Search

Supplemental Digital Content is Available in the Text.

IMPORTANCE: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. OBJECTIVE: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. INTERVENTIONS: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. MAIN OUTCOMES AND MEASURES: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. RESULTS: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (−103 [−196 to −9] cells/mm2), lower screening ECD (−234 [−331 to −137] per 500 cells/mm2), recipient diagnosis of PACE (−257 [−483 to −31] in cells/mm2), and operative complications (−324 [−516 to −133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. CONCLUSIONS AND RELEVANCE: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

IMPORTANCE: Demonstrating that success of Descemet stripping automated endothelial keratoplasty is similar across donor cornea preservation times (PTs) could increase the donor pool. OBJECTIVE: To determine whether the 3-year rate of graft success using corneal donor tissue preserved 8 to 14 days is noninferior to that of donor tissue preserved 7 days or less. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-masked, randomized noninferiority clinical trial was conducted from April 16, 2012, to June 5, 2017, at 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 1090 individuals (1330 study eyes) underwent Descemet stripping automated endothelial keratoplasty (1255 eyes [94.4%] for Fuchs endothelial corneal dystrophy). INTERVENTIONS: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with a PT of 7 days or less (0-7d PT) or 8 to 14 days (8-14d PT). MAIN OUTCOMES AND MEASURES: Graft success at 3 years. RESULTS: Of the 1090 participants (1330 study eyes; 60.2% women and 39.8% men; median age at enrollment, 70 years [range, 42-90 years]), the 3-year cumulative probability of graft success was 95.3% (95% CI, 93.6%-96.9%) in the 0-7d PT group and 92.1% (95% CI, 89.9%-94.2%) in the 8-14d PT group (difference, 3.2%). The upper limit of the 1-sided 95% CI on the difference was 5.4%, exceeding the prespecified noninferiority limit of 4%. The difference was mostly owing to more primary donor failures in the 8-14d PT group, with the conditional probability of failure after the first month being 2.4% in the 0-7d PT group and 3.1% in the 8-14d PT group. In preplanned secondary analyses, longer PT was associated with a lower rate of graft success (unadjusted hazard ratio for graft failure per additional day of PT, 1.10; 95% CI, 1.03-1.18; P = .008 [PT analyzed as days]), with success rates of 96.5% (95% CI, 92.3%-98.4%) for PT of 4 days or less, 94.9% (95% CI, 92.5%-96.6%) for PT of 5 to 7 days, 93.8% (95% CI, 91.0%-95.8%) for PT of 8 to 11 days, and 89.3% (95% CI, 84.4%-92.7%) for PT of 12 to 14 days (P = .01 [PT analyzed as categorical variable]). CONCLUSIONS AND RELEVANCE: The 3-year success rate in eyes undergoing Descemet stripping automated endothelial keratoplasty was high irrespective of PT. However, the study was unable to conclude that the success rate with donor corneas preserved 8 to 14 days was similar to that of corneas preserved 7 days or less with respect to the prespecified noninferiority limit. Although longer PT was associated with a lower success rate, the difference in rates was small when PT was less than 12 days. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01537393

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

Supplemental Digital Content is Available in the Text.

OBJECTIVE To define the relationship between Fuchs endothelial corneal dystrophy (FECD) severity and central corneal thickness (CCT). METHODS We examined 1610 eyes from a subset of index cases, family members, and unrelated control subjects with normal corneas from the FECD Genetics Multi-Center Study. To estimate the association between FECD severity grade (7-point severity scale based on guttae confluence) and CCT measured by ultrasonographic pachymetry, a multivariable model was used that adjusted for eye, age, race, sex, history of glaucoma or ocular hypertension, diabetes mellitus, contact lens wear, intraocular pressure, and familial relationship to the index case. An interaction between FECD severity grade and edema (stromal or epithelial) on slitlamp examination findings was used to investigate whether the effect of FECD severity grade on CCT differed between those with and without edema. RESULTS Average CCT was thicker in index cases for all FECD grades compared with unaffected controls (P ≤ .003) and in affected family members with an FECD grade of 4 or greater compared with unaffected family members (P ≤  .04). Similar results were observed for subjects without edema. Average CCT of index cases was greater than that of affected family members with grades 4, 5, and 6 FECD (P ≤ .02). Intraocular pressure was also associated with CCT (P = .01). CONCLUSIONS An increase in CCT occurs with increasing severity of FECD, including at lower FECD grades in which clinically observable edema is not present. Monitoring CCT changes serially could be a more sensitive measure of disease progression with surgical therapeutic implications.

Two patients developed Acanthamoebakeratitis 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, Acanthamoebaspecies 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.

• Previous controlled studies on contact lens-associated ulcerative keratitis were performed before the widespread use of disposable contact lenses. Therefore, a controlled study was undertaken to determine the relative risk of ulcerative keratitis among users of disposable soft contact lenses compared with the risk among users of other lens types. Forty-six consecutive cases of contact lens-associated ulcerative keratitis were identified between January 1990 and June 1992 at a corneal specialty practice in western Michigan. Five controls, matched to each case patient according to the dispensing date and prescribing practitioner, were obtained for 42 cases (91%). Users of dailywear rigid gas-permeable lenses had the lowest risk of developing ulcerative keratitis. Relative to users of daily-wear soft contact lenses, users of extended-wear soft contact lens had an age-adjusted and sex-adjusted relative risk of 1.87 (95% confidence interval, 0.61 to 5.71). Disposable soft contact lens users had the highest risk of developing ulcerative keratitis, with an adjusted relative risk of 14.16 (95% confidence interval, 5.47 to 37.63) compared with daily-wear soft contact lens users and 7.66 (95% confidence interval, 2.27 to 25.83) compared with conventional extended-wear soft contact lens users.

OBJECTIVE: To assess the relative risk of contact lens—associated ulcerative keratitis by lens type and related lenswearing behavior. DESIGN: Case-control study. SETTING/PARTICIPANTS: Forty practice-based case patients with contact lens—associated ulcerative keratitis and 180 control patients matched to the case patients' dispensing practitioner and date of contact lens prescription. RESULTS: Compared with users of daily-wear soft lenses, users of disposable soft contact lenses had a 13.33-fold (95% confidence interval [CI], 5.35 to 33.20) excess risk of ulcerative keratitis. However, after adjusting for overnight wear, the excess risk associated with disposable contact lenses is reduced to 3.21 (95% CI, 1.22 to 14.36). Overall, overnight wear of contact lenses conferred an 8.25-fold excess risk (95% CI, 3.33 to 25.58) of ulcerative keratitis after controlling for lens type. No protective effect of standard compared with substandard lens hygiene was found. The risk of ulcerative keratitis attributable to overnight wear was estimated at 49% for users of daily-wear lenses and 74% for users of lenses approved for overnight wear. CONCLUSION: Overnight wear of contact lenses is the overwhelming risk factor for ulcerative keratitis among contact lens users. We estimate that 49% to 74% of cases of contact lens—associated ulcerative keratitis could be prevented by eliminating overnight wear.

IN REPLY The findings summarized in our report1 are not scientifically controversial. While epidemiologic research does not provide a conclusive causal linkage, such research approaches causality in these circumstances: (1) The effect or magnitude of the risk estimated is very large. The relative risks associated with overnight wear are of the same magnitude as those that have associated smoking with lung cancer. (2) The major findings are replicated in studies using different designs and in different locations. The magnitude and direction of our findings are remarkably similar to those of previous studies performed in the United States and England.2-4 (3) The findings are biologically plausible. With currently available contact lenses, the relative amount of corneal hypoxia that occurs with over-night wear has been well documented and the findings have been recently expanded and reconfirmed.5Nevertheless, despite the absence of "scientific controversy" about the principal findings of our

Division of Ophthalmology, Department of Surgery, Michigan State University College of Human Medicine (GRAMEC), Butterworth and Saint Mary's 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.

IN REPLY. —We agree with Levy that the selection of suitable controls is the most difficult and most important aspect in the design of a case-control study. His main objection to our study design is that we did not match our cases and controls with regard to contact lens wear schedule. This was intentional, since we were not primarily interested in the lens material itself as a risk factor for ulcerative keratitis in isolation from the interaction of patients with contact lens products. Rather, we were interested primarily in the more clinically relevant question of the risk of ulcerative keratitis among users of different contact lens types.In a case-control study, cases and controls are compared with respect to the attributes or exposures thought to be related to the disease under consideration. Controls should ideally be matched to cases in all respects except for the risk factor(s) of interest. Any