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.

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.

An unusual case of idiopathic calcinosis of the eyelid.

Idiopathic subepidermal calcinosis, also known as idiopathic calcinosis cutis, is a rare condition, which typically presents as a small, hard, subepithelial mass in the absence of systemic disease and trauma. We report on an atypical case of idiopathic calcinosis, which appeared in an otherwise healthy 61-year-old female along the tarsus of her right upper eyelid. The purpose of this case report is to demonstrate idiopathic calcinosis in an unusual location that is deep to the dermis and to discuss the vast differential diagnosis of this entity.

Long Term Temporal Changes in Structure and Function of Rat Visual System After Blast Exposure.

Purpose: We identify long-term ocular sequelae subsequent to experimental blast exposure. Methods: Male Long-Evans rats were exposed to 230 kPa side-on primary blast overpressure using a compressed air driven shock tube. Visual system function and structure were assessed for 8 weeks after exposure using optokinetic nystagmus and optical coherence tomography. Vitreous protein expression and histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was recorded bilaterally during blast in a subset of animals. Results: Blast pressure profiles resembled the Friedlander waveform indicative of an open field blast. Peak IOP in directly-exposed eyes (240 kPa) was similar to peak blast overpressure, but IOP in indirectly-exposed eyes was 30% lower. Contrast sensitivity of blast-exposed animals decreased significantly by 20% 1 day after blast and did not recover by 8 weeks. Significant swelling and structural damage to the corneal epithelial and stromal layers were observed 2 weeks after blast exposure. Swollen corneas increased 254 ± 143 µm from baseline by 6 weeks, and scarring developed by 8 weeks. Histology revealed additional lens pathology 1 week after blast, suggestive of cataract development. Endothelial cell density increased significantly in blast-exposed animals between 1 and 4 weeks. Neurofilament heavy chain significantly increased after blast and returned to near baseline values by 8 weeks. Inflammatory cytokine changes corroborated ocular pathology findings. Conclusions: These data demonstrate immediate visual dysfunction and biochemical responses, but delayed structural pathology, in response to single primary blast exposure. The delayed pathology time course may provide a window to implement treatment strategies for improved visual outcome.

EZOGABINE (POTIGA) MACULOPATHY.

PURPOSE: To present a case of partially reversible retinal toxicity related to a newer epilepsy medication, ezogabine (Potiga). METHODS: Case report with multimodal imaging. PATIENT: A patient presented 9 months after starting ezogabine for a screening eye examination with new retinal pigment abnormalities in the maculas of both eyes. RESULTS: These macular abnormalities are characterized for the first time with multimodal imaging. They were partially reversible after cessation of the drug. CONCLUSION: Ezogabine toxicity presents as pigmentary changes in the macula on fundus examination and has newly described characteristics on imaging that can guide ophthalmologists when they perform the FDA-recommended 6-month screening visits for ocular toxicity.

Undifferentiated Nonrhabdomyosarcoma Soft Tissue Sarcoma of the Orbit.

A 6-month-old boy presented with recurrent, poorly differentiated orbital sarcoma diagnosed as nonrhabdomyosarcoma soft tissue sarcoma, as pathologic and immunohistochemical evaluation was inconsistent with rhabdomyosarcoma or other specific sarcoma subtypes. He responded favorably to a treatment regimen for poorly differentiated sarcomas.

Impact of micropulsed ultrasound power settings on the efficiency and chatter associated with lens-fragment removal.

PURPOSE: To determine the optimum power settings in micropulsed ultrasound (US). SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Pig lenses hardened to be comparable to dense human cataracts were cut into 2.0 mm cubes and removed using micropulsed longitudinal US with previously optimized settings (6 milliseconds on and 6 milliseconds off and using a 0.9 mm 30-degree beveled bent phaco tip). The aspiration was set at 40 mL/min and the vacuum level at 550 mm Hg. Twenty lens cubes were tested with the power set from 10% to 100% in increments of 10%. Primary outcome measures were efficiency time (time to lens removal) and chatter (number of times the lens fragment visibly bounced off the tip). RESULTS: Efficiency time decreased with increasing power. There was a correlation between power and efficiency time (R(2) = 0.41, P = .046), which was more substantial between 30% and 100% power (R(2) = 0.71, P = .004). The mean number of chatter events did not differ significantly between power settings (R(2) = 0.012, P = .1195). CONCLUSIONS: There was a 5-fold increase in efficiency between 10% power and 20% power, which likely indicates that there is a minimum power threshold for efficient breakup of the lens. Between 20% and 100% power, there was a linear, strong, and statistically significant improvement in efficiency in these lens fragments. In addition, with micropulsed US there was little chatter or microchatter throughout the power range. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Porcine lens nuclei as a model for comparison of 3 ultrasound modalities regarding efficiency and chatter.

PURPOSE: To validate a porcine lens model by comparing density and ultrasound (US) with known human standards using the Infiniti Ozil with Intelligent Phacoemulsification (torsional), Whitestar Signature Micropulse (longitudinal), and Ellips FX (transversal) modalities. SETTING: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Lens nuclei were formalin soaked in hour-based intervals and divided into 2.0 mm cubes. Density was characterized by crushing experiments and compared with known human measures. Efficiency and chatter were examined. RESULTS: The mean weight to cut thickness in half ranged from 16.9 g ± 5.5 (SD) in the 0-hour group to 121.3 ± 47.5 gm in the 4-hour group. Lenses in the 2-hour group (mean 70.2 ± 19.1 g) best matched human density (P=.215). The mean efficiency ranged from 0.432 ± 0.178 seconds to 9.111 ± 2.925 seconds; chatter ranged from zero to 1.85 ± 1.927 bounces. No significant difference was detected when comparing the 2-hour formalin group with human lenses in torsional and transversal US. There was no significant difference between transversal and torsional modalities, consistent with human studies. Although longitudinal (6 milliseconds on, 12 milliseconds off) was significantly more efficient at 50% power than at 25%, there was no significant difference compared with transversal or torsional US. CONCLUSIONS: Animal lenses soaked for 2 hours in formalin were most comparable to human lenses. Longitudinal US may be an acceptable alternative to torsional and transversal US.

Objective comparison of 4 nonlongitudinal ultrasound modalities regarding efficiency and chatter.

PURPOSE: To compare efficiency and chatter of Infiniti Ozil with and without Intelligent Phacoemulsification (IP) and the Signature Ellips with and without FX. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Brunescent 2.0 mm human lens cubes were created by an instrument devised for this study. Cubes were tested (10 per test) for time of particle removal (efficiency) and for the number of times the lens particle bounced off the tip (chatter) at 300 mm Hg and 550 mm Hg, 50% and 100% power, and 50% and 100% amplitudes (amplitude for Ozil only). RESULTS: Of the ultrasound settings, efficiency varied from a mean of 3.3 seconds ± 1.4 (SD) to 50.4 ± 11.7 seconds and chatter from 0.0 to 52.0 ± 16.7 bounces per run. The Ozil-IP was generally more efficient than the Ozil and the Ellips FX more efficient than the Ellips. At optimized values, the Ozil-IP and Ellips-FX were similar. In general, efficiency and chatter were better at 550 mm Hg and at 50% power. The amplitude effect was complex. Efficiency closely correlated with chatter (Pearson r(2) = .31, P<.0001). CONCLUSIONS: Objective comparison of phacoemulsification efficiency and chatter found that optimized Ozil-IP and Ellips-FX were similar in both parameters and in general, both performed better than preceding technology. The study parameters can significantly affect efficiency and chatter, which strongly correlate with each other.

Clinical and histopathologic evaluation of six human eyes implanted with the bag-in-the-lens.

PURPOSE: To describe the clinical and histopathologic features of eyes implanted with the bag-in-the-lens (BIL), which involves the use of a twin capsulorhexis lens design, and performance of anterior and posterior capsulorhexes. DESIGN: Case series with clinicopathologic correlation. PARTICIPANTS: Six eyes implanted with the foldable, hydrophilic acrylic BIL, obtained postmortem at different postoperative times, from 4 patients were studied. METHODS: On the patients' death, the eyes were enucleated, immersed in fixative, and submitted for analyses under a high-frequency ultrasound unit (Artemis, Ultralink, St. Petersburg, FL; 50 MHz), gross analyses, and histopathologic analyses. Clinical data in each case were obtained by chart review. MAIN OUTCOME MEASURES: Clinical data obtained included patient demographics, preoperative evaluation, description of surgical implantation procedure, and postoperative outcomes. The postmortem evaluation included analyses of lens fixation and centration, as well as gross and histopathologic analyses of postoperative capsular bag opacification. RESULTS: The patients were aged 74.6+/-12.6 years at implantation. The postoperative time in this series ranged from 4 to 39 months. In all eyes for which the surgical implantation was uneventful (N = 5), postoperative BIL decentration was insignificant. In 1 eye, the anterior capsulorhexis was torn off, and although BIL implantation was still possible, a relative lens decentration was observed postoperatively, but without clinical significance. Although progressively larger amounts of Soemmering's ring formation were observed in the specimens with larger follow-up, the central area delimitated by the rhexis openings remained perfectly clear in all 6 eyes. CONCLUSIONS: This is the first series of human eyes implanted with the BIL, obtained postmortem at different postoperative times. BIL centration depends on the performance of centered capsulorhexes of appropriate size. The results confirm the concept of the lens design in that any proliferative/regenerative material remains confined to the intercapsular space of the capsular bag remnant outside the optic rim. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Comparison of the corneal endothelial protective effects of Healon-D and Viscoat.

BACKGROUND: The use of dispersive ophthalmic viscosurgical devices (OVDs) has been shown to provide significant protection against air bubble damage to the corneal endothelium when compared with cohesive OVDs. We compared the corneal endothelial protective effects of a new dispersive OVD, Healon-D, with Viscoat. METHODS: Healon-D and Viscoat were used in a randomized and masked fashion in the anterior chamber of 40 rabbit eyes during a procedure where ultrasound at 70% continuous energy was delivered for 2 min. Two millilitres of air bubbles were injected into the anterior chamber during the first minute of the procedure on each eye. Corneas were then stained with trypan blue and alizarin red and evaluated via light microscopy for endothelial injury. Both denuding of the endothelial layer, as well as damage to endothelial cells were quantified by using the Evaluation of Posterior Capsule Opacification digital imaging system. RESULTS: The denuded area for eyes treated with Healon-D and Viscoat were not significantly different (medians of 0.004167and 0.003333, respectively, P = 0.8908). There was no significant difference in the area of endothelial cell damaged (medians of 0.02183 and 0.01433, respectively, P = 0.4565). When the denuded and damaged areas were calculated together, there was also no difference in the total injured area (medians of 0.05817 and 0.05821, respectively, P = 0.5740). CONCLUSION: The new dispersive OVD Healon-D is equally as effective as Viscoat in protecting the corneal endothelial layer from denuding and damage from air bubbles during anterior segment surgery.