (range, 2–9 days), 6 recipient pairs had Descemet membrane EK, and 21 had Descemet stripping automated EK. Recipient age was comparable in the Optisol GS and Life4°C groups (70 vs. 68 years, respectively, P = 0.46). Six-month central endothelial cell loss did not differ significantly between the Life4°C and Optisol GS groups (18 ± 18% vs. 20 ± 20%, respectively, P = 0.55). All recipient corneas were clear at 6 months in both groups. Conclusions: Endothelial cell loss and graft success were comparable at 6 months for paired donor corneas stored in Optisol GS and Life4°C. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657500.

Corneal Endothelial Cell Loss 3 Years After Successful Descemet Stripping Automated Endothelial Keratoplasty in the Cornea Preservation Time Study: A Randomized Clinical Trial

Importance Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty. Objective To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT. Design, Setting, and Participants A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 945 eyes of 769 participants were included in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK, performed primarily for Fuchs endothelial corneal dystrophy (96% of the cohort). The study was conducted from April 16, 2012, to June 5, 2017. Interventions DSAEK with random assignment of a donor cornea with PT of 0 to 7 days (0-7d PT) or 8 to 14 days (8-14d PT). Main Outcomes and Measures Endothelial cell density (ECD) at 3 years determined by a central image analysis reading center from clinical specular or confocal central endothelial images. Results Nine hundred forty-five eyes of 769 participants (median age, 70 years [range, 42-90 years], 60.8% women, 93.0% white) in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK were included. At the initial eye bank tissue screening, mean (SD) central ECD was 2746 (297) cells/mm2 in the 0-7d PT group (n = 485) and 2723 (284) cells/mm2 in the 8-14d PT group (n = 460). At 3 years, the mean (SD) ECD decreased from baseline by 37% (21%) in the 0-7d PT group and 40% (22%) in the 8-14d PT group to 1722 (626) cells/mm2 and 1642 (631) cells/mm2, respectively (mean difference, 73 cells/mm2; 95% CI, 8-138 cells/mm2; P = .03). When analyzed as a continuous variable (days), longer PT was associated with lower ECD (mean difference by days, 15 cells/mm2; 95% CI, 4-26 cells/mm2; P = .006). Endothelial cell loss (ECL) was comparable from 4 to 13 days’ PT (n = 878; 36%-43% when tabulated by day). Available extension study ECD results at 4 years mirrored those at 3 years in the 203 eyes in the 0-7d PT group (mean [SD] ECD, 1620 [673] cells/mm2 and mean [SD] ECL, 41% [23%]) and 209 eyes in the 8-14d PT group (mean [SD] ECD, 1537 [683] cells/mm2 and mean [SD] ECL, 44% [23%]) (mean difference, 112 cells/mm2; 95% CI, 5-219 cells/mm2; P = .04). Conclusions and Relevance Although ECL 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer PT, the effect of PT on ECL is comparable from 4 to 13 days’ PT. Trial Registration clinicaltrials.gov Identifier: NCT01537393