Trends and Surgeon Variations in Early Regrafts After Endothelial Keratoplasty: Analysis of the National Medicare Data Set.

PURPOSE: The aims of this study were to determine national-level trends in early regraft rates and examine patient-level and surgeon-level characteristics associated with early regrafts. METHODS: This was a retrospective, cohort study. We identified beneficiaries aged 65 years or older in the 2011 to 2020 Medicare carrier claims data set who underwent Endothelial keratoplasty (EK) and subsequently underwent an early regraft. The incidence of early regraft for each year was calculated and patient-level and surgeon-level characteristics associated with regrafts were examined using a multivariable regression model. RESULTS: Of 114,383 EK procedures, 4119 (3.60%) were followed by an early regraft, with no significant variations in the rates between years ( P = 0.59). Factors associated with higher odds of early regraft were Black compared with White race (OR 1.151; 95% confidence interval (CI) 1.018-1.302) and the highest quartile of income versus the lowest quartile (OR 1.120; 95% CI 1.002-1.252). Factors associated with lower odds were female sex (OR 0.889; 95% CI 0.840-0.942), receiving surgery in a hospital-based outpatient department versus an ambulatory center (OR 0.813; 95% CI 0.740-0.894), and having a surgeon with the highest quartile of annual EK volume versus the lowest (OR 0.726; 95% CI 0.545-0.967). Early regraft rates among surgeons ranged from 0% to 58.8% with a median [interquartile range] of 3.13 [0-6.15]. CONCLUSIONS: We found no significant increases in the early regraft rates over the past decade in the United States. Patient male sex and Black race, ambulatory surgery center-based location of the surgery, and low surgeon EK volume were associated with early regrafts. Substantial surgeon variability in regraft rates may indicate opportunities for improvement through development of best practices on perioperative management and patient counseling.

Predictors of intraocular pressure reduction after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a prospective trial.

PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Optimizing the ocular surface prior to cataract surgery.

PURPOSE OF REVIEW: Ocular surface disease can significantly impact the outcomes of cataract surgery. Recent studies have examined the efficacy of several new dry eye disease (DED) therapies, the extent to which epithelial debridement affects keratometric measurements in epithelial basement membrane dystrophy (EBMD) and Salzmann nodular degeneration (SND), and the predictability of refractive error following combined pterygium and cataract removal. This review aims to incorporate these newer studies in updating and further emphasizing the need for careful management and optimization of common ocular surface conditions prior to cataract surgery. RECENT FINDINGS: Common ocular surface conditions such as DED, EBMD, SND, and pterygium can cause significant irregular astigmatism and higher-order aberrations. Their resolution can substantially alter biometry measurements in preparation for cataract surgery, affecting the final visual outcome. Newer therapies for DED, such as topical lifitegrast and thermal pulsation treatment, can aid in this optimization process. If superficial keratectomy or excisions of lesions on the ocular surface are performed, sufficient healing time is needed to allow the ocular surface to reach stability prior to biometry measurements. SUMMARY: Ocular surface optimization is key to successful cataract surgery planning and reaching desired outcomes.

Survey of Corneal Surgeons' Attitudes Regarding Keratoplasty Rejection Risk Associated With Vaccinations.

PURPOSE: To investigate the attitudes and practice of corneal specialists if patients with keratoplasty sought advice regarding common vaccinations and risk for potential graft rejection. METHODS: An online questionnaire was posted on the Kera-net listserv and the EuCornea Web site in early 2020. Attitudes toward vaccinations and keratoplasty were obtained. Decision making for common keratoplasty (endothelial keratoplasty, deep anterior lamellar keratoplasty, and penetrating keratoplasty) scenarios at early and late time points was explored regarding the herpes zoster and influenza vaccines. RESULTS: There were 142 respondents: 51.1% (70/137) specifically advise their patients with keratoplasty to get all vaccinations; 19.7% (27/137) stated clinical experience of a vaccine-associated rejection episode; 42.2% (57/135) were unaware of any such cases; and 64% (27/42) of those concerned would recommend delay if within 3 months of transplant surgery, recent corneal infection, or a recent rejection episode. The 2245 total responses to 18 clinical scenarios demonstrated wide variability in management of grafts in the setting of vaccination. Generally, 45.9% would not alter management, 26.2% would increase frequency of topical steroids, and 22.2% would recommend delay to vaccinations. Increased concern was expressed with recent surgery, live zoster vaccine and higher-risk penetrating keratoplasty scenarios. CONCLUSIONS: Nearly half of the respondents do not alter management in the setting of keratoplasty and zoster and/or influenza vaccinations. Anecdotal rejection episodes possibly associated with vaccinations were reported by some. Vaccine-related rejection has not been shown in higher-level research, but that has not eliminated clinical concerns. Prospective research into the true vaccine-related risks in keratoplasty is necessary if evidence-based management guidelines are to be developed or definitive reassurance provided.

Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM).

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.

Corneal Changes After Belantamab Mafodotin in Multiple Myeloma Patients.

OBJECTIVES: To describe progressive corneal microcyst-like epithelial changes (MECs) that developed in patients treated with the investigational drug belantamab mafodotin (belamaf) for refractory multiple myeloma (MM). METHODS: This is a single center case series of patients with MM receiving the investigational drug belamaf. RESULTS: All 12 patients included in this analysis who were treated with belamaf developed MECs that initially appeared in the peripheral cornea and progressed centrally with time. Cessation of therapy resulted in regression of the MECs first in the periphery then centrally. Microcyst-like epithelial changes recurred in all patients on retreatment. With prolonged therapy, eight patients developed corneal staining patterns suggestive of limbal stem cell dysfunction (LSCD). CONCLUSION: We describe MECs and LSCD associated with systemic administration of belamaf. Further study is needed to determine the etiology and composition of the MECs and the mechanism of limbal stem cell involvement.

Correction to: Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study.

The authors of the above mentioned article would like to highlight the following corrections, based upon recent changes to the FDA label and guidance on the use of belamaf.

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study.

INTRODUCTION: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. METHODS: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. RESULTS: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. CONCLUSION: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03525678.

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Effects of Glaucoma Tube Surgery on Corneal Endothelial Cells: A Review.

The etiology of corneal decompensation after aqueous shunt implantation remains poorly understood. With the use of anterior segment optical coherence tomography and specular microscopy, the relationship of these implants to the surrounding tissues can be investigated over time. This article will review the current knowledge pertaining to endothelial cell loss related to glaucoma and surgery and highlight possible causes that have been proposed for endothelial cell loss after aqueous shunt implantation.

Correlation of Serial Scleral and Corneal Pneumatonometry.

PURPOSE: To evaluate the usefulness of scleral pneumatonometry as an alternative for corneal measurements of intraocular pressure (IOP) over a broad range of IOPs. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study was conducted in the University of California, San Francisco, Retina Clinic between August and November 2013 in 33 adult patients (age range, 34-94 years; mean ± standard deviation, 74.1±13.4 years) receiving anti-vascular endothelial growth factor intravitreal injections, which transiently increase IOP. METHODS: Corneal pachymetry and serial corneal and temporal scleral pneumatonometry (baseline, immediately after, and 10, 20, and 30 minutes after injection) were collected. One-time baseline corneal and scleral pneumatonometry readings were obtained in the noninjected eye. MAIN OUTCOME MEASURES: Correlation analysis and a Bland-Altman plot were used to evaluate reliability and agreement between scleral and corneal measurements of IOP. A linear mixed model was used to determine the relationship between measurements and to perform covariate analyses. RESULTS: Scleral and corneal pneumatonometry showed nearly 1:1 linear correlation, although scleral pneumatonometry was biased toward higher values (r = 0.94; P < 0.001). Scleral pneumatonometry averaged 9.0 mmHg higher than corneal pneumatonometry (95% limits of agreement, -1.5 to 19.5 mmHg). A linear mixed model resulted in the following equation: corneal IOP = 1.04 × scleral IOP - 10.37. Age, central corneal thickness, laterality, and glaucoma and lens status did not impact this relationship. The difference between corneal and scleral pneumotonometry was correlated between the two eyes of individual patients (r = 0.75; P < 0.001). CONCLUSIONS: Differences between serial scleral measurements reflect differences between serial corneal measurements. Scleral pneumatonometry should be considered as an alternative to corneal pneumatonometry for following patients in whom corneal measurements are unreliable or unobtainable.

Diffuse Epithelial Downgrowth Associated With an Extruded Anterior Chamber Intraocular Lens Haptic.

BACKGROUND: Anterior chamber intraocular lenses (ACIOL) have been known to be associated with several complications, including endophthalmitis. We present a patient who developed another type of severe complication: epithelial downgrowth associated with an extruded footplate of an ACIOL. METHODS: Case report. RESULTS: A 70-year-old schizophrenic woman underwent implantation of an ACIOL during cataract extraction that was complicated by posterior capsular rupture, erratic patient movement, conversion to extracapsular cataract extraction (ECCE), and vitreous loss in her left eye. She subsequently presented with progressively decreasing vision, and she was found to have extensive epithelial downgrowth that also resulted in neovascularization of the iris and recurrent hyphemas. The patient elected to have the ACIOL explanted, and at the time of the surgery, it was noted that one of the footplates of the ACIOL was protruding through the original ECCE wound. We believe that the extrusion of this footplate was one contributing factor toward severe epithelial downgrowth. CONCLUSIONS: Although exposure of an ACIOL haptic is a very rare occurrence, it can have severe consequences, including epithelial downgrowth.