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.

Effect of Anterior Chamber Air on Central Corneal Thickness in Human Donor Eyes.

PURPOSE: The purpose of this study was to describe the effects of intracameral air on corneal edema. METHODS: A laboratory investigation was performed on human donor corneas. Baseline pachymetry measurements through anterior segment optical coherence tomography and endothelial cell density were obtained for all corneas. Each pair of corneas was separated and randomly assigned to undergo air injection or Optisol-GS into a BIONIKO artificial anterior chamber for 5 minutes at physiologic intraocular pressure confirmed by digital palpation. Photographs were obtained immediately on connection of the cornea to the artificial anterior chamber and on completion of the 5 minutes of treatment, with anterior chamber air being exchanged for Optisol-GS. Pretreatment and posttreatment photographs were obtained. Immediately after treatment, pachymetry was again obtained on all corneas. Pachymetry data underwent statistical analysis. RESULTS: Corneal pachymetry improved from 690.5 ± 126.6 to 576.1 ± 87.2 µm, yielding a 114.4 ± 50.4 µm improvement of pachymetry in the group with air injected into the anterior chamber. This was a significant improvement of pachymetry when compared with the group with Optisol-GS injected into the anterior chamber, which showed an improvement from 662.3 ± 126.5 to 613.5 ± 108.0 µm, yielding an improvement of 48.8 ± 34.3 µm. CONCLUSIONS: Injection of air into the anterior chamber leads to a significant decrease in corneal pachymetry. We thereby propose that injecting air intracamerally is an effective intraoperative intervention when visualization is negatively affected by corneal edema.

Canine Descemet Stripping Endothelial Keratoplasty with a Tissue Insertion Device: Technique and Long-Term Outcome.

Introduction. We describe a case of canine Descemet's stripping endothelial keratoplasty (DSEK) using an open-source canine tissue delivery device. Case Presentation. We follow the four-year outcomes of a 1.5-year-old Tibetan Terrier who presented with difficulty seeing, diffuse corneal edema, and central corneal thickness of 1400 microns in the left eye. To perform DSEK, a polycarbonate carrier and insertion device was designed for canine corneas that measure up to 15 mm in diameter. The tissue was loaded into the inserter prior to surgery with the endothelium facing inwards and the stroma facing the cartridge wall. From the cartridge, the graft was pulled into the eye using microforceps and an anterior chamber maintainer. We assessed preoperative endothelial cell count, postoperative corneal clearance, and graft adhesion. The donor was a two-year-old Airedale Terrier who died one day prior to surgery, with endothelial cell density of 3149 cells/mm2. One week after DSEK, the cornea began to clear, and pachymetry of the donor and graft total was 1410 microns. This improved to 800 microns at 4 months and continued improving in its clarity at the last postoperative visit 4 years after surgery. Discussion. We demonstrate the feasibility of conducting canine endothelial keratoplasty with a specially designed tissue delivery device and the potential of long-term corneal clearance after DSEK in canine eyes.

Quality and Agreement With Scientific Consensus of ChatGPT Information Regarding Corneal Transplantation and Fuchs Dystrophy.

PURPOSE: ChatGPT is a commonly used source of information by patients and clinicians. However, it can be prone to error and requires validation. We sought to assess the quality and accuracy of information regarding corneal transplantation and Fuchs dystrophy from 2 iterations of ChatGPT, and whether its answers improve over time. METHODS: A total of 10 corneal specialists collaborated to assess responses of the algorithm to 10 commonly asked questions related to endothelial keratoplasty and Fuchs dystrophy. These questions were asked from both ChatGPT-3.5 and its newer generation, GPT-4. Assessments tested quality, safety, accuracy, and bias of information. Chi-squared, Fisher exact tests, and regression analyses were conducted. RESULTS: We analyzed 180 valid responses. On a 1 (A+) to 5 (F) scale, the average score given by all specialists across questions was 2.5 for ChatGPT-3.5 and 1.4 for GPT-4, a significant improvement (P < 0.0001). Most responses by both ChatGPT-3.5 (61%) and GPT-4 (89%) used correct facts, a proportion that significantly improved across iterations (P < 0.00001). Approximately a third (35%) of responses from ChatGPT-3.5 were considered against the scientific consensus, a notable rate of error that decreased to only 5% of answers from GPT-4 (P < 0.00001). CONCLUSIONS: The quality of responses in ChatGPT significantly improved between versions 3.5 and 4, and the odds of providing information against the scientific consensus decreased. However, the technology is still capable of producing inaccurate statements. Corneal specialists are uniquely positioned to assist users to discern the veracity and application of such information.

Intraocular Lens Unfurling Time Exponentially Decays with Increased Solution Temperature.

Purpose: Intraocular lens (IOL) unfurling can be a rate-limiting step in cataract surgery, limiting operative efficiency. Furthermore, inefficient unfurling has important implications for clinical outcomes. We examine the effects of solution temperature on IOL unfurling time using three in vitro models of the ocular environment. Methods: IOLs were injected into a 6-well plate filled with balanced salt solution (BSS), dispersive ophthalmic viscoelastic device (OVD), or cohesive OVD. Experiments were also performed in a plastic eye filled with dispersive or cohesive OVD. IOL unfurling time was recorded against the temperature of the respective solution. Results: IOL unfurling time decayed exponentially as solution temperature increased in all experiments, including the BSS-filled 6-well plate, the OVD-filled 6-well plate, and the OVD-filled plastic eye. IOLs failed to unfurl within 10 min at 10°C, below the glass transition temperature of the tested IOLs. Increasing solution temperature from 20°C to 30°C decreases IOL unfurling by greater than 2 min. Further heating to 40°C did not significantly decrease IOL unfurling time. Conclusion: Increased solution temperature rapidly decreases IOL unfurling time in vitro. IOLs do not unfurl within a clinically acceptable timeframe at or below their glass transition temperature. Increased BSS and/or OVD temperature may be a potential method to decrease IOL unfurling time in cataract surgery. However, future research is needed to elucidate potential consequences of warmed BSS and/or OVD on post-operative outcomes. This study demonstrates the potential for temperature regulation to decrease cataract surgery operative time and provides preliminary evidence to justify future clinical validation of this relationship.

During cataract surgery, a prosthetic intraocular lens (IOL) is inserted into the eye once the clouded lens is removed. The IOL must then unfurl before the procedure can proceed. When IOLs fail to unfurl or unfurl slowly, this can delay the operation and may even cause post-operative complications. Thus, we studied the effect temperature may have on IOL unfurling time to optimize this segment of the operation. We injected IOLs into solutions of saline (balanced salt solution) or ophthalmic viscoelastic device (OVD), two fluids injected into the eye during surgery. In both a well plate and a plastic eye, we found that increasing the temperature of the solution significantly affected IOL unfurling time. Specifically, heating the solution from refrigeration to room temperature decreased unfurling time from over 10 min to less than four. Heating to physiological temperature further decreased unfurling time to less than a minute. Our results show promise for potentially utilizing heated BSS and/or OVD to accelerate IOL unfurling and decrease cataract surgery operative time.

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.

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.

Long-Term Decrease in Intraocular Pressure in Survivors of Ebola Virus Disease in the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Study.

Objective: Survivors of Ebola virus disease (EVD) experience decreased intraocular pressure (IOP) relative to unaffected close contacts during the first year of convalescence. Whether this effect persists over time and its relationship to intraocular pathology are unclear. We sought to determine whether IOP remained lower in survivors of EVD over 4 years of follow-up and to identify associated risk factors. Design: Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III is a 5-year, longitudinal cohort study of survivors of EVD and their close contacts and is a collaboration between the Liberian Ministry of Health and the United States National Institutes of Health. Participants: Participants who enrolled in PREVAIL III at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 who underwent comprehensive ophthalmic evaluation annually for 5 consecutive visits. Methods: Intraocular pressure was measured at each visit by a handheld rebound tonometer using sterile tips. Comparisons are made between antibody-positive survivors and antibody-negative close contacts. Main Outcome Measures: Intraocular pressure, measured in mmHg, at each study visit. Results: Of 565 antibody-positive survivors and 644 antibody-negative close contacts enrolled in the study at baseline, the majority of participants returned annually, with 383 (67.8%) and 407 (63.2%) participants, respectively, presenting for the final study visit at a median of 60 months after symptom onset. A sustained, relative decrease in IOP was observed in survivors relative to close contacts, with mean difference of -0.72 mmHg (95% confidence interval [CI] -1.18 to -0.27) at the final study visit. This difference remained constant throughout the study period (P = 0.4 for interaction over time). Among survivors, physical examination findings of vitreous cell and OCT findings of vitreous opacities both demonstrated a significant association with decreased IOP at baseline (P < 0.05 for both). After adjusting for such factors, the difference throughout the follow-up (-0.93 mmHg, 95% CI, -1.23 to -0.63) remained significant. Conclusions: Survivors of EVD experienced a sustained decrease in IOP relative to close contacts over a 5-year period after EVD. The results highlight the importance of considering long-term sequelae of emerging infectious diseases within a population. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

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.

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.

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.

Descemet membrane endothelial keratoplasty in eyes with COL8A2-associated corneal dystrophy.

Purpose: The p.(Leu450Trp) COL8A2 mutation, associated with an early-onset corneal endothelial dystrophy, can result in bullous keratopathy within the first few decades of life. People with this condition frequently experience anterior corneal changes in keratometry as the disease worsens, which may potentially affect refractive error after endothelial keratoplasty. We describe outcomes of the first cases of Descemet Membrane Endothelial Keratoplasty (DMEK) for patients with known mutations in this gene. Observations: Four eyes from two patients with COL8A2-associated corneal dystrophy underwent DMEK for this condition at a tertiary academic center. Preoperative and postoperative Scheimpflug imaging and manifest refraction was conducted. Mean central corneal thickness decreased from 713 µm preoperatively to 529 µm at one month. Despite long-standing corneal haze, all eyes reached between 20/20 and 20/30 best corrected visual acuity, and minimum postoperative central corneal thickness reached 482, 479, 479 and 533 µm. Refractive changes frequently occurred during the first postoperative year, with 3.6 D, 3.3 D, 3 D, and 0.8 D shifts in spherical equivalent taking place within this time period in the four eyes. Conclusions and Importance: In two patients with the p.(Leu450Trp) mutation in COL8A2 who underwent DMEK, resolution of corneal edema resulted in centrally thin corneas and refractive shifts postoperatively. Despite chronic edema, excellent visual acuity was achieved in all eyes.

Outcomes of Femtosecond Laser-Assisted Cataract Surgery Compared to Conventional Phacoemulsification in Eyes with Pseudoexfoliation Syndrome.

OBJECTIVE: To compare the outcomes including complications, in a large cohort of eyes with pseudoexfoliation syndrome that underwent Femtosecond Laser-Assisted Cataract Surgery (FLACS) versus conventional phacoemulsification. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 513 eyes from 366 patients with pseudoexfoliation syndrome that underwent cataract surgery between April 1, 2014, and December 31, 2018. METHODS: Charts were reviewed for preoperative examination findings, intraoperative complications, and post-operative outcomes. Best-corrected visual acuity (BCVA) was measured by logMAR and compared between groups at one month and the final follow-up visit. RESULTS: Of 513 eyes, 71 (13.8%) underwent FLACS, and 442 (86.2%) eyes underwent conventional cataract surgery. Between the two groups, there was no difference in the incidence of vitreous prolapse, capsular tear, pupillary expansion device usage, capsular tension support device usage, or postoperative cystoid macular edema (p > .05 for all). At the final visit, there was no significant difference in BCVA between FLACS and conventional phacoemulsification groups (mean logMAR 0.26 vs. 0.25, p = .87). CONCLUSIONS: When comparing FLACS and conventional phacoemulsification in eyes with pseudoexfoliation syndrome, no difference was seen in the incidence of complications. BCVA was comparable between the two groups. Zonular weakness significantly increased the risk of complications in both groups.

Scheimpflug Corneal Densitometry Values and Severity of Guttae in Relation to Visual Acuity in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The purpose of this study was to investigate the association between corneal densitometry (CD) values from Scheimpflug tomography imaging, severity of guttae, and visual acuity in eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS: This was a retrospective, cross-sectional study. Patients with FECD were examined at the Bascom Palmer Eye Institute from January 2015 to September 2019. We extracted CD values at central annuli of 0-2, 2-6, 6-10 and 10-12 mm from Scheimpflug tomography images. We investigated the association of corrected distance visual acuity (CDVA) with CD values, severity of guttae, central corneal thickness (CCT), cataract grade, refractive error, corneal edema grade, age, and gender using multivariate generalized estimating equation regression models. RESULTS: One hundred ninety-two eyes from 110 patients were included in this study. Increase in central CD values at the 0 to 2 mm zone (P < 0.001), severity of guttae (P = 0.046), age (P < 0.001), cataract grade (P < 0.001), corneal edema grade (P < 0.001), and type of refractive error (P = 0.008) were significantly associated with decreased CDVA. Central corneal thickness, sex, and the peripheral CD values (2-6, 6-10, and 10-12 mm) were not significantly associated with CDVA (P > 0.05) in the final multivariate regression model. CONCLUSIONS: Our study demonstrates that central CD values at 0 to 2 mm and severity of guttae are each associated with decreased CDVA in FECD. These findings carry implications for patients with FECD considering surgical intervention for phacoemulsification alone, Descemet stripping only, or endothelial cell transplantation and provide a multifactorial perspective on vision loss in FECD.

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.

Viability of preloaded Descemet membrane endothelial keratoplasty grafts with 96-hour shipment.

OBJECTIVE: To assess feasibility and compare the effects of 96-hour shipment of Descemet membrane endothelial keratoplasty (DMEK) grafts as a scroll or a tri-fold on cell viability. METHODS AND ANALYSIS: DMEK grafts were prepared at the Rocky Mountain Lions Eye Bank. Twenty pre-stripped DMEK grafts, paired from 10 donors, were either tri-folded in an endothelium-in configuration using microforceps and loaded into a plastic Treyetech cartridge, or suctioned in a scrolled endothelium-out configuration into a modified Jones Tube. Grafts were shipped via FedEx to a secondary location and back for 48 hours each way, resulting in a total shipping time of 96 hours. After shipping, grafts were removed from inserters onto glass slides and unfolded using viscoelastic with endothelium facing upwards. Calcein-AM stained grafts were imaged with a fluorescent microscope and endothelial cell loss (ECL) was measured using trainable segmentation in Fiji by a masked grader. RESULTS: A total of 20 grafts were shipped for 96 hours, split between preloaded tri-folded (n=10) and preloaded scrolled (n=10) tissues. No significant difference in ECL was observed across groups after prolonged shipping (14.8% vs 13.7% ECL respectively, p=0.68). CONCLUSION: For preloaded DMEK after 96 hours, both scrolled and tri-folded tissue demonstrated clinically acceptable levels of ECL. The data suggest a wider window of time for endothelial cell viability and is promising for the prospect of international shipment of preloaded grafts.

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.

Presence of SARS-CoV-2 Viral RNA in Aqueous Humor of Asymptomatic Individuals.

PURPOSE: The purpose of this study was to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detectable in the aqueous of asymptomatic individuals presenting for ophthalmic surgery. DESIGN: Prospective cross-sectional study. METHODS: Setting and participants: all patients undergoing anterior segment surgery at an ambulatory surgical center (ASC) belonging to a tertiary academic center in South Florida during a 102-day period between June and September 2020 received nasal swab testing for SARS-CoV-2 and underwent a relevant review of symptoms prior to surgery, with negative results required for both in order to proceed with surgery. Main outcomes and measurements: a small sample of aqueous humor (approximately 0.2 cc) was acquired at the beginning of anterior segment surgery from all participants. Aqueous humor was analyzed for SARS-CoV-2 viral ribonucleic acid (RNA) using real-time reverse transcriptase polymerase chain reaction. Demographic information was acquired from participants for secondary analyses. RESULTS: A total of 70 samples were acquired. Of those, 39 samples were excluded due to insufficient material or inconclusive results. Of 31 samples that were successfully analyzed, 6 (19.4%) demonstrated detectable SARS-CoV-2 RNA. None of the 6 individuals (0%) with detectable viral RNA in aqueous humor reported symptoms during the year, compared to 2 of 25 individuals (8%) with negative samples (P = 1). Positive samples were distributed throughout the study period, including both the first and the last days of enrollment. CONCLUSIONS: The presence of SARS-CoV-2 viral RNA in aqueous despite negative nasal swab testing confirmed its presence beyond the blood-ocular barrier in asymptomatic individuals and raises the possibility that the virus may persist in immunoprivileged spaces despite an absence of symptoms.

Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study.

Purpose: In survivors of Ebola virus disease (EVD), intraocular viral persistence raises questions about the timing and safety of cataract surgery. To the best of our knowledge, this is the first controlled study evaluating Ebola virus persistence and cataract surgery safety and outcomes in EVD survivors. Methods: Seropositive EVD survivors and seronegative controls with vision worse than 20/40 from cataract and without active intraocular inflammation were enrolled. Aqueous humor from survivors was tested with reverse transcription-polymerase chain reaction for Ebola viral RNA. Participants underwent manual small-incision cataract surgery and 1 year of follow-up examinations. Results: Twenty-two eyes of 22 survivors and 12 eyes of eight controls underwent cataract surgery. All of the aqueous samples tested negative for Ebola viral RNA. Median visual acuity improved from 20/200 at baseline to 20/25 at 1 year in survivors and from count fingers to 20/50 in controls (overall, P < 0.001; between groups, P = 0.07). After a 1-month course of topical corticosteroids, 55% of survivors and 67% of controls demonstrated at least 1+ anterior chamber cell. Twelve months after surgery, optical coherence tomography revealed a median increase in macular central subfield thickness of 42 µm compared with baseline (overall, P = 0.029; between groups, P = 0.995). Conclusions: EVD survivors and controls demonstrated significant visual improvement from cataract surgery. The persistence of intraocular inflammation highlights the importance of follow-up. The absence of detectable intraocular Ebola viral RNA provides guidance regarding the safety of eye surgery in Ebola survivors. Translational Relevance: These findings demonstrate the safety and efficacy of cataract surgery in Ebola survivors and will inform ocular surgery guidelines in this population.