Incidence and Mitigation of Corneal Pseudomicrocysts Induced by Antibody-Drug Conjugates (ADCs).

Purpose of Review: This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs). Recent Findings: ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity. Summary: Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

Noninfectious Outcomes of Intravitreal Antibiotic Steroid Injection and Topical Nonsteroidal Antiinflammatory Drugs Versus Triple Drop Therapy After Cataract Surgery.

PURPOSE: To compare noninfectious outcomes of intravitreal antibiotic steroid (IVAS) injection (moxifloxacin-triamcinolone) and postoperative topical nonsteroidal antiinflammatory drugs (NSAID) with a standard 3-drop therapy (TDT) regimen (topical antibiotic, steroid, and NSAID) in patients after cataract surgery. DESIGN: Retrospective comparative clinical cohort study. METHODS: In 3 study centers in the United States, a total of 2143 eyes (N = 2143 patients) underwent cataract surgery with IVAS-NSAID or TDT between 2017 and 2022. Preoperative data were included, including patients' age, iris color, medical history, and ocular history. Postoperative data, including best-corrected visual acuity, intraocular pressure (IOP), and the need for IOP-lowering medications, were recorded at 1-week, 1-month, and 6-month time points. The primary outcome measures were postoperative complications, defined as persistent anterior chamber inflammation, persistent corneal edema (PCE), rebound inflammation, and cystoid macular edema, were compared between the 2 groups. RESULTS: There were 1079 eyes in the IVAS-NSAID group and 1064 eyes in the TDT group. Best-corrected visual acuity and IOP were similar between IVAS-NSAID and TDT eyes at all time points. A portion (11.6%) of TDT eyes experienced postoperative complications compared with 6.5% in IVAS-NSAID eyes (P < .001). Femtosecond laser-assisted cataract surgery was associated with increased rates of PCE in IVAS-NSAID eyes, and eyes with dark irides had a higher incidence of cystoid macular edema, PCE, and rebound inflammation in the IVAS-NSAID group. CONCLUSION: The IVAS-NSAID regimen overall had similar postoperative outcomes and fewer complications compared with the TDT regimen. IVAS-NSAID may be considered a safe alternative to topical regimens in non-femtosecond laser-assisted cataract surgery and patients with light irides.

Biomarkers of Pediatric Cataracts: A Proteomics Analysis of Aqueous Fluid.

Cataracts are among the most common causes of childhood vision loss worldwide. This study seeks to identify differentially expressed proteins in the aqueous humor of pediatric cataract patients. Samples of aqueous humor were collected from pediatric and adult cataract patients and subjected to mass spectrometry-based proteomic analysis. Samples of pediatric cataracts were grouped by subtype and compared to adult samples. Differentially expressed proteins in each subtype were identified. Gene ontology analysis was performed using WikiPaths for each cataract subtype. Seven pediatric patients and ten adult patients were included in the study. Of the pediatric samples, all seven (100%) were male, three (43%) had traumatic cataracts, two (29%) had congenital cataracts, and two (29%) had posterior polar cataracts. Of the adult patients, seven (70%) were female and seven (70%) had predominantly nuclear sclerotic cataracts. A total of 128 proteins were upregulated in the pediatric samples, and 127 proteins were upregulated in the adult samples, with 75 proteins shared by both groups. Gene ontology analysis identified inflammatory and oxidative stress pathways as upregulated in pediatric cataracts. Inflammatory and oxidative stress mechanisms may be involved in pediatric cataract formation and warrant further investigation.

Ocular Injuries From Drive-by Paintball Shootings.

PURPOSE: To characterize ocular injuries from drive-by paintball shootings with a focus on the severity of injuries sustained, clinical management, and visual outcomes. DESIGN: Retrospective, interventional case series. METHODS: Setting: University practice and emergency department. PATIENT POPULATION: Patients evaluated by the ophthalmology service for paintball injuries. OBSERVATION PROCEDURE: Age, sex, eye laterality, mechanism of injury, initial best-corrected visual acuity (BCVA), and initial diagnosis. MAIN OUTCOME MEASURES: Clinical intervention(s), BCVA at last follow-up visit, and severity of injuries with a focus on ruptured globes. RESULTS: Twenty patients suffered unilateral ocular injuries from drive-by paintball shootings between January 2020 and December 2021. The median follow-up interval was 7.1 weeks (range: 3 days to 11.4 months). The average patient age at presentation was 36.6 years (range: 13-64 years). Fourteen patients (70%) had an initial BCVA of counting fingers or worse. Six patients (30%) suffered a ruptured globe injury requiring surgical repair, of whom 3 (15%) underwent subsequent evisceration. Twelve patients (60%) suffered ocular injuries requiring surgical intervention. Fifteen ocular surgeries were performed on 9 patients (45%) at our institution with 3 patients referred to outside providers for definitive surgical management due to insurance. BCVA at last follow-up visit was no light perception in 5 patients. CONCLUSIONS: The severity of injury after paintball-induced ocular trauma is higher in this case series than what has previously been reported in the literature. Paintball guns can cause devastating ocular injury when used as an assault weapon, and their use in unregulated settings bears further scrutiny.

Corneal perforation in ocular graft-versus-host disease.

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.

Leukemic and Lymphomatous Optic Neuropathy: A Case Series.

BACKGROUND: Optic neuropathy in the context of leukemia and lymphoma raises concern for central nervous system involvement or relapse and warrants prompt evaluation and treatment. To date, a gold standard for the diagnosis and management of leukemic optic neuropathy has yet to be established. METHODS: Case series and review of the literature. Two illustrative cases were selected to discuss their treatment course and outcome. RESULTS: We report 7 cases of patients with leukemia or lymphoma presenting with optic nerve infiltration. All patients received steroid therapy for presumed infiltrative optic neuropathy, and 4 patients underwent radiation therapy. Along with systemic chemotherapy, all patients received intrathecal chemotherapy except one. Three patients received chimeric antigen receptor T-cell therapy. CONCLUSIONS: Leukemic and lymphomatous optic neuropathy is difficult to diagnose and treat, and there is no gold standard for diagnosis or treatment in the current literature. We help clarify how this disease should be approached in a multidisciplinary fashion and on an individual basis to correctly diagnose and treat the vision loss, while considering the patient's long-term prognosis based on their systemic disease.

Refractive and keratometric outcomes of supervised novice surgeon-performed limbal relaxing incisions: 1-year results.

PURPOSE: To report refractive and keratometric astigmatism outcomes of resident-performed limbal relaxing incisions (LRIs) during cataract surgery. SETTING: Tertiary care academic teaching hospital. DESIGN: Retrospective case series. METHODS: The length, location, and number of LRIs were determined preoperatively using an online calculator. Variables studied were preoperative keratometry and postoperative uncorrected and corrected distance visual acuity, refraction, and keratometry at 1-month, 3-month, and 12-month visits (POM1, POM3, and POM12, respectively). Subgroup analysis was performed on amount and type of astigmatism. The astigmatism double-angle plot tool and analysis of with-the-wound (WtW) and against-the-wound (AtW) changes were used to assess the effect of astigmatism correction at POM1, POM3, and POM12 visits. RESULTS: In 118 eyes, a higher percentage of eyes demonstrated refractive astigmatism 0.25 diopter (D) or less, 0.50 D or less, 0.75D or less, and 1.0 D or less at POM1 and POM12 (all P < .05) compared with preoperative keratometric astigmatism. Subgroup analysis showed improvement in all groups and types of astigmatism (P < .01). Patients achieved a statistically significant reduction of keratometric astigmatism at POM1, POM3, and POM12 (all P ≤ .0001) relative to baseline, and changes differed significantly based on the preoperative amount of astigmatism (all P ≤ .0001, with greater reductions associated with higher baseline astigmatism) but not by location of the steep meridian. There were significant WtW-AtW changes at POM1, POM3, and POM12. Regression of effect after 1 month was approximately 0.11 D. CONCLUSIONS: Resident-performed LRIs achieved effective and sustained reduction of both refractive and keratometric astigmatism regardless of meridian or magnitude of astigmatism for at least 1 year postoperatively.

Management of severe epithelial versus fibrous downgrowth following trabeculectomy: Case report and literature review.

PURPOSE: To describe the presentation and management of a patient with epithelial versus fibrous downgrowth following trabeculectomy surgery and review relevant literature regarding this complication after intraocular surgery. OBSERVATIONS: A 52-year-old monocular African-American woman was referred for management of presumed epithelial versus fibrous downgrowth following trabeculectomy surgery. The patient was initially treated with intracameral injections of 5-fluorouracil (x2) and bevacizumab (x1). Cataract extraction, membranectomy, and a third intracameral 5-fluorouracil injection were performed. Intraocular pressure (IOP) elevation was subsequently managed with a superotemporal Ahmed FP7 glaucoma drainage device in the sulcus, followed by an inferonasal Baerveldt 350 glaucoma drainage device in the sulcus. The downgrowth has not progressed and the intraocular pressure remains controlled at the most recent follow-up. CONCLUSIONS: This case underscores the risk of this complication following trabeculectomy, the role of a combined medical and surgical approach to management, and the possible need for multiple surgical interventions to control IOP. A review of the literature regarding epithelial and fibrous downgrowth after intraocular surgery was conducted, which highlighted the aggressive nature of these conditions and the range of therapeutic approaches that have been described.

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.

Aftermarket effects of cenegermin for neurotrophic keratopathy in pediatric patients.

PURPOSE: Neurotrophic keratopathy (NK) is a rare condition characterized by poor corneal sensation and healing. Cenegermin (topical recombinant nerve growth factor) has gained traction as a medical therapy for NK in recent years, and is FDA-approved for patients over two years old. However, no major trials have demonstrated the drug's efficacy in children. This study reviews the outcomes of cenegermin therapy in a pediatric patient population. METHODS: Retrospective case series of patients from three tertiary referral institutions who 1) initiated an 8-week course of cenegermin therapy, and 2) were 18 years or less at time of treatment initiation. RESULTS: Eight pediatric patients, with a total of nine affected eyes, underwent cenegermin therapy. All eight patients had previously trialed other NK-specific treatments, none of which had been entirely successful. Five patients (63%) completed the full eight-week therapy course. Five patients (63%) experienced clinical improvement not attributed to another treatment, through improved corneal ulcer stage (n = 5) and best-corrected visual acuity (n = 2). Clinical improvements persisted through a mean recurrence-free period of 10 months. Adverse effects reported during therapy included ocular pain, difficulty sleeping, and continued corneal thinning. CONCLUSION: The results provide modest support for the use of cenegermin in pediatric patients with neurotrophic keratopathy. The primary benefit was an improvement in corneal epithelial stability. Clinicians should be aware that pre-existing corneal scarring in NK may significantly limit the ability of cenegermin alone to improve visual acuity, and should closely monitor the corneal epithelial status during therapy in pediatric patients.

Atypical Keratitis Caused by Rothia Dentocariosa.

Purpose: To report a case of atypical keratitis caused by Rothia dentocariosa.Methods: Retrospective case review.Results: A 49 year-old woman of South Asian descent presented with a non-discrete corneal ulcer with a small overlying epithelial defect in the right eye. Cultures were obtained, a topical fluoroquinolone was continued, and a topical steroid was added. The following day, the infiltrate was noted to have worsened and developed a branching appearance. Antifungals were initiated. The culture grew Rothia dentocariosa. A series of intrastromal cefuroxime injections, followed by topical penicillin G drops, led to complete resolution within 8 weeks. A review of the literature revealed only one previously reported case of Rothia dentocariosa keratitis.Conclusions: Rothia dentocariosa may cause an atypical keratitis requiring a prolonged treatment course for resolution. In our case, a combination of cefuroxime and penicillin was effective.

Resolution of Acanthamoeba Keratitis with Adjunctive Use of Oral Miltefosine.

Purpose: To report a series of cases demonstrating the resolution of Acanthamoeba keratitis (AK) with adjunctive use of oral miltefosine.Methods: Retrospective case series.Results: The first case was a 27-year-old female who presented with severe pain and photophobia. The diagnosis of AK was made with confocal microscopy, which revealed a significant burden of stromal cysts. After approximately 2 weeks of adjunctive oral miltefosine therapy, there was a severe inflammatory response within the cornea followed by quick resolution of the AK. The second case was a 31-year-old male in whom the diagnosis of AK was confirmed by culture and polymerase chain reaction. Adjunctive oral miltefosine was started 3 months after presentation, leading to a quick resolution.Conclusions: Oral miltefosine may have cysticidal properties and should be considered as adjunctive therapy for the treatment of AK, particularly in cases with a significant burden of cysts or in cases recalcitrant to other treatments.

Severe Corneal Hydrops With Suspected Posterior Stromal Rupture Managed With Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty.

PURPOSE: To describe severe acute corneal hydrops in a patient with previously undiagnosed keratoconus, in which anterior segment optical coherence tomography (AS-OCT) revealed a protruding ridge of tissue on either side of Descemet membrane (DM) break, treated successfully with ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK). METHODS: A case report. RESULTS: A 32-year-old man presented with severe corneal hydrops in OS. He was treated conservatively with hypertonic saline. Serial AS-OCT revealed persistent edema and haze overlying a break in DM, with a ridge of protruding tissue on either side. Based on these findings, UT-DSAEK was performed. Intraoperatively, the ridge of tissue remained firmly adhered after DM removal and was felt to possibly represent posterior stroma. The patient's uncorrected visual acuity improved to 20/80. Literature review revealed 1 case with similar AS-OCT findings who underwent penetrating keratoplasty; histopathology was reported to show Descemet scrolls on either side of the break, but our analysis of this and other reports suggest that an additional layer of tissue is contained within the scroll along with DM. CONCLUSIONS: This case demonstrates severe corneal hydrops in the setting of keratoconus, in which AS-OCT revealed a ridge of protruding tissue on either side of a break in DM. UT-DSAEK led to resolution of corneal edema and improvement in stromal haze and visual acuity. Further research is required to determine the precise role of endothelial keratoplasty and potential role of posterior stromal rupture in some cases of acute corneal hydrops.

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.