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Antibody-drug conjugates (ADCs) are a fast-growing class of cancer drugs designed to selectively deliver cytotoxic payloads through antibody binding to cancer cells with high expression of the target antigen, thus reducing systemic exposure and minimizing off-target effects. However, ADCs are associated with various ocular adverse events (AEs) that may impact treatment administration and patient outcomes. In this review, we provide a summary of ocular AEs associated with approved and investigational ADCs, recommendations for the mitigation and management of ocular AEs, current guidelines and expert opinions, and recommendations for clinical practice. A literature search was performed, using PubMed and Google Scholar, for English-language articles published between January 1985 and January 2023 to identify studies reporting ocular AEs associated with ADC use. Search terms included generic and investigational names of all identified ADCs, and further searches were performed to identify strategies for managing ADC-associated ocular AEs. ADC-associated ocular AEs include symptoms such as blurred vision and foreign-body sensation and signs such as corneal fluorescein staining, corneal pseudomicrocysts, and conjunctivitis. Reported management strategies include ADC dose modification (eg, dose delay or reduction), cool compresses, artificial tears, topical vasoconstrictors, and topical steroids. Although ADC dose modification appears to be beneficial, the preventive and/or therapeutic benefits of the remaining interventions are unclear. Although the exact mechanisms are not fully understood, most ADC-associated ocular AEs are reversible with dose delay or dose reduction. Management of ocular AEs requires a multidisciplinary approach to minimize treatment discontinuation and optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To examine the effect of pharmacologic dilation on biometric parameters measured by the Lenstar LS 900, and whether these changes affect the power of the calculated intraocular lens (IOL) using multivariable formulas in an undilated versus pharmacologically dilated state. Methods: Prospective study of 98 phakic eyes from 53 patients. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and keratometry (K) readings were measured. The first set of measurements was taken prior to dilation. After dilation (pupil diameter ≥ 6.0 mm), a second set of measurements was taken. The Barrett, Olsen, Hill-RBF, Haigis, SRK/T, and Holladay I formulas were used to calculate IOL power before and after dilation. Two calculation methods were used: method A used a commonly available IOL targeted to achieve the lowest myopic spheroequivalent residual refraction; method B calculated ideal IOL power for emmetropia. Results: Statistically significant increases were seen in CCT (p < 0.01), ACD (p < 0.01), and AL (p < 0.01) whereas a statistically significant decrease was seen in LT (p < 0.01) post dilation. Using method A, the percentage of eyes which would have received an IOL with 0.5 D or 1.0 D of higher power, if post-dilation measurements were used, were 25.5%, 30.6%, 20.4%, and 23.5% for Barrett, Olsen, Hill-RBF, and Haigis, respectively. Using method B, only Haigis and Olsen had a statistically significant increase in ideal IOL power. Conclusions: Pharmacologic dilation can be associated with an increase in non-custom IOL dioptric power when using multivariable formulas, which may lead to a myopic surprise. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Purpose: To identify whether there has been a decline in ocular toxoplasmosis at a tertiary uveitis practice.Methods: Retrospective review of new patients at the University of Illinois Uveitis Service from 1973 to 2012.Results: There were 6820 patients with adequate records for inclusion; 323 (4.7%) were diagnosed with ocular toxoplasmosis. There was a 78.0% decline in prevalence of ocular toxoplasmosis from 2008 to 2012 compared with 1973 to 1977. Compared with the aggregate uveitis population, toxoplasmosis patients were more likely to be Hispanic (p<0.0001) and less likely to be African American (p<0.0001). Ocular toxoplasmosis in Hispanics commonly occurred in foreign-born patients (85.3%).Conclusions: The diagnosis of ocular toxoplasmosis at our clinic declined, with Hispanics accounting for an increasing proportion of cases. These trends are consistent with the decreasing toxoplasmosis seropositivity in the United States, but may also reflect decreased referrals due to improved management of ocular toxoplasmosis in primary clinics. [ABSTRACT FROM AUTHOR]

Posterior keratoconus (PKC) is a rare, typically non-inflammatory condition that is characterised by an abnormal posterior corneal curvature, which may be accompanied by overlying stromal opacification. It is usually congenital and can be associated with other ocular and systemic abnormalities. PKC remains a clinical diagnosis, although imaging techniques including ultrasound biomicroscopy and anterior segment optical coherence tomography may be useful tools for confirmation and classification. Genetic studies should be considered, although no specific genetic defects have been identified thus far. As a potential cause of amblyopia, early diagnosis and management are crucial in maximising visual potential. Occasionally, management considerations may also include surgical intervention, such as corneal transplantation. Intraocular lens power calculation at the time of cataract surgery requires special consideration. Here, we review the present literature on PKC and consider future directions in the management of this rare entity. [ABSTRACT FROM AUTHOR]

Slit-lamp photos of the left eye at presentation (a) and two weeks into oral miltefosine therapy (b), at which time there was an increase in conjunctival injection and new stromal infiltrates. Slit lamp examination of the left eye revealed conjunctival injection and a ring infiltrate in the cornea. A 29 year-old South Asian male presented with 4 months of fluctuating pain, photophobia, and decreased vision in his left eye. [Extracted from the article]

This JAMA Insights describes dry eye disease and summarizes its types, pathology, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center. Methods: Retrospective case series. Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn's disease. Another patient had a history of alcoholic liver cirrhosis, Crohn's disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization. Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay. [ABSTRACT FROM AUTHOR]

The presence of an elevated anti-glutamic acid decarboxylase (GAD) antibody level has been associated with a number of eye movement abnormalities as well as other findings, including cerebellar ataxia and insulin-dependent diabetes mellitus. Skew deviation in association with anti-GAD antibodies has not been previously reported. Here the authors report a case of alternating skew deviation along with cerebellar-brainstem signs in a patient with an elevated anti-GAD antibody titre. Follow-up neurologic evaluation after treatment with intravenous immunoglobulin revealed improvement in cerebellar-brainstem signs, whereas ophthalmic evaluation was stable. [ABSTRACT FROM AUTHOR]

The entry of herpes simplex virus into cells was once thought to be a general process. It is now understood that the virus is able to use multiple mechanisms for entry and spread, including the use of receptors and co-receptors that have been determined to be cell-type specific. This is certainly true for ocular cell types, which is important as the virus may use different mechanisms to gain access to multiple anatomic structures in close proximity, leading to various ocular diseases. There are some patterns that may be utilized by the virus in the eye and elsewhere, including surfing along filopodia in moving from cell to cell. There are common themes as well as intriguing differences in the entry mechanisms of herpes simplex virus into ocular cells. We discuss these issues in the context of conjunctivitis, keratitis, acute retinal necrosis, and other ocular diseases. [ABSTRACT FROM AUTHOR]