Predictors of Receiving Keratoplasty for Fuchs' Endothelial Corneal Dystrophy among Medicare Beneficiaries.

PURPOSE: To identify factors associated with receipt of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) in patients with Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare beneficiaries 65 years of age or older with a FECD diagnosis between 2011 and 2019. METHODS: The 100% Medicare fee-for-service administrative claims database was queried for treatment-naïve FECD patients. A multivariate logistic regression model including age, race and ethnicity, sex, geography, ocular comorbidities and surgeries, Charlson comorbidity index (CCI), and socioeconomic status was used to identify factors associated with receipt of EK and PK. Kaplan-Meier survival analyses were used to determine the rate of EK after cataract or complex or other anterior segment surgery. MAIN OUTCOME MEASURES: Factors associated with receipt of an EK or PK, plus rate of EK after cataract or complex or other anterior segment surgery. RESULTS: Of 719 066 beneficiaries identified, 31 372 (4.4%) received an EK and 2426 (0.3%) received a PK. In a multivariate analysis, female sex decreased likelihood of both EK and PK (adjusted odds ratio 0.83 [95% confidence interval 0.81-0.85] and 0.84 [0.78-0.92], respectively), while Western residence (1.33 [1.29-1.38]; 1.25 [1.11-1.42]) compared to Southern and history of complex or other anterior segment surgery (1.62 [1.54-1.70]; 5.52 [4.97-6.12]) increased the likelihood of both. Compared to Whites, the likelihood of EK was decreased for Black (0.76 [0.72-0.80]), Asian or Pacific Islander (0.54 [0.48-0.61]), and Hispanic or Latino (0.62 [0.55-0.70]) race and ethnicity, while for the same groups likelihood of PK was increased (for Black 1.32 [1.14-1.53]; Asian/Pacific Islander 1.46 [1.13-1.89]; and Hispanic/Latino 1.62 [1.25-2.11]). Following cataract or complex/other anterior segment surgery, rates of EK were 1.3% and 3.3% at 1 year and 2.3% and 5.6% at 8 years, respectively. CONCLUSIONS: In a multivariate analysis, women beneficiaries are less likely to receive EK or PK for FECD compared with men, whereas non-White beneficiaries are less likely to receive EK and more likely to receive PK compared with White beneficiaries.

A Longitudinal Study of Ebola Sequelae in Liberia.

BACKGROUND: Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult. METHODS: We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined. RESULTS: A total of 966 EBOV antibody-positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%), and joint pain (47.5% vs. 17.5%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months. CONCLUSIONS: A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months. (Funded by the National Institute of Allergy and Infectious Diseases and the National Eye Institute; PREVAIL III ClinicalTrials.gov number, NCT02431923.).

Peripheral-to-central ratio of Guttae: validity and reliability of an objective method to characterize severity of Fuchs endothelial corneal dystrophy.

PURPOSE: Common methods of measuring severity of Fuchs endothelial corneal dystrophy (FECD) are limited in objectivity, reliability, or start with a variable baseline that prevents distinguishing healthy from affected eyes. The aim of this study was to describe a method of grading FECD that overcomes these limitations. METHODS: Fifteen patients with Fuchs endothelial corneal dystrophy were included in the study. Guttae were imaged with a slit lamp beam 8 mm tall; the bottom 4 mm half of each image was divided into two equally-sized sections. Guttae were counted by four independent graders blinded to disease severity scores. The peripheral:central guttae ratio was compared to modified Krachmer clinical severity scores. The peripheral:central guttae ratio was compared between mild (severity 0.5-3) versus moderate-to-severe (severity 4-5) disease. Receiver operating characteristics defined optimal ratio cutoffs for mild versus moderate-to-severe disease. RESULTS: Increased peripheral guttae and peripheral:central guttae ratio correlated with Krachmer severity (p = 0.021 and p = 0.009, respectively). The difference between mild and moderate-to-severe cases for the peripheral:central guttae ratio was significant (p < 0.001). Inter-rater reliability of total guttae count was high (coefficient = 0.82, p < 0.001). A peripheral:central guttae ratio of 0.16 was the ideal cut-off point (area under the curve = 0.79, sensitivity = 0.78, and specificity = 0.80). CONCLUSION: In this pilot study, the peripheral:central ratio of guttae correlates with subjective clinical severity of Fuchs dystrophy. It starts at a common baseline, has good inter-rater reliability, does not require dilation, and can be conducted with a smartphone and slit-lamp.

Bilateral EK Rejection After COVID-19 Vaccine.

ABSTRACT: Owing to its rapid development, short-term and long-term effects of the COVID-19 vaccine are still not well understood. This case report highlights bilateral corneal endothelial graft rejection after administration of the Pfizer COVID-19 vaccine. A 73-year-old woman with bilateral Descemet stripping endothelial keratoplasty presented with bilateral decreased visual acuity, ocular pain, and photophobia after her second dose of the Pfizer-BioNTech COVID-19 vaccine. Two weeks after vaccine administration, the uncorrected visual acuity was 20/70 and 20/40. Central corneal thickness as measured by ultrasound was 809 and 825 µm and by Scheimfplug imaging was 788 and 751 µm at the pupil center. Slit-lamp biomicroscopy revealed quiet conjunctiva and sclera but was significant for thickened corneas with Descemet folds in both eyes. The patient was instructed to use prednisolone acetate 1% every 1 to 2 hours with Muro ointment at bedtime.

Testing a Popular Smartphone Application for Colour Vision Assessment in Healthy Volunteer Subjects.

We aimed to compare the Ishihara pseudoisochromatic colour vision test with a colour vision test from a popular smartphone application (EyeHandBook [EHB]) using digital image processing to simulate colour vision deficiencies. Three digital versions of the Ishihara and EHB slides were created: full colour; 32 bit- greyscale (removing all colour information); and blue channel (to simulate red-green colour vision deficiencies). Twenty healthy volunteers were shown each colour-edited plate. The answers they reported were compared with what would be expected for that colour-simulation scenario based on the answer key provided in the Ishihara booklet ("expected" answer). There were nine plates that had comparable patterns between the EHB and Ishihara test. We found no significant difference in the overall proportion of "expected" answers for the full colour (p = .35), 32 bit-greyscale (p = .39) and blue channel (p = .22) conditions. There were significant differences between the proportion of "expected" answers among six individual colour- edited plates (p < .05 for each). Colour vision assessment from the EHB is distinct from comparable Ishihara plates. Clinical scenarios that require serial assessment of colour vision may benefit from using the same modality consistently rather than exchanging between the two tests with the assumption of equivalence. Refinement of digital colour editing techniques beyond 32-bit greyscale and RGB channel splitting is necessary in order to accurately simulate colour vision deficiency.

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

OBJECTIVES: To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. METHODS: Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. RESULTS: Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3). CONCLUSION: Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Prognostic factors and survival for malignant conjunctival melanoma and squamous cell carcinoma over four decades.

PURPOSE: To determine the epidemiology and survival of primary conjunctival malignant neoplasms. METHODS: Retrospective analysis of primary malignant conjunctival neoplasms using Surveillance, Epidemiology, and End Results database from 1973 to 2012. RESULTS: Of 1661 cases, the most common neoplasms are squamous cell carcinoma (SCC) at 54.8% and melanoma at 38.8%. Mean diagnostic age for melanoma was 62.1 compared to 65.5 years for SCC (p = 0.002). 52.2% of melanoma are male versus 77.4% of SCC (p < 0.001). For SCC only age (HR: 1.09, 95% CI:1.04-1.14) is a predictor of survival. For melanoma, age (HR: 1.07, 95% CI: 1.05-1.10), male sex (HR: 2.04, 95% CI: 1.16-3.60), T4 tumors (HR: 3.38, 95% CI: 1.17-9.80) and N1 status (HR: 8.69, 95% CI: 2.75-27.42) are all survival predictors. The 5 and 10-year overall survival (OS) estimates are not significantly different between SCC and melanoma, with 70% and 50% respectively for SCC, and 71% and 50% respectively for melanoma. Median survival time is worse for blacks (52 months) compared to whites (118 months) and Asians/Native Americans/Pacific Islanders (145 months), however race was not found to be a significant prognostic factor in multivariate analysis. Five-year survival are similar between decades 1973-1982 (66.2%), 1983-1992 (69.2%), 1993-2002 (71.3%) and 2003-2012 (70.2%). CONCLUSION: Age at diagnosis is a determinant of survival for both conjunctival SCC and melanoma. Male sex, T4 and N1 staging are also important prognostic factors for melanoma. With respect to overall survival, SCC and melanoma did not differ significantly.

Endothelial keratoplasty for corneal endothelial dystrophy in a dog.

OBJECTIVE: To assess the efficacy of an endothelial keratoplasty procedure at defined intervals to 1 year postoperatively for the treatment of corneal endothelial dystrophy (CED) in a canine patient. PROCEDURE: A dog diagnosed with CED with progressive corneal edema underwent an endothelial keratoplasty. The patient was examined pre- and postoperatively with slit lamp biomicroscopy and ultrasonic pachymetry. RESULTS: Mean central corneal thickness (CCT) measured with pachymetry was >1400 µm preoperatively and decreased postoperatively to 725 µm. The transplanted donor tissue became transparent 2 weeks postoperatively and incorporated with the recipient cornea. The graft remained transparent throughout the duration of the postoperative period evaluated in this study (2 weeks postoperatively to 1 year). The canine patient was comfortable pre- and postoperatively. CONCLUSIONS: Endothelial keratoplasty is a potential therapeutic option for canine cases with progressive corneal thickening due to CED. As this is a single case study, further investigation into the use of endothelial keratoplasty to treat CED is warranted. Moreover, canine patients with CED might serve as a surgical model for human patients with Fuchs' Endothelial Corneal Dystrophy.

Comparison of a Smartphone Application with Ishihara Pseudoisochromatic Plate for Testing Colour Vision.

The Eye Handbook (EHB) is the most frequently downloaded smartphone application with diagnostic tools for eye-care providers. However, limited data exists validating the EHB test to gold standard colour vision testing. EHB and Ishihara colour vision tests were evaluated and compared under simulated colour vision loss through use of image processing software. Images of both tests were processed through ImageJ to 32 bit-grey scale and blue channel under split RBG channel to model total colour vision loss and red-green (R-G) deficiency, respectively. Two colour plates differentiated R-G deficiency from total colour blindness in EHB compared with eight Ishihara plates. Without colour information, correct numerals were identified in 3.5/15 EHB plates converted to 32-bit greyscale, versus 1/16 in Ishihara. We conclude EHB may underestimate colour vision loss severity in persons with normal contrast sensitivity compared to Ishihara. Eye-care providers need to be aware of the potential inconsistency compared to standardised methods, including limitations in differentiating patients with R-G colour deficiencies from total colour blindness.

Effects of Contrast Sensitivity on Colour Vision Testing.

This study analyses how contrast sensitivity loss affects colour vision (CV) testing. Eleven participants were scored while cycling through randomly arranged pictures of CV tests with varying levels of contrast changes applied. Hardy-Rand-Rittler (HRR) scores declined significantly at each successive decrease in contrast level after the highest setting (p < 0.004). HRR scores were also lower than those for Ishihara and Farnsworth D-15 tests at two contrast settings (p < 0.01). Contrast changes had the greatest impact on HRR scores, indicating that this test may not be an accurate reflection of CV in patients with contrast sensitivity loss.

First Human Case of Fungal Keratitis Caused by a Putatively Novel Species of Lophotrichus.

We report an aggressive fungal keratitis caused by a putatively novel species of Lophotrichus in a patient with traumatic injury to the cornea from a dog paw. The organism was isolated from the patient's necrotic cornea, which perforated despite coverage with hourly fortified broad-spectrum topical antibiotic therapy. This report represents the first case of human infection caused by this species.

Fluorescein-conjugated hyaluronic acid enables visualization of retained ophthalmic viscosurgical device in anterior chamber.

PURPOSE: To develop and assess the utility of ophthalmic viscosurgical device (OVD) manufactured with fluorescein-conjugated hyaluronic acid (conjHA). SETTING: Department of Biomedical Engineering and the Wilmer Eye Institute, Johns Hopkins University and School of Medicine, Baltimore, MD, USA. DESIGN: Laboratory study. METHODS: ConjHA and unconjugated HA (unconjHA) at varied ratios were used to produce OVD (conjOVD) with varied fluorescence intensity. The conjHA:unconjHA ratio was optimized to maximize clarity under white light and fluorescence intensity under cobalt blue light (CBL), allowing for conditional visualization. The effect of conjugation on conjOVD viscosity was assessed via rotational rheometry. Intraocular lenses (IOLs) were immersed in conjOVD for 4 hours to assess staining of IOLs. A proof-of-concept study was performed in ex vivo porcine eyes. Following injection and visualization, the OVDs were removed from the eyes via irrigation/aspiration (I/A). RESULTS: 0.5 mg/mL of conjHA (degree of substitution=0.005) enabled robust fluorescence of conjOVD under CBL. Fluorescein-conjugation did not significantly affect conjOVD viscosity (P>0.05 for mean difference in viscosity at all shear rates tested). No staining of IOLs was appreciated. ConjOVD was visualized under CBL when injected ex vivo and maintained clarity of the anterior chamber under white light. Importantly, conjHA enabled delineation of retained OVD following I/A. CONCLUSIONS: Use of OVD composed of fluorescein-conjugated HA is a feasible method to enable conditional visualization of OVD intraoperatively without nonspecific staining of ocular structures. Further development of this technology may enable accelerated OVD removal in ocular surgery or decreased OVD retention following surgery.

Tandem Mass Tag LC-MS/MS of Aqueous Humor From Individuals With Type 2 Diabetes Without Retinopathy Reveals Early Dysregulation of Synaptic Proteins.

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR. Methods: Aqueous fluid was collected from subjects with type 2 diabetes mellitus (DM) but no clinical DR and from nondiabetic controls undergoing routine cataract surgery. Preoperative spectral-domain optical coherence tomography of the macula was obtained. Tandem mass tag LC-MS/MS was performed to identify proteins differentially present in diabetic and control aqueous fluid, and proteins with >50% change and P < 0.05 were considered significant. Selected results were validated with western blot of human aqueous fluid samples. Results: We identified decreased levels of proteins implicated in neuronal synapse formation and increased levels of inflammatory proteins in the aqueous fluid from patients with type 2 DM but no DR compared with controls. Of the differentially present synaptic proteins that we identified and confirmed with western blot, the majority have not previously been linked with DRD. Conclusions: The proteomic profile of aqueous fluid from individuals with type 2 DM but no DR suggests that retinal neuronal dysfunction and inflammation represent very early events in the pathophysiology of DRD. These findings support the concept that diabetic retinal neurodegeneration precedes vascular pathology and reveal novel potential mediators and/or biomarkers warranting further investigation.

Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact with FCD4 on chromosome 9p.

Fuchs corneal dystrophy (FCD) is a degenerative genetic disorder of the corneal endothelium that represents one of the most common causes of corneal transplantation in the United States. Despite its high prevalence (4% over the age of 40), the underlying genetic basis of FCD is largely unknown. Here we report missense mutations in TCF8, a transcription factor whose haploinsufficiency causes posterior polymorphous corneal dystrophy (PPCD), in a cohort of late-onset FCD patients. In contrast to PPCD-causing mutations, all of which are null, FCD-associated mutations encode rare missense changes suggested to cause loss of function by an in vivo complementation assay. Importantly, segregation of a recurring p.Q840P mutation in a large, multigenerational FCD pedigree showed this allele to be sufficient but not necessary for pathogenesis. Execution of a genome-wide scan conditioned for the presence of the 840P allele identified an additional late-onset FCD locus on chromosome 9p, whereas haplotype analysis indicated that the presence of the TCF8 allele and the disease haplotype on 9p leads to a severe FCD manifestation with poor prognosis. Our data suggest that PPCD and FCD are allelic variants of the same disease continuum and that genetic interaction between genes that cause corneal dystrophies can modulate the expressivity of the phenotype.

Intraglandular injection of botulinum toxin a reduces tear production in rabbits.

PURPOSE: To develop an animal model and investigate the dose-dependent effect of an intraglandular injection of botulinum toxin A (BTX-A) on tear production. METHODS: In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected transconjunctivally in the superolateral lobe of the lacrimal gland of adult New Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9% sodium chloride was injected. Prior to injection and at 1-week postinjection, photographs were taken to evaluate pre- and postoperative eyelid position. Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and Schirmer test was used to assess tear production. RESULTS: Glands injected with the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a statistically significant decrease in tear production (p = 0.002 and 0.007, respectively) compared with the contralateral saline-injected glands at 1 week. No corneal pathologic factors from excessive dryness were observed following the injection. While postinjection ptosis was observed (p = 0.025), no difference was seen between BTX-A and saline-injected eyes. CONCLUSIONS: In rabbits, intraglandular injection of BTX-A resulted in decreased tear production at 1 week. No additional reduction in tear production was seen with a BTX-A dose greater than 1.25 U, suggesting glandular receptor saturation at this dose. Despite suppression of tear production, no corneal pathologic factors were observed. Further studies are needed to refine this animal model with the ultimate goal of determining optimum delivery route and concentration to reduction in tear production while minimizing side effects in patients.

Sutured Descemet Membrane Endothelial Keratoplasty in Patients With Complex Anatomy or Difficulty Positioning.

PURPOSE: In Descemet membrane endothelial keratoplasty (DMEK), some patients cannot adhere to postoperative positioning requirements or lack anatomic support for a gas bubble in the anterior chamber. We describe a suturing technique that stabilizes the graft postoperatively without tearing or tenting it. METHODS: One to two 10-0 nylon sutures with a spatulated needle are used to secure DMEK grafts. Tied with minimal tension, the sutures traverse the corneal stroma at a steep, almost perpendicular angle and approach the graft from the limbus at an angle tangential to the circular graft to prevent vaulting the tissue off the central cornea. We report preoperative and postoperative best spectacle-corrected visual acuity, corneal pachymetry, and anterior segment optical coherence tomography confirming graft attachment in 3 patients. RESULTS: In case 1 (aphakia, postvitrectomy, and positioning difficulty), pachymetry decreased from 637 µm preoperatively to 495 µm and best spectacle-corrected visual acuity improved from 20/70 to 20/50 at postoperative week 1. In case 2 (aphakia, limited follow-up, and medication adherence), pachymetry decreased from 1106 µm preoperatively to 783 µm at postoperative month 1. In case 3 (tube shunt and loss of gas bubble at 2 hours), slit-lamp examination at postoperative day 1 showed corneal clearing and graft attachment. Pachymetry decreased from over 795 µm preoperatively to 582 µm at postoperative month 1. Anterior segment optical coherence tomography confirmed graft attachment in all patients. CONCLUSIONS: Single or opposing tangentially oriented sutures can be safely applied to secure DMEK grafts postoperatively in challenging cases.

Mobile-CellNet: Automatic Segmentation of Corneal Endothelium Using an Efficient Hybrid Deep Learning Model.

PURPOSE: The corneal endothelium, the innermost layer of the human cornea, exhibits a morphology of predominantly hexagonal cells. These endothelial cells are believed to have limited regeneration capacity, and their density decreases over time. Endothelial cell density (ECD) can therefore be used to measure the health of the corneal endothelium and the overall cornea. In clinical settings, specular microscopes are used to image this layer. Owing to the unavailability of reliable automatic tools, technicians often manually mark the cell centers and borders to measure ECD for such images, a process that is time and resource-consuming. METHODS: In this article, we propose Mobile-CellNet, a novel completely automatic, efficient deep learning-based cell segmentation algorithm to estimate ECD. This uses 2 similar image segmentation models working in parallel along with image postprocessing using classical image processing techniques. We also compare the proposed algorithm with widely used biomedical image segmentation networks U-Net and U-Net++. RESULTS: The proposed technique achieved a mean absolute error of 4.06% for the ECD on the test set, comparable with the error for U-Net of 3.80% ( P = 0.185 for difference), but requiring almost 31 times fewer floating-point operations (FLOPs) and 34 times fewer parameters. CONCLUSIONS: Mobile-CellNet accurately segments corneal endothelial cells and reports ECD and cell morphology efficiently. This can be used to develop tools to analyze specular corneal endothelial images in remote settings.

Alcohol Abuse Is Associated With Alterations in Corneal Endothelial Cell Morphology.

PURPOSE: Alcohol consumption is highly prevalent throughout the world. We sought to detect, in a large sample of cornea donors, whether alcohol abuse is associated with changes in corneal endothelial morphology after accounting for other comorbidities including tobacco use. METHODS: At a single eye bank, 10,322 eyes from a total of 5624 unique donors underwent imaging with a Konan CellChek D specular microscope. Demographic information and medical history were associated with each tissue. Images were analyzed using a standardized protocol for assessment of endothelial cell density, hexagonality, and variation. In this retrospective analysis, a multivariable regression was conducted to assess for an association between alcohol abuse and corneal endothelial metrics. Measurements were averaged across eyes for each donor. Bonferroni corrections were applied to account for multiple comparisons. RESULTS: Among 5624 donors, the mean (standard deviation) endothelial cell density was 2785 (383.0) cells/mm 2 . Indicators of alcohol abuse were present in 1382 donors (24.5%). In a multivariable regression model that included age, sex, tobacco use, history of cataract surgery, and diabetes mellitus, alcohol abuse was associated with a decrease of 60.9 cells/mm 2 [95% confidence interval (CI), -83.0 to -38.7 cells/mm 2 , P = 7.6 × 10 -8 ], an increase in the coefficient of variation by 0.0048 (95% CI, 0.17-0.79, P = 0.002), and a decrease in percent hexagonality by 0.93% (95% CI, -1.3 to -0.6, P = 4.5 × 10 -7 ). CONCLUSIONS: Alcohol abuse is associated with significant alterations to corneal endothelial density and morphology.

Comparison of corneal endothelial cell density and morphology with Optisol GS and Life4C storage media in the eye bank: a 5-year retrospective analysis.

Purpose: Optisol GS and Life4C are corneal storage media used by eye banks worldwide. We sought to determine if either solution was associated with superior corneal endothelial cell density (ECD) or morphology in a large cohort of donor corneas. Methods: From January 2016 through December 2020, 10,316 corneas from 5,624 unique donors were acquired and analyzed at Rocky Mountain Lions Eye Bank. In April 2019, Life4C replaced Optisol GS as the sole storage medium. We compared ECD and morphology before and after April 2019, and excluded corneas processed within the transition period. Univariable and multivariable regression analyses accounted for age, sex, tobacco use, heavy alcohol use, and diabetes. Only right corneas were analyzed to account for the correlation between eyes. Results: Of 5042 right corneas analyzed, 3486 were stored in Optisol GS and 1556 in Life4C. There was no significant difference in ECD across groups (2794 vs. 2793 cells/mm2 in Optisol GS and Life4C, p=0.88). In multivariate analyses, there was no significant difference in corneal ECD (0.6 cells/mm2 higher with Life4C, p=0.96) or hexagonality (0.22% higher with Life4C, p=0.31). However, the coefficient of variation was significantly lower in the Life4C group (-0.0039, p=0.03). After adjustment for above factors, corneas in Life4C demonstrated a 3.1% decreased likelihood of exhibiting CV values greater than 0.40 (p=0.009). Conclusions: This study demonstrates comparable and favorable outcomes using both storage media and confirms their overall efficacy. The decreased CV in Life4C is not of clinically significant magnitude, but merits further research in clinical and long-term settings.

Clinical trial data sharing: a cross-sectional study of outcomes associated with two U.S. National Institutes of Health models.

The impact and effectiveness of clinical trial data sharing initiatives may differ depending on the data sharing model used. We characterized outcomes associated with models previously used by the U.S. National Institutes of Health (NIH): National Heart, Lung, and Blood Institute's (NHLBI) centralized model and National Cancer Institute's (NCI) decentralized model. We identified trials completed in 2010-2013 that met NIH data sharing criteria and matched studies based on cost and/or size, determining whether trial data were shared, and for those that were, the frequency of secondary internal publications (authored by at least one author from the original research team) and shared data publications (authored by a team external to the original research team). We matched 77 NHLBI-funded trials to 77 NCI-funded trials; among these, 20 NHLBI-sponsored trials (26%) and 4 NCI-sponsored trials (5%) shared data (OR 6.4, 95% CI: 2.1, 19.8). From the 4 NCI-sponsored trials sharing data, we identified 65 secondary internal and 2 shared data publications. From the 20 NHLBI-sponsored trials sharing data, we identified 188 secondary internal and 53 shared data publications. The NHLBI's centralized data sharing model was associated with more trials sharing data and more shared data publications when compared with the NCI's decentralized model.