Current state of endothelial cell therapy.

PURPOSE OF REVIEW: Currently, there is heightened interest surrounding endothelial cell therapy for the treatment of corneal edema. The purpose of this review article is to describe and summarize the background information as well as the research surrounding the emerging treatment modalities for endothelial cell therapy. RECENT FINDINGS: Marked advancements have been made in the translational research in this area, and increasing refinements have been demonstrated in the treatment protocols for cell therapy. Human clinical trials in this field are ongoing, specifically, in the area of injected human corneal endothelial cells (HCECs), with early results showing favorable safety and efficacy profiles. SUMMARY: Efficient and effective delivery of HCECs to patients with corneal edema and dysfunction now appears feasible, and the results from ongoing human clinical trials are much anticipated. Adjunct therapeutics-in the form of pharmacological agents and/or surgical techniques, such as descemetorhexis-will likely continue to play an important role in defining the future of endothelial cell therapy.

Descemet Membrane Endothelial Keratoplasty as Treatment for Late-Onset Interface Fluid Syndrome After Laser In Situ Keratomileusis.

PURPOSE: We herein present Descemet membrane endothelial keratoplasty (DMEK) as an effective surgical means of treatment for the management of interface fluid syndrome (IFS) in a series of cases with distant history of laser in situ keratomileusis (LASIK). METHODS: Three cases from a single institution were included. All patients had documented IFS in the setting of history of LASIK. All 3 patients underwent DMEK for the treatment of IFS. Visual acuity, clinical findings, pachymetry, endothelial cell count, and anterior segment optical coherence tomography were recorded. RESULTS: We describe 3 cases of late-onset IFS that developed in eyes many years after LASIK (ranging from 15 to 31 years). All 3 patients had clinically significant corneal edema and evidence of poor endothelial function at the time of IFS diagnosis. DMEK was subsequently performed in each case. All 3 eyes showed resolution of corneal edema and improvement in best-corrected visual acuity after DMEK. CONCLUSIONS: DMEK can provide successful visual and anatomical recovery in patients who have had previous LASIK and experience late-onset IFS due to endothelial cell dysfunction.

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.

Scheimpflug Corneal Tomography Anterior Chamber Depth in Descemet Stripping Endothelial Keratoplasty Recipients.

PURPOSE: Our study investigates whether preoperative anterior chamber depth (ACD) measured by Scheimpflug tomography could serve as a potential predictor of graft failure in eyes undergoing Descemet stripping endothelial keratoplasty (DSEK). METHODS: A retrospective review was conducted on patients who underwent primary or repeat DSEK between January 2020 and August 2021 at Bascom Palmer Eye Institute. Charts from 378 primary and 192 repeat DSEK patients were reviewed and ultimately 47 primary and 21 repeat DSEK patients met criteria for inclusion. Data collection included demographics, preoperative ACD, best-corrected visual acuity, and length of follow-up. RESULTS: Demographics were similar between groups, and there was no significant difference in the average best-corrected visual acuity between the single and repeat DSEK groups preoperatively. Baseline preoperative ACD was greatest in the single DSEK group (3.51 ± 0.90 mm) when compared to baseline preoperative ACD in the repeat DSEK group (3.01 ± 0.67 mm, P = 0.003). The preoperative mean ACD was smallest in the repeat DSEK group before the second DSEK (2.94 ± 0.48 mm, P = 0.001). Preoperative baseline ACD was the only variable to affect graft survival time significantly (P = 0.012). The incidence of glaucoma diagnosis was similar in both groups (42.5% vs. 42.8%, P = 0.471). The diagnosis of glaucoma and presence of incisional glaucoma surgery did not affect the graft survival time (P = 0.129, P = 0.559) or need for repeat DSEK. CONCLUSIONS: Smaller baseline preoperative Scheimpflug ACD measurement may be a possible predictor of the need for repeat DSEK. Our study found that Scheimpflug ACD decreases with subsequent DSEK failure.

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.

Outcomes of Secondary Intraocular Lens Implantation and Descemet Stripping Endothelial Keratoplasty-Comparing Staged Versus Combined Surgical Approach.

PURPOSE: The aim of this study was to compare the outcomes of staged versus combined surgical approach for secondary intraocular lens (IOL) implantation and Descemet stripping endothelial keratoplasty (DSEK). METHODS: This is a retrospective review of 124 eyes from 124 patients who underwent either staged or combined secondary IOL implantation in addition to DSEK over a 5-year period at 2 academic tertiary referral centers, between January 1, 2014, and October 1, 2019. Corrected distance visual acuity (CDVA), presence of graft detachment, primary graft failure (PGF), and cystoid macular edema were documented and analyzed. RESULTS: The CDVA for the 1- to 2- month follow-up period was significantly better in the staged group compared with the combined group ( P = 0.011). By the postoperative 6- to 9-month follow-up period, there was no significant difference in the CDVA between the groups ( P = 0.591). There was no significant difference in the incidence of PGF or graft detachment between the 2 groups ( P > 0.05). In addition, there was no significant difference in the CDVA or rate of postoperative complications between the different methods of IOL fixation. CONCLUSIONS: The short-term visual outcomes were significantly better in eyes that underwent staged secondary IOL implantation and DSEK versus the combined surgical approach, although the difference was no longer present at 6 to 9 months. There was no difference in the rate of PGF or graft detachment between the 2 groups.

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.

Outcomes of Nontuberculous Mycobacterial Keratitis After Clear Corneal Incision Phacoemulsification Surgery: A Case Series of 6 Eyes in South Florida.

PURPOSE: The purpose of this study was to present the successful management and outcomes in a series of 6 cases of culture-positive nontuberculous mycobacterial keratitis after clear corneal incision phacoemulsification surgery. METHODS: This is a case series of 6 consecutive eyes that presented at the Cornea Division at an academic institution, diagnosed with culture-positive nontuberculous mycobacterial keratitis after phacoemulsification surgery. RESULTS: Six eyes of 5 patients were included. The mean interval from cataract surgery to presentation was 7.7 weeks. All cases presented with intrastromal abscesses adjacent to corneal incisions, and 2 had scleral extension of the infection. Isolated organisms were Mycobacterium abscessus (n = 4), Mycobacterium chelonae (n = 1), and Mycobacterium mucogenicum (n = 1). All cases were treated with topical amikacin 8 mg/mL for 10.5 weeks on average. All cases received either oral clarithromycin at 500 mg twice-daily dosage or oral azithromycin at 500 mg daily. Two patients with scleral abscesses underwent surgical debridement with amniotic membrane grafts. All 6 eyes achieved infection resolution and good visual recovery, with the final visual acuity ranging from 20/20 to 20/60. None of the patients experienced recurrence of infection. CONCLUSIONS: Prompt medical treatment with combined topical and oral therapy can lead to infection resolution and favorable visual recovery. Early surgical intervention can ensure good outcomes in cases of scleral extension.

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.

Descemet Membrane Endothelial Keratoplasty for Corneal Edema and Visually Significant Descemet Membrane Scrolls Due to Syphilitic Keratitis.

ABSTRACT: The presence of Descemet membrane scrolls is an uncommon finding reported in syphilitic interstitial keratitis. We herein describe a novel surgical strategy for this entity; this report demonstrates that Descemet membrane endothelial keratoplasty surgery can be performed with excellent visual outcomes in the event of corneal edema as a late sequela of syphilitic keratitis.

Acute Corneal Transplant Rejection After COVID-19 Vaccination.

PURPOSE: The purpose of this report was to describe 4 cases of acute corneal transplant rejection occurring in association with coronavirus disease 2019 (COVID-19) mRNA vaccination. METHODS: Four patients with prior keratoplasty developed presumed immunologic rejection after the mRNA-1273 vaccination for coronavirus 2 (SARS-CoV-2). Case 1 had received Descemet membrane endothelial keratoplasty 6 months ago and presented with endothelial graft rejection 3 weeks after the first vaccine dose. Case 2 had undergone penetrating keratoplasty 3 years previously and presented with acute endothelial rejection 9 days after the second vaccine dose. Case 3 had prior Descemet stripping automated endothelial keratoplasty (DSAEK) and began experiencing symptoms of endothelial graft rejection 2 weeks after the second vaccine dose. Case 4 presented with endothelial rejection of the penetrating keratoplasty graft 2 weeks after the second vaccine dose. RESULTS: Frequent topical corticosteroids alone were initiated in all 4 cases. In case 1, the endothelial rejection line appeared fainter with improvement in visual acuity and corneal edema 5 weeks after diagnosis. Case 2 experienced complete resolution of corneal stromal edema and rejection line 6 weeks after diagnosis. Cases 3 and 4 have both experienced initial improvement with steroid treatment as well. CONCLUSIONS: These cases suggest acute corneal endothelial rejection may occur soon after either dose of the COVID-19 mRNA vaccine. Prompt initiation of aggressive topical steroid therapy may result in complete resolution of clinical signs and symptoms. Further studies are needed to elucidate the causal mechanism of corneal graft rejection after COVID-19 vaccination.

Refractive Outcomes in Fuchs' Endothelial Corneal Dystrophy: Conventional and Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To investigate the refractive outcomes of eyes with Fuchs' endothelial corneal dystrophy (FECD) following phacoemulsification. METHODS: This is a retrospective chart review of patients with FECD who underwent phacoemulsification. Manifest refraction at the early postoperative period (1-6 weeks) and late postoperative period (3-12 months) was collected. The spherical equivalent (SE) and variance of SE from target in diopters (D) were analyzed. RESULTS: A total of 219 eyes from 175 FECD patients (73 FLACS, 146 conventional phacoemulsification) were included. In the early postoperative period, when comparing variance from intended target, 62% (n=126) had a SE variance of ≤0.5 D, 22% (n=44) >0.5 D and ≤1 D, and 17% (n=34) >1 D. In the late postoperative period, 62% (n=85) had a SE variance of ≤0.5 D, 19% (n=26) >0.5 D and ≤1 D, and 20% (n=27) >1 D. There was no difference in the variance of SE comparing FLACS versus conventional phacoemulsification in either the early postoperative period (p=0.78) or the late postoperative period (p=0.29). CONCLUSION: Patients with mild-to-moderate FECD had favorable refractive outcomes with phacoemulsification. There was no difference in refractive outcomes in eyes with FECD between the group that underwent FLACS versus the group that underwent conventional phacoemulsification.

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.

mHOMR: a prospective observational study of an automated mortality prediction model to identify patients with unmet palliative needs.

OBJECTIVE: Identification of patients with shortened life expectancy is a major obstacle to delivering palliative/end-of-life care. We previously developed the modified Hospitalised-patient One-year Mortality Risk (mHOMR) model for the automated identification of patients with an elevated 1-year mortality risk. Our goal was to investigate whether patients identified by mHOMR at high risk for mortality in the next year also have unmet palliative needs. METHOD: We conducted a prospective observational study at two quaternary healthcare facilities in Toronto, Canada, with patients admitted to general internal medicine service and identified by mHOMR to have an expected 1-year mortality risk of 10% or more. We measured patients' unmet palliative needs-a severe uncontrolled symptom on the Edmonton Symptom Assessment Scale or readiness to engage in advance care planning (ACP) based on Sudore's ACP Engagement Survey. RESULTS: Of 518 patients identified by mHOMR, 403 (78%) patients consented to participate; 87% of those had either a severe uncontrolled symptom or readiness to engage in ACP, and 44% had both. Patients represented frailty (38%), cancer (28%) and organ failure (28%) trajectories were admitted for a median of 6 days, and 94% survived to discharge. CONCLUSIONS: A large majority of hospitalised patients identified by mHOMR have unmet palliative needs, regardless of disease, and are identified early enough in their disease course that they may benefit from a palliative approach to their care. Adoption of such a model could improve the timely introduction of a palliative approach for patients, especially those with non-cancer illness.

Challenges in management of the Boston Keratoprosthesis Type 1.

PURPOSE OF REVIEW: The Boston Keratoprosthesis Type 1 was pioneered by Claes Dohlman several decades ago. Since its inception, the device has undergone multiple revisions to address challenges associated with retroprosthetic membrane formation, retention, extrusion, stromal melt and endophthalmitis. Although visual outcomes and retention rates have improved, challenges, especially glaucoma, remain. RECENT FINDINGS: The Boston Keratoprosthesis Type I device has seen an increase in popularity because of the improvement in rates of retention and visual rehabilitation. Recent outcome studies have allowed clinicians to identify diagnoses and indications that can lead to more favorable results with the Boston Keratoprosthesis Type I device. SUMMARY: The Boston Keratoprosthesis Type I device continues to play a vital role in visual rehabilitation for eyes with very low chance of realistic allograft survival -- such as in eyes where corneal grafting is considered high-risk: eyes with corneal limbal stem cell failure, extensive deep corneal stromal neovascularization, and multiple allograft failures. This review article summarizes the perioperative and postoperative challenges, as well as other considerations associated with the device.

Femtosecond Laser-Assisted Cataract Surgery: Does It Improve Outcomes in Fuchs Endothelial Corneal Dystrophy?

The role of femtosecond laser -assisted cataract surgery in patients with Fuchs endothelial corneal dystrophy remains poorly defined. This invited commentary examines the current evidence surrounding this often-debated topic.

Barriers and Facilitators to Early Rehabilitation in the ICU: A Theory Driven Delphi Study.

OBJECTIVES: There is conflicting evidence for the effectiveness of early rehabilitation in the intensive care and marked variation in rates of implementation in practice. We aimed to identify barriers and facilitators to early rehabilitation in mechanically ventilated patients and their relevance to practice, as perceived by key ICU clinicians across North America. DESIGN: A Delphi study using the Theoretical Domains Framework, consisting of an initial qualitative round and subsequent quantitative rounds, was conducted to gather clinician agreement and perceived importance of barriers and facilitators to early rehabilitation. The survey included questions on the range of individual, sociocultural, and broader organizational influence on behaviors. SETTING: Clinical practice in North America. SUBJECTS: Four clinician groups (intensive care physicians, nurses, therapists, and respiratory therapists). INTERVENTIONS: A three-round Delphi study. MEASUREMENTS AND MAIN RESULTS: Fifty of 74 (67%) of invited clinicians completed the study. Agreement and consensus with Delphi survey items were high in both rounds within and between professional groups. Agreement was highest for items related to the domain "Beliefs about Consequences" (e.g., mortality reduction) and lowest for items related to the domain "Behavioral Regulation" (e.g., team discussion of barriers). Beliefs expressed about improved mortality and improvements in a variety of other long-term outcomes were not consistent with the current evidence base. Individual agreement scores changed very little from Round 2 to Round 3 of the Delphi, suggesting stability of beliefs and existing consensus. CONCLUSIONS: This study identified a wide range of beliefs about early rehabilitation that may influence provider behavior and the success and appropriateness of further implementation. The apparent inconsistency between the optimism of stakeholders regarding mortality reductions and a low level of implementation reported elsewhere represent the most major challenge to future implementation success. Other foci for future implementation work include planning, barriers, feedback, and education of staff.