Astigmatism Management in Modern Cataract Surgery.

Astigmatism management is a frequently encountered challenge in the world of modern cataract surgery. This review article investigates the importance of astigmatic correction and seeks to uncover the critical components of preoperative evaluation. With the rapid growth of new technologies and techniques, this article aims to also catalogue and clarify the multitude of astigmatism treatment options available for the cataract surgeon.

Qualitative use of ICG angiography and lymphography in periorbital surgery.

PURPOSE: Open imaging fluorescence devices have been utilized in surgical oncology, vascular and plastic surgery; however, the role of indocyanine green (ICG) in periorbital surgery and lymphatics has not been explored. METHODS: A prospective, single-center diagnostic study was conducted from 2021 to 2022 utilizing ICG to assess both the periorbital vasculature and lymphatics. Fluorescence was captured with open-imaging fluorescent devices. For ICG angiography, a total of 5-10 mg of ICG was given intravenously at various time points to visualize intraoperative blood flow to eyelid flaps, vascular tumors, or extraocular muscles. For ICG lymphography, 0.03-0.06 mg of ICG was injected subcutaneously to visualize the periorbital and facial lymphatic drainage. RESULTS: Twenty-two patients underwent ICG angiography. Periorbital vascular supply was seen in eyelid reconstructions (n = 8), anophthalmic reconstructions (n = 2), lacrimal gland tumors (n = 2), orbital venous malformations (n = 2), tumor metastasis (n = 1) and benign tumors (n = 1). The anterior ciliary arteries were visualized to the extraocular muscles in fracture repairs (n = 3) and muscle biopsies (n = 2). Ten patients underwent ICG lymphangiography highlighting the global periorbital lymphatic system. CONCLUSION: ICG allows for visualization of the vasculature of extraocular muscles and tumors, assessing perfusion of flaps during reconstruction and the global periorbital lymphatic drainage pathways.

Globe Compression by Bone Fragments in Orbital Blow-in Fractures: A Case Series and Systematic Review.

PURPOSE: The purpose of this study was to describe the clinical characteristics, management, and outcomes of orbital blow-in fractures involving compression of the globe by bone fragments. METHODS: A retrospective case series and systematic literature review were performed. RESULTS: Three male patients (mean age 29 years) with orbital blow-in fractures causing globe indentation presented with extraocular movement restriction, choroidal folds, and B-scan ultrasonography demonstrating deformation of the globe contour by a hyperechoic bone fragment. All underwent surgical repair within 1 day of presentation resulting in improved visual outcomes. An additional 10 cases were identified in the literature review. The majority of patients were male (80%) with a mean age of 29 years. Fractures originated primarily from the lateral orbital wall (50%) or the orbital roof (40%). Globe compression was evident on CT of the orbit (100%) and ultrasonography (30%). Common presenting signs included decreased visual acuity (70%), restriction of supraduction (40%) or abduction (40%), choroidal folds (30%), brow laceration (40%), periorbital edema (40%), and hypoglobus (40%). Most patients underwent surgical intervention (80%) involving fracture reduction (50%) or fragment removal (38%). Reported postsurgical outcomes were excellent with resolution of diplopia, motility, and visual acuity. CONCLUSION: Globe indentation from blow-in fractures are rare. Clinicians should be suspicious in cases of high-velocity trauma to the superolateral orbit with hypoglobus, motility limitation, and indentation of the globe upon dilated exam. Prompt diagnosis and early surgical removal of the compressive orbital bone fragments in a multidisciplinary fashion can lead to good visual, functional, and cosmetic outcomes.

A review of surgical management of progressive myogenic ptosis.

PURPOSE: Surgical correction of myogenic ptosis is a sophisticated endeavor, as the disease is progressive and the post-operative course is prone to significant complications. We sought to review the literature for repair techniques in different types of myogenic ptosis. METHODS: A PubMed/MEDLINE literature search of publications pertaining to surgical outcomes of progressive myogenic ptosis repair was performed. Studies included were original retrospective studies with a minimum of four patients. RESULTS: A total of 27 articles were identified and divided by etiology of myogenic ptosis; either chronic progressive external ophthalmoplegia (CPEO), oculopharyngeal muscular dystrophy (OPMD), myasthenia gravis (MG), or mixed. Surgical techniques predominantly involved levator advancement, levator resection, frontalis sling, blepharoplasty, and Fasanella-Servat. Success rates ranged from 60.5% to 100%. Significant postoperative complications included ptosis recurrence, under-correction, over-correction, keratopathy, lagophthalmos, sling exposure, and sling infection. CONCLUSION: Like surgical repair for other forms of ptosis, correction of progressive myogenic ptosis is guided by levator excursion. However, myogenic ptosis is especially challenging as it is characterized by worsening ptosis and the loss of protective corneal mechanisms. The goals of care with myogenic ptosis involves repairing ptosis just sufficiently to alleviate visual obstruction while avoiding adverse post-operative complications. This intentional under-correction subsequently increases susceptibility for ptosis recurrence. Myogenic ptosis repair therefore requires delicate balancing between function, sustained repair, and corneal protection.

Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.

Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer's disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.

Ocular surface disease associated with immune checkpoint inhibitor therapy.

Immune-related adverse events (irAEs) is a term used to describe the various toxicities associated with immune checkpoint inhibitor (ICI) use. As this class of cancer immunotherapy grows, the diversity of documented irAEs also continues to expand. Ocular toxicities secondary to ICI use are relatively rare, with dry eye and uveitis as the most frequently reported ocular side effects. This article specifically investigates the relationship between ocular surface disease and ICI therapy through a review of the existing literature. Dry eye disease (DED), conjunctivitis, and keratitis were the most commonly reported irAEs affecting the ocular surface across the 29 studies reviewed. Keratoplasty graft rejection was also described in two case reports. Our review of eight clinical trials found the incidence of DED, the most common ocular surface irAE, to range from 1 to 4%. Nearly all cases of ocular surface irAEs were graded as mild or moderate in severity and were often self-limited or controlled with conservative treatment. Duration of checkpoint inhibitor use prior to onset of ocular surface side effects varied widely, ranging from days to months. Ocular surface toxicities associated with checkpoint immunotherapy appear to be under-reported and under-investigated. Further work remains to be done to investigate the full breadth of ocular surface pathologies and the molecular mechanisms by which these toxicities occur.

The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain.

We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TADcPcdh) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression. Genes encoding stochastically expressed protocadherins were transcribed by increased numbers of cortical neurons, indicating relaxation of single-cell constraint. SETDB1-dependent loop formations bypassed 0.2-1 Mb of linear genome and radiated from the TADcPcdh fringes toward cis-regulatory sequences within the cPcdh locus, counterbalanced shorter-range facilitative promoter-enhancer contacts and carried loop-bound polymorphisms that were associated with genetic risk for schizophrenia. We show that the SETDB1 repressor complex, which involves multiple KRAB zinc finger proteins, shields neuronal genomes from excess CTCF binding and is critically required for structural maintenance of TADcPcdh.