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.

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.

Indications for keratoplasty in management of corneal ectasia.

PURPOSE OF REVIEW: The current review aims to describe recent advancements in treatment of corneal ectasias and its effect on indications for corneal transplantation. RECENT FINDINGS: The majority of patients affected by ectatic corneal disease use contact lenses to correct resulting astigmatism. Patients who are intolerant of contact lenses or cannot achieve acceptable vision through conservative measures could consider keratoplasty. However, continuing advancements in both nonsurgical and surgical treatments are either reducing or delaying the need for keratoplasty in patients affected by ectatic corneal disease. SUMMARY: Corneal transplantation has been the mainstay of treatment for patients with advanced ectatic corneal disease. In the past decade, numerous improvements have been occurred to make contact lenses not only more effective for visual correction, but also more comfortable. Although corneal cross-linking is the only proven treatment known to prevent progression of disease, several other therapies show early potential for those in which cross-linking is contraindicated. Patients now have access to a wider range of therapies before considering keratoplasty.

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.

Overview of Short-Term and Intermediate-Term Corneal Storage Solution: Comparison of Clinical Outcomes and Need For Future Research.

ABSTRACT: Corneal donor tissue preservation techniques have incrementally improved since the introduction of McCarey-Kaufman storage solution from short-term storage to intermediate duration of storage with the advent of organ culture and Optisol GS storage solutions. Improved understanding of the corneal endothelial cell physiology has helped in designing newer storage solutions, such as the Life 4C and Cornea Cold. The incorporation of antibiotics, ATP precursors, minerals, and vitamins has improved the viability of tissues. In addition, these modifications to the newer storage solutions have increased the endothelial longevity and metabolic activity. Despite these advances, the duration of tissue storage has largely been restricted to 2 weeks in Optisol GS and 4 weeks in organ culture. The role and cost-effectiveness of antifungal supplementation and the need for improved epithelial preservation are additional areas that need to be explored. This review intends to summarize the efficacy and viability of donor corneas in different tissue storage solution and compare clinical outcomes while providing an insight into the challenges in developing newer methods of corneal preservation.

Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes.

ABSTRACT: Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

Current and future therapies for persistent corneal epithelial defects and neurotrophic keratopathy.

PURPOSE OF REVIEW: The corneal epithelium is a crucial barrier against pathogens, and when disrupted in the setting of certain underlying risk factors such as neurotrophic keratopathy (NK), may result in persistent epithelial defects (PEDs) of the cornea. Management is challenging and may require a variety of different approaches ranging from conservative medical therapy to surgical intervention. The purpose of this review is to provide an update on current and potential future therapeutic options for PEDs and NK. RECENT FINDINGS: Recent research has yielded promising results for numerous novel therapies aimed at treating PEDs. Many of these attempt to stimulate healing at the cellular level, via signaling of corneal epithelial differentiation, migration, and proliferation. Considerable advances have also been made regarding medical and surgical promotion of corneal re-innervation and restoration of corneal sensitivity to directly address the underlying NK condition. SUMMARY: Together with the current well established therapeutic options available for PEDs and NK, growing research on newer alternatives suggest increasing potential for both more effective and more convenient therapies for these difficult situations.

Sodium-Sensitive Contact Lens for Diagnostics of Ocular Pathologies.

The ability to measure all the electrolyte concentrations in tears would be valuable in ophthalmology for research and diagnosis of dry eye disease (DED) and other ocular pathologies. However, tear samples are difficult to collect and analyze because the total volume is small and the chemical composition changes rapidly. Measurements of electrolytes in tears is challenging because typical clinical assays for proteins and other biomarkers cannot be used to detect ion concentrations tears. Here, we report the contact lens which is sensitive to sodium ion (Na+), one of the dominant electrolytes in tears. The Na ions in tears is diagnostic for DED. Three sodium-sensitive fluorophores (SG-C16, SG-LPE and SG-PL) were synthesized by derivatizing the sodium green with 1-hexadecyl amine, 1-oleoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine or poly-L-lysine, respectively. These probes were bound to modern silicone hydrogel (SiHG) contact lens, Biofinity from Cooper Vision. Doped lenses were tested for sodium ion dependent spectral properties of probes within the contact lens. The probes displayed changes in intensity and lifetime in response to Na+ concentration, were completely reversible, no significant probe wash-out from the lenses, were not affected by proteins in tears and were not removed after repeated washing. These results are the first step to our long-term goal, which is a lens sensitive to all the electrolytes in tears. We presented design, synthesis and implementation of three new sodium sensitive probes within a silicon hydrogel lens. Contact lenses to measure the other electrolytes in tears can be developed using the same approach by synthesis and testing of new ion-sensitive fluorophores.

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.

Is There a Cutoff in Favor of Penetrating Keratoplasty Rather than Endothelial Keratoplasty for Long-Standing Endothelial Decompensation?

Endothelial keratoplasty (EK) has evolved to become the standard of care over traditional penetrating keratoplasty (PK) for treating isolated corneal endothelial disease. EK provides numerous advantages including faster, more reliable visual rehabilitation, along with a lower allograft rejection rate. There are some situations, however, in which EK may not necessarily be the best option, and PK should at least be considered. In such situations, a careful weighing and balancing needs to be done in conjunction with the patient.

Fluorescent contact lens for continuous non-invasive measurements of sodium and chloride ion concentrations in tears.

Rapid and non-invasive measurement of hydration status is medically important because even mild levels of dehydration can have a significant impact on physical and cognitive performance. Despite the potential value of determining whole-body hydration based on the electrolytes found in tears, very few tests are available. An area of intense interest is the development of a contact lens which could measure ion concentrations in tears, specifically that of sodium (Na+) and chloride (Cl-) ions, the dominant electrolytes in blood plasma and tears. Here, we describe a method to make fluorescent contact lenses which allow determination of Na+ and Cl- ion concentrations in tears. Fluorophores known to be sensitive to Na+ and Cl- were derivatized to bind non-covalently to two commercially-available silicone hydrogel (SiHG) contact lenses-the Biofinity (Comfilcon A) or MyDay (Stenfilcon A) lenses. The sodium- and chloride-sensitive fluorophores displayed spectral changes in the physiological range for Na+ and Cl- ions in tears. The lenses for both Na+ and Cl- ions were completely reversible. The sodium responses were not sensitive to protein interference including human lysozyme, human serum albumin and mucin type 2. The chloride sensitivity was similar with both lenses, but the sodium-sensitive range was different in the Biofinity and MyDay lenses. We also fabricated a lens with both the Na+ and Cl- probes in a single MyDay lens resulting in a contact lens that independently measured Na+ and Cl- concentrations without physical separation of the fluorophores. Our findings indicated that a sodium and chloride-sensitive contact lens (NaCl-lens) could be used for rapid non-invasive detection of whole-body hydration, as well as associated diseases or other infections.

Postoperative Endothelial Cell Density Is Associated with Late Endothelial Graft Failure after Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To determine whether preoperative endothelial cell density (ECD) and postoperative ECD after Descemet stripping automated endothelial keratoplasty (DSAEK) are associated with late endothelial graft failure (LEGF) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, randomized clinical trial. PARTICIPANTS: A total of 1007 individuals (1223 study eyes), mean age 70 years, undergoing DSAEK for Fuchs' dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE) (6% of eyes) and followed for up to 5 years. METHODS: Central ECD was determined by a central image analysis reading center. Preoperative ECD was determined for 1209 eyes that did not fail and 14 eyes that experienced LEGF. The ECD at 6 and 12 months after DSAEK, the change in ECD from preoperative to 6 and 12 months, surgeon-reported operative complications, and postoperative graft dislocation were investigated for an association with LEGFs unrelated to other postoperative events. Univariable and multivariable Cox proportional hazards regression models were used to assess associations. MAIN OUTCOME MEASURES: Late endothelial graft failure and its associations with pre- and postoperative ECD and operative complications. RESULTS: The cumulative probability of LEGF was 1.3% (95% confidence interval [CI], 0.8%-2.4%). Median (interquartile range [IQR]) preoperative ECDs were similar for eyes with LEGF (2523; 2367-3161) cells/mm2) and eyes without failure (2727; 2508-2973) cells/mm2) (P = 0.34). The ECD at 6 months was associated with LEGF (P < 0.001) in time-to-event analyses, whereas preoperative ECD was not (P = 0.55). The cumulative incidence (95% CI) of LEGF was 6.5% (3.0%, 14.0%) for 97 grafts with a 6-month ECD less than 1200 cells/mm2, 0.3% (0.0%, 2.4%) for 310 grafts with a 6-month ECD between 1200 and 2000 cells/mm2, and 0.6% (0.1%, 2.7%) for 589 grafts with a 6-month ECD greater than 2000 cells/mm2. In multivariable analyses, ECD at 6 months and operative complications were both associated with LEGF (P = 0.002 and P = 0.01, respectively), whereas graft dislocation was not (P = 0.61). CONCLUSIONS: In eyes undergoing DSAEK, preoperative ECD is unrelated to LEGF, whereas lower ECD at 6 months is associated with LEGF. Early endothelial cell loss after DSAEK and intraoperative complications should be minimized to improve graft survival.

Contact lens to measure individual ion concentrations in tears and applications to dry eye disease.

Dry eye disease (DED) affects millions of individuals in the United States and worldwide, and the incidence is increasing with an aging population. There is widespread agreement that the measurement of total tear osmolarity is the most reliable test, but this procedure provides only the total ionic strength and does not provide the concentration of each ionic species in tears. Here, we describe an approach to determine the individual ion concentrations in tears using modern silicone hydrogel (SiHG) contact lenses. We made pH (or H3O+, hydronium cation,/OH-, hydroxyl ion) and chloride ion (two of the important electrolytes in tear fluid) sensitive SiHG contact lenses. We attached hydrophobic C18 chains to water-soluble fluorescent probes for pH and chloride. The resulting hydrophobic ion sensitive fluorophores (H-ISF) bind strongly to SiHG lenses and could not be washed out with aqueous solutions. Both H-ISFs provide measurements which are independent of total intensity by use of wavelength-ratiometric measurements for pH or lifetime-based sensing for chloride. Our approach can be extended to fabricate a contact lens which provides measurements of the six dominant ionic species in tears. This capability will be valuable for research into the biochemical processes causing DED, which may improve the ability to diagnose the various types of DED.

Management of chronic complications associated with herpes zoster ophthalmicus.

PURPOSE OF REVIEW: Herpes zoster ophthalmicus (HZO) has the potential to cause significant visual morbidity and functional disability in patients with recalcitrant disease, keratitis, and postherpetic neuralgia. This article will review the current methods of prevention and treatment of anterior segment-related chronic complications of HZO. RECENT FINDINGS: HZO-related anterior segment ocular complications can range to include conjunctivitis, keratitis, and uveitis that can all be difficult to manage. Furthermore, many clinicians differ in their approach to disease management given the relative lack of large randomized controlled trials to guide therapy. The goal in managing complications of HZO is to reduce visual morbidity and to improve analgesia, and here, we present current recommendations for the management of anterior segment complications of HZO. SUMMARY: Recent advances in vaccine technology and the initiation of the Zoster Eye Disease Study improve the possibility of reducing the burden of disease while also further standardizing management of HZO.

Recurrent Corneal Erosions Secondary to Use of Sleep Mask.

A 31-year-old woman with a history of unusual appearing recurrent linear corneal epithelial defects and subepithelial scaring in both eyes underwent 2 years of evaluation and treatment. It was eventually discovered that the patient was using a sleep mask with excessive fabric pilling, which was found to be the source of her chronic epitheliopathy. After discontinuation of the sleep mask, the patient experienced complete resolution of symptoms. When evaluating recurrent corneal epithelial defects, external sources of repeated trauma, including sleepwear, should be investigated.

Efficacy of Amphotericin B Against Fusarium and Aspergillus in Corneal Storage Medium.

PURPOSE: The incidence of postkeratoplasty fungal infection is increasing in the United States, and our most commonly used corneal storage medium, Optisol-GS, contains antibiotics but no antifungal agents. We previously demonstrated the efficacy of amphotericin B additives in eliminating Candida albicans contaminants in Optisol-GS. The purpose of this study was to determine whether amphotericin B would also be efficacious against Fusarium solani and Aspergillus fumigatus. METHODS: Vials of Optisol-GS were supplemented with 0.255 µg/mL of amphotericin B. Half of the vials were inoculated with F. solani and half with A. fumigatus. Positive control vials were inoculated with the fungi but no amphotericin B. The vials were refrigerated, sampled, and plated at different time points. The plates were then incubated at 36°C for 48 hr after which fungal colony counts were performed. RESULTS: There was an average reduction in the growth of F. solani in the amphotericin B-supplemented vials of 44% on day 2, 79% on day 7, and 80% on day 14 when compared with the positive control vials. There was an average reduction in the growth of A. fumigatus in the amphotericin B-supplemented vials of 40% on day 2 and 14% on day 7 when compared with the positive control vials. Both amphotericin B-supplemented and control vials grew less than 2 colonies of A. fumigatus on day 14. CONCLUSIONS: This study suggests that amphotericin B additives in Optisol-GS reduce the growth of F. solani and A. fumigatus.

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.