Faculty Bibliography

Objective/UNASSIGNED:To report a case of ocular mucosa-associated lymphoid tissue (MALT) lymphoma presenting with peripheral ulcerative keratitis. Methods/UNASSIGNED:A 58-year-old man with a history of vitreous syneresis in both eyes and glaucoma presented with an abnormal, painful sensation of the left eye and mild hyperemia. Physical examination revealed peripheral ulcerative keratitis superiorly and a salmon-colored lesion in the superior conjunctiva. Results/UNASSIGNED:The differential diagnosis of superior corneal thinning includes collagen vascular disease, Terrien's marginal degeneration, infectious keratitis, and other forms of peripheral keratitis. Our patient was diagnosed with conjunctival MALT lymphoma by surgical excision of the mass, and the peripheral ulcerative keratitis may be related to this diagnosis. Conclusion/UNASSIGNED:Although rare, this case demonstrates a peripheral keratitis possibly related to the underlying disease of MALT lymphoma. The patient is being treated with local radiation treatment.

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.

Importance/UNASSIGNED:Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD. Objective/UNASSIGNED:To determine whether metformin use is associated with reduced odds of developing AMD. Design, Setting, and Participants/UNASSIGNED:This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020. Exposures/UNASSIGNED:Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims. Main Outcomes and Measures/UNASSIGNED:Risk of developing AMD. Results/UNASSIGNED:A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]). Conclusion and Relevance/UNASSIGNED:In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.

Fuchs endothelial corneal dystrophy (FECD) is the most common posterior corneal dystrophy and the leading indication for corneal transplantation in the United States. FECD is slowly progressive, and patients develop gradual corneal endothelial decompensation, eventually resulting in failure of the endothelium to maintain corneal deturgescence. Medical management consists of topical hyperosmotic agents to facilitate dehydration of the cornea, but surgical intervention is often required to regain corneal clarity. The surgical management of FECD has evolved over the past two decades as corneal transplantation techniques have allowed for more selective keratoplasty and replacement of only the diseased layers of the cornea. Prior surgical management consisted of penetrating keratoplasty (PK) that carried significant intraoperative risks associated with "open sky" as well as postoperative risks of graft rejection, wound dehiscence, postoperative astigmatism, and prolonged visual rehabilitation. In the past 15 years, endothelial keratoplasty (EK) has become the treatment of choice for endothelial disease, significantly reducing the risks associated with the surgical treatment of FECD. Here we discuss the current surgical management of FECD, including the introduction of Descemet stripping only (DSO), and highlight future investigative efforts.

INTRODUCTION/BACKGROUND: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/CONCLUSIONS: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/BACKGROUND:ClinicalTrials.gov Identifier, NCT03525678.