An overview of the efficacy and safety of brexpiprazole for the treatment of schizophrenia in adolescents.

INTRODUCTION: Onset of psychotic symptoms occurs prior to age 19 in 39% of patients with schizophrenia. There are limited approved treatment options for adolescents with schizophrenia. Brexpiprazole was approved by the United States Food and Drug Administration (FDA) for treatment of schizophrenia in adolescents in 2022. AREAS COVERED: Extrapolation of adult data to youth and use of pharmacologic modeling coupled with open long-term safety data were used by the FDA to approve brexpiprazole for adolescent schizophrenia. These were all reviewed herein. EXPERT OPINION: D2 receptor partial agonist antipsychotic agents are preferred in the early phase of treatment of psychotic disorders. Approval of brexpiprazole in adolescent schizophrenia provides an additional option. Brexpiprazole was approved by the FDA on the basis of extrapolation of adult data without controlled trials in adolescents. This reduces placebo exposure in young people. Two previous agents (asenapine and ziprasidone) approved for adult schizophrenia failed to separate from placebo in adolescent schizophrenia studies; this partially undermines the process of extrapolation. For brexpiprazole, the paucity of data in adolescents relegates it to second-line agent. More research on brexpiprazole is needed to delineate its relative role in the management of adolescent schizophrenia.

Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory.

Introduction: Separate unimodal magnetic resonance imaging (MRI) literatures have shown that hippocampal gray matter macrostructure (volume) and microstructure (diffusion) decline with age and relate to episodic memory performance, with multimodal MRI studies reporting that episodic memory may be better explained by a combination of these metrics. However, these effects are often assessed independent of age or only within older adults and therefore do not address whether these distinct modalities explain variance in (i.e, mediate) the effect of age on episodic memory. Methods: Here, we simultaneously examined the unique and joint contribution of hippocampal volume and diffusion to age-related differences in episodic memory in 83 younger and 61 older adults who underwent a T1- and diffusion-weighted MRI and completed the Rey Auditory Verbal Learning Test. Results: As expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that the structural metrics did not jointly mediate the age-memory relationship. Discussion: Together, these findings indicate that hippocampal microstructure uniquely contributes to age-related differences in episodic memory and suggest that volume and diffusion capture distinct neurobiological properties of hippocampal gray matter.

Rapidly progressive streptococcus dysgalactiae corneal ulceration associated with erlotinib use in stage IV lung cancer.

PURPOSE: To present a unique case of streptococcus dysgalactiae keratitis with progression to corneal perforation and endophthalmitis, in the setting of epidermal growth factor receptor inhibitor (erlotinib) therapy for advanced non-small cell lung cancer. OBSERVATIONS: An 89-year-old female with non-small cell lung cancer on erlotinib presented with corneal perforation due to infectious keratitis. Microbial cultures grew streptococcus dysgalactiae, a virulent pathogen known to affect immunocompromised patients that has not been previously described to cause infectious keratitis. Despite aggressive medical intervention, the clinical course was complicated by rapid progression to no light perception visual acuity in the setting of endophthalmitis with orbital cellulitis, necessitating evisceration. CONCLUSIONS AND IMPORTANCE: Epidermal growth factor receptor inhibitor therapy can result in significant ocular complications including dry eyes, epithelial keratopathy, non-healing abrasions, infectious keratitis, and rarely, corneal melting and perforation. These side effects can predispose patients to aggressive infections with rare organisms, highlighting the importance of understanding the ocular side effects of systemic chemotherapeutic agents.

A Convergence of Ophthalmic and Life-threatening Emergencies: Acute Angle Closure Glaucoma and Subarachnoid Hemorrhage.

PURPOSE: To report a unique case of acute angle closure glaucoma in the setting of a subarachnoid hemorrhage due to a ruptured cerebral aneurysm. MATERIALS AND METHODS: Observational case report and review of the literature. RESULTS: A 75-year-old woman presented with blurry vision, nausea, vomiting, and left eye pain. She was found to have a complete third nerve palsy, with ptosis, exotropia, hypotropia, and a fixed mydriasis with resultant acute angle closure glaucoma. Pilocarpine was initiated, and neuroimaging revealed a subarachnoid hemorrhage from a ruptured posterior communicating artery aneurysm. The aneurysm was successfully coiled, and outpatient laser iridotomies were subsequently performed. Only 4 prior cases of acute angle closure glaucoma in the setting of a third nerve palsy have been reported in the literature. To our knowledge, this case is the first report of angle closure glaucoma in the setting of a subarachnoid hemorrhage. CONCLUSIONS: This case of a complete third nerve palsy in the setting of a subarachnoid hemorrhage leading to acute angle closure highlights the importance of ruling out this life-threatening diagnosis when neurological signs of increased intracranial pressure and cranial nerve palsies are present.

Treatment Limitations With PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem): One Centers Experience.

OBJECTIVES: The prosthetic replacement of the ocular surface ecosystem (PROSE) device is used to treat difficult-to-manage ocular surface disease (OSD) and ectasia. Previous studies have demonstrated positive treatment outcomes. This study aims to document treatment failures to better tailor treatment and address limitations with its use. METHODS: Retrospective chart review of consecutive PROSE fits performed at Northwell Health from 2012 to 2016. Reasons for patient discontinuation of treatment were documented, and potential risk factors for treatment failure were assessed. RESULTS: The total number of eyes treated was 125. Fifty five eyes had ectasia, 67 had OSD, and 3 had both ectasia and OSD. A total of 8/125 (6.4%) of eyes failed treatment; 6/8 (75%) of failed treatments had worsening corneal edema, all of which had presumed risk factors for lower endothelial cell counts. Two eyes discontinued use secondary to intractable debris on the device, blurring vision. The most common diseases in patients failing therapy in descending order included: keratoconus and Fuch's dystrophy, ectasia after penetrating keratoplasty, and graft versus host disease. Those with presumed risks factors for lower endothelial cell counts (Fuch's dystrophy and patients with previous penetrating keratoplasty) were more likely to fail (22.2%) compared with those without a risk of a low endothelial cell count (1.6%). CONCLUSION: Although PROSE use has high success, corneal edema secondary to endothelial dysfunction is a potential limitation that may lead to treatment failure. Patients with lower endothelial cell counts after penetrating keratoplasty or with Fuch's dystrophy were more likely to fail treatment.