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A care algorithm for partial globe subluxation cases with optic nerve and at least one extraocular muscle (EOM) transection is presented after a literature review was performed using key term variations of globe, ocular, subluxation, optic nerve evulsion or transection, and trauma. Partial globe subluxation cases with transection of the optic nerve and at least 1 EOM were included. Exclusion criteria included globe rupture, complete enucleation defined by a globe without at least 1 EOM attachment, or unclear details confirming optic nerve transection. Including the patient presented herein, a total of 24 patients with 26 eyes were analyzed. About 73.08% of cases underwent initial repositioning (n = 19), with 11.54% of those requiring secondary enucleation or evisceration (n = 3). Of the secondarily managed cases, 2 of the 3 cases listed pain (n = 2) and inadequate cosmesis (n = 1) as rationale. We found that 26.92% of cases underwent initial enucleation (n = 7), citing lack of visual potential and limiting later complications. Most cases favored repositioning, which was typically sustainable. Initial repositioning can improve cosmetic outcome and psychological impact. Given the low risk of later management, cases of traumatic partial subluxation with EOM and optic nerve transections should attempt initial repositioning. [ABSTRACT FROM AUTHOR]

Hypoxia‐inducible factor (HIF) plays a critical role in the mechanisms that allow cells to adapt to various oxygen levels in the environment. Specifically, HIF‐1⍺ has shown to be widely involved in cellular repair, survival, and energy metabolism. HIF‐1⍺ has also been found in increased levels in cancer cells, highlighting the importance of balance in the hypoxic response. Promoting HIF‐1⍺ activity as a potential therapy for degenerative diseases and inhibiting HIF‐1⍺ as a therapy for pathologies with overactive cell proliferation are actively being explored. Digoxin and metformin, HIF‐1⍺ inhibitors, and deferoxamine and ⍺‐ketoglutarate analogues, HIF‐1⍺ activators, are being studied for application in age‐related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, these same medications have retinal toxicities that must be assessed before implementation of therapeutic care. Herein, we highlight the duality of therapeutic and toxic potential of HIF‐1⍺ that must be carefully assessed prior to its clinical application in retinal disorders. [ABSTRACT FROM AUTHOR]

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert–Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype–phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype–phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed. [ABSTRACT FROM AUTHOR]

RPGR mutations are the most common cause of X-linked retinitis pigmentosa (XLRP). High myopia has been described as a very frequent feature among affected female carriers of XLRP. However, the clinical phenotype of female patients presenting with X-linked RPGR-related high myopia has not been well described. Retrospective case series of four female patients with RPGR mutations and a diagnosis of high myopia, who presented to two academic eye centers. Clinical data, including age, family history, visual acuity, refractive error, dilated fundus exam, fundus photography, optical coherence tomography, electroretinography, and results of genetic testing, were collected. Three RPGR variants identified in the present study have not been previously associated with myopia in female carriers. One variant (c.2405_2406delAG, p.Glu802Glyfs *32) has been previously associated with a myopic phenotype in a female patient. Patients became symptomatic between the first and sixth decades of life. Myopia-associated tilted optic discs and posterior staphyloma were present in all patients. Two patients presented with intraretinal migration of the retinal pigment epithelium. RPGR-related high myopia has been associated with mutations in exons 1–14 and ORF15 in heterozygous females. There is a wide range of visual function among carriers. Although the exact mechanism of RPGR-related high myopia is still unclear, continued molecular diagnosis and description of phenotypes remain a crucial step in understanding the impact of RPGR mutations on visual function in female XLRP carriers. [ABSTRACT FROM AUTHOR]

Introduction: Leber congenital amaurosis (LCA) type 2, due to disease‐causing variants in RPE65, is characterized by severe visual loss in early infancy. Current treatments include voretigene neparvovec‐rzyl (VN) for RPE65‐associated LCA. Herein, we present the long‐term follow‐up of a patient treated with VN using quantitative autofluorescence (488 nm excitation). Case Report: A 9‐year‐old girl with a diagnosis of LCA with biallelic variants in RPE65 presented for evaluation. The patient underwent VN treatment at the age of 11. The patient returned to clinic at age of 19 at which time imaging revealed evidence of chorioretinal atrophy. Quantitative autofluorescence performed prior to gene therapy and at 6‐ and 8‐year follow‐up revealed a central area of fundus autofluorescence. Discussion This case report demonstrates acquisition of fundus autofluorescence at 6‐ and 8‐year follow‐up despite the development of chorioretinal atrophy. [ABSTRACT FROM AUTHOR]

Bietti crystalline dystrophy (BCD) is an ultra-rare orphan disorder that can lead to blindness. Because of the variable rates of progression of the disease, it is necessary to identify suitable outcome measurements for tracking progression in BCD. A retrospective analysis of patients with a clinical and genetic diagnosis of BCD was conducted. Four measurements of spectral domain-optical coherence tomography were compared to patients' best corrected visual acuity. We observed that patients with higher measurements of foveolar thickness, choroidal thickness in the foveolar region, ellipsoid zone band length and the outer nuclear layer + area, had on average better visual acuity. Future studies are needed to validate the structural–functional correlations we observed in BCD and to propose a sensitive and clinically meaningful outcome measurement for tracking this rare, variable disease. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population. [ABSTRACT FROM AUTHOR]