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Objective To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study. Design Multicenter, prospective, double-masked, controlled clinical trial. Participants One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States. Methods Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD. Main Outcome Measures Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. Results There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, −10% to 6%; unadjusted P = 0.60). Baseline ECD ( P = 0.71), 10-year ECD ( P > 0.99), and changes in ECD over 10 years ( P = 0.86) were similar comparing donor groups with and without diabetes. Conclusions The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP). Design: Multicenter, prospective, double-masked clinical trial. Participants: We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). Methods: Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). Main Outcome Measures: Endothelial cell density at 10 years. Results: Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm2 (interquartile range [IQR], 522–850 cells/mm2), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm2 (IQR, 483–694 cells/mm2; P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P < 0.001) and larger donor tissue size (P < 0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm2 at 10 years and only 24 (14%) had an ECD of >1000 cells/mm2. Conclusions: Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Onchocercal keratitis (river blindness) is one of the leading worldwide causes of blindness. Light microscopic analysis of human specimens and corneal tissue from experimental models has implicated the eosinophil as an important cell in the inflammatory response. Our previous studies in experimental murine onchocercal keratitis have demonstrated that the inflammatory infiltrate is composed primarily of eosinophils displaying ring shaped or bilobed nuclei. However, a number of cells were not characterizable by light microscopy, presumably due to mechanical distortion. To more fully characterize the inflammatory cell infiltrate, we examined corneal specimens by transmission electron microscopy. In addition to typical eosinophils with bilobed and ring shaped nuclei, this approach revealed cells with variable nuclear morphology and cell shape which contained the dense cored granules characteristic of eosinophils. Hence, the degree of pleomorphism of eosinophils is broader than appreciated and underscores the importance of this cell in experimental murine onchocercal keratitis. [ABSTRACT FROM AUTHOR]

Purpose: To report three cases of acute corneal edema occurring decades after penetrating keratoplasty (PK) for keratoconus in eyes wearing scleral contact lenses (ScCLs) with previously clear corneal grafts.Methods: Retrospective chart review of three ScCL wearers presenting for sudden onset pain and blurred vision. Data extracted included clinical presentation, year and reason for PK, ocular medications and comorbidities, contact lens wearing history, results of any ancillary testing available including corneal topography, anterior segment optical coherence tomography (OCT), and specular microscopy surrounding the event, treatment and outcomes of intervention. The number of PK eyes fit with ScCLs in the author's practice was determined to estimate the prevalence of this event.Results: The three patients each had a longstanding PK for keratoconus performed between 33-35 years prior to presentation and recurrent ectasia. Each patient presented with an acute, painful eye and reduced vision either 3 days, 4 months or 9 years after refitting into ScCLs. Each eye had well demarcated focal microcystic epithelial and stromal edema within the graft and crossing the wound margin onto the host cornea. Although a definitive break or detachment of Descemet's membrane was not visualized, the presentations suggest these were episodes of acute hydrops.Conclusions: Longstanding PKs with recurrent ectasia and acute focal edema suggestive of corneal hydrops is demonstrated in this case series of ScCL wearers. Although similar events have occurred as part of the natural history of post-PK corneas for keratoconus, the proximity of ScCL refitting to two of the events suggests some association. [ABSTRACT FROM AUTHOR]

Purpose: Technological development drives the optimization of therapeutics in ophthalmology, but quantifiable and systematic review of such innovation is lacking. To fill this gap, we characterize trends in ophthalmology-related patents in the United States from 2005 to 2020. Methods: Publicly available patent data from the US Patent and Trademark Office was analyzed with the R programming language. Ophthalmology-related patents were identified with a keyword search of their titles and claims text. Temporal trends were assessed with the Mann–Kendall trend test (α = 0.05, two-sided). Results: Of 4.5 million collected patents, some 21,000 (0.5%) were ophthalmology related. The number of annually granted ophthalmology patents increased over time (Mann–Kendall test: z = 4.91; P < 0.001), from 619 patents released in 2005 to 2,019 patents in 2020. Patent counts also increased over time for all ophthalmic subspecialties except oculoplastics, with steepest rises in retina (z = 4.91; P < 0.001) and cornea (z = 4.64; P < 0.001). The most cited patents were in biocompatible intraocular implants and implantable controlled-release drug delivery systems, which underscores particular advancement in therapeutic efficacy and safety in devices used in the treatment and management of common yet debilitating eye conditions. Conclusion: This exploratory analysis reveals hotspots for ophthalmology-related innovation in the United States that may predict current and future growth trends in device development and pharmacologic advancement in ophthalmology, paving the way for more diverse and effective treatment options for preserving vision. [ABSTRACT FROM AUTHOR]

Highlights a study which established the role for lumican in the regulation of collagen assembly into fibrils, in various connective tissues. Information on lumican; Importance of collagen architecture; Use of mice homozygous for a lumican null mutation; Reference to abnormal collagen fibril morphology; Results of the study; Conclusions drawned based on the study.

Purpose: To determine whether intracameral moxifloxacin 500 [mu]g is noninferior to 250 [mu]g for central endothelial cell loss (ECL) after phacoemulsification. Setting: Aravind Eye Care System. Design: Prospective masked randomized study. Methods: Eyes with bilateral nuclear cataracts, central endothelial cell density (ECD) of more than 2000 cells/mm2, and ECD not differing between eyes by more than 200 cells/mm2 underwent phacoemulsification at least 14 days apart. Intraoperatively, the first eye was randomized to receive either a 500 or 250 [mu]g dose of moxifloxacin intracamerally and received the other dose for the second-eye surgery. Postoperative course was monitored at 1 day, 1 week, 1 month, and 3 months. Preoperative and 30-day and 90-day postoperative central ECD was determined by a reading center for a masked analysis of ECL at 3 months postoperatively. Results: Fifty eyes of 25 patients (aged 48 to 69 years) underwent uneventful surgery and had normal postoperative courses. The point estimate (PE) and 95% CI for the mean difference in % ECL between the 500 [mu]g and 250 [mu]g doses at 3 months postoperatively was 0.8% (-5.8%, 7.4%). Upon identifying and removing 2 outliers, noninferiority was proven with a mean difference of the PE, -2.2% (CI, -6.5%, 2.1%). Conclusions: Clinical and corneal endothelial cell were comparable in this study population for the 250 [mu]g and 500 [mu]g doses of intracameral moxifloxacin. Both doses were well tolerated clinically, supporting the use of the higher dose for improved antimicrobial coverage for the prevention of postoperative endophthalmitis. [ABSTRACT FROM AUTHOR]

Purpose To assess endothelial cell density (ECD) and model 10-year cell loss after Descemet stripping endothelial keratoplasty (DSEK), and to compare with results after penetrating keratoplasty (PK) performed for the same indications in the Cornea Donor Study (CDS). Design Retrospective, longitudinal study. Participants Five hundred ninety DSEK recipients, 21 to 96 years of age, treated for Fuchs' dystrophy (n = 498; 84%), pseudophakic or aphakic corneal edema (n = 89; 15%), or other endothelial dysfunction (n = 3; <1%). Methods Review of 1005 consecutive primary DSEK procedures by 6 surgeons identified 752 grafts (75%) in 590 recipients with ECD measurements at 1 or more postoperative examinations between 6 months and 10 years. Four statistical models applied previously to the CDS PK data were considered. The preferred model (Bayesian Markov chain Monte Carlo) accounted for missing data, selective dropout from graft failure, correlations between fellow eyes, and correlations between longitudinal repeated measures. Main Outcome Measures Central corneal ECD. Results The median donor corneal ECD (25th–75th percentiles) was 3005 cells/mm 2 (2852–3203 cells/mm 2 ) at baseline, 2077 cells/mm 2 (1660–2411 cells/mm 2 ) at 6 months, and 926 cells/mm 2 (617–1433 cells/mm 2 ), with a range from 408 to 2538 cells/mm 2 at 10 years. After median cell loss of 32% in the perioperative period, ECD declined at a linear rate of approximately 110 cells/mm 2 per year between 6 months and 10 years after DSEK. At 10 years, the median cell loss was 71% (53%–80%) relative to the baseline donor ECD, comparable with the 76% (70%–82%) median cell loss after PK by 68 surgeons in the CDS. The 10-year ECD correlated with the 6-month postoperative ECD ( r = 0.56; P < 0.001), but not with the baseline donor ECD ( r = −0.04; P = 0.78). Selective dropout from graft failure did not affect the cell loss model significantly. Conclusions The linear decline in ECD after DSEK was consistent with shorter-term endothelial keratoplasty studies and was distinct from the biexponential cell loss trend characteristic of PK. By 10 years, cell loss was comparable in surviving clear grafts for both DSEK and PK. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age. Design: Multicenter, prospective, double-masked clinical trial. Participants: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years. Methods: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Main Outcome Measures: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months. Results: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, −1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P < 0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6. Conclusions: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To assess 3-year outcomes of Descemet''s stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Cornea Donor Study (CDS). Design: Prospective, multicenter, nonrandomized clinical trial. Participants: A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs'' dystrophy or pseudophakic corneal edema) compared with 1101 subjects undergoing PKP from the CDS. Methods: The DSAEK procedures were performed by 2 experienced surgeons using the same donor and similar recipient criteria as for the CDS PKP procedures, performed by 68 surgeons. Graft success was assessed by Kaplan-Meier survival analysis. Central endothelial cell density (ECD) was determined from baseline donor and postoperative central endothelial images by the reading center used in the CDS Specular Microscopy Ancillary Study. Main Outcome Measures: Graft clarity and ECD. Results: The donor and recipient demographics were comparable in the DSAEK and PKP groups, except that the proportion of Fuchs'' dystrophy cases was higher in the DSAEK cohort. The 3-year survival rate did not differ significantly between DSAEK and PKP procedures performed for either Fuchs'' dystrophy (96% for both; P = 0.81) or non-Fuchs'' cases (86% vs. 84%, respectively; P = 0.41). Principal causes of graft failure or regraft within 3 years after DSAEK and PKP were immunologic graft rejection (0.6% vs. 3.1%), endothelial decompensation in the absence of documented rejection (1.7% vs 2.1%), unsatisfactory visual or refractive outcome (1.7% vs. 0.5%), and infection (0% vs. 1.1%), respectively. The 3-year predicted probability of a rejection episode was 9% with DSAEK versus 20% with PKP (P = 0.0005). The median 3-year cell loss for DSAEK and PKP was 46% and 51%, respectively (P = 0.33), in Fuchs'' dystrophy cases and 59% and 61%, respectively (P = 0.70), in the non-Fuchs'' cases. At 3 years, use of a smaller DSAEK insertion incision was associated with significantly higher cell loss (60% vs. 33% for 3.2- and 5.0-mm incisions, respectively; P = 0.0007), but not with a significant difference in graft survival (P = 0.45). Conclusions: The graft success rate and endothelial cell loss were comparable at 3 years for DSAEK and PKP procedures. A 5-mm DSAEK incision width was associated with significantly less cell loss than a 3.2-mm incision. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Fuchs endothelial corneal dystrophy (FECD) is the most common late-onset, vision-threatening corneal dystrophy in the United States, affecting about 4% of the population. Advanced FECD involves a thickening of the cornea from stromal edema and changes in Descemet membrane. To understand the relationship between FECD and central corneal thickness (CCT), we characterized common genetic variation in COL8A2 and TCF4, genes previously implicated in CCT and/or FECD. Other genes previously associated with FECD (PITX2, ZEB1, SLC4A11), and genes only known to affect CCT (COL5A1, FOXO1, AVGR8, ZNF469) were also interrogated. FECD probands, relatives and controls were recruited from 32 clinical sites; a total of 532 cases and 204 controls were genotyped and tested for association of FECD case/control status, a 7-step FECD severity scale and CCT, adjusting for age and sex. Association of FECD grade with TCF4 was highly significant (OR = 6.01 at rs613872; p = 4.8x10-25), and remained significant when adjusted for changes in CCT (OR = 4.84; p = 2.2x10-16). Association of CCT with TCF4 was also significant (p = 6.1x10-7), but was abolished with adjustment for FECD grade (p = 0.92). After adjusting for FECD grade, markers in other genes examined were modestly associated (p ~ 0.001) with FECD and/or CCT. Thus, common variants in TCF4 appear to influence FECD directly, and CCT secondarily via FECD. Additionally, changes in corneal thickness due to the effect of other loci may modify disease severity, age-at-onset, or other biomechanical characteristics. [ABSTRACT FROM AUTHOR]

Purpose: To assess outcomes 1 year after Descemet''s stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor Study. Design: Multicenter, prospective, nonrandomized clinical trial. Participants: A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs'' dystrophy or pseudophakic/aphakic corneal edema) compared with 410 subjects undergoing PKP from the SMAS who had clear grafts with at least 1 postoperative specular image within a 15-month follow-up period. Methods: The DSAEK procedures were performed by 2 experienced surgeons per their individual techniques, using the same donor and similar recipient criteria as for the PKP procedures in the SMAS performed by 68 surgeons at 45 sites, with donors provided from 31 eye banks. Graft success and complications for the DSAEK group were assessed and compared with the SMAS group. Endothelial cell density (ECD) was determined from baseline donor, 6-month (range, 5–7 months), and 12-month (range, 9–15 months) postoperative central endothelial images by the same reading center used in the SMAS. Main Outcome Measures: Endothelial cell density and graft survival at 1 year. Results: Although the DSAEK recipient group criteria were similar to the PKP group, Fuchs'' dystrophy was more prevalent in the DSAEK group (85% vs. 64%) and pseudophakic corneal edema was less prevalent (13% vs. 32%, P<0.001). The regraft rate within 15 months was 2.3% (DSAEK group) and 1.3% (PKP group) (P = 0.50). Percent endothelial cell loss was 34±22% versus 11±20% (6 months) and 38±22% versus 20±23% (12 months) in the DSAEK and PKP groups, respectively (both P<0.001). Preoperative diagnosis affected endothelial cell loss over time; in the PKP group, the subjects with pseudophakic/aphakic corneal edema experienced significantly higher 12-month cell loss than the subjects with Fuchs'' dystrophy (28% vs. 16%, P = 0.01), whereas in the DSAEK group, the 12-month cell loss was comparable for the 2 diagnoses (41% vs. 37%, P = 0.59). Conclusions: One year post-transplantation, overall graft success was comparable for DSAEK and PKP procedures and endothelial cell loss was higher with DSAEK. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Purpose: To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. Design: Multi-center prospective, double-masked, clinical trial. Methods: ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. Results: ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. Conclusions: In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection. [Copyright &y& Elsevier]

Purpose: To describe reliable methods for determining central corneal endothelial cell density (ECD) in a multicenter eye bank study. Methods: The Specular Microscopy Reading Center utilized a dual-grading procedure and adjudication process to classify image quality and determine ECD for a subset of donor endothelial images obtained in the Specular Microscopy Ancillary Study, which is part of the Cornea Donor Study. 1 Two certified readers classified images as analyzable (excellent, good, fair) or unanalyzable and determined the ECD using a variable frame technique. An adjudicator also evaluated the images if quality classifications by the two readers differed by one grade, if any reader found the image unanalyzable, and/or if the ECD determination between the two readers was = 5%. Results: Image quality categorization by the two readers was identical for 441 (64%) of 688 donor images. The ECD differed by [ABSTRACT FROM AUTHOR]

Investigates the role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Account of infections of parasitic filarial nematodes; Use of a murine model for river blindness; Injection of soluble extracts of filarial nematodes into the corneal stroma; Cause of the predominant inflammatory response in the cornea.