Celebi ARC, Park EA, Verticchio Vercellin AC, Tsikata E, Lee R, Shieh E, Antar H, Freeman M, Zhang J, Que C, Simavli H, McClurkin M, Guo R, Elze T, de Boer JF, Chen TC.
Structure-Function Mapping Using a Three-Dimensional Neuroretinal Rim Parameter Derived From Spectral Domain Optical Coherence Tomography Volume Scans. Transl Vis Sci Technol 2021;10(6):28.
AbstractPurpose: To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods: Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results: The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions: Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.
Chodnicki KD, Prasad S.
Ophthalmic Implications of Chimeric Antigen Receptor T-Cell Therapy. Semin Ophthalmol 2021;36(4):329-334.
AbstractChimeric antigen receptor (CAR) T-cell therapy is a revolutionary addition to the burgeoning field of immunotherapy. CAR T-cells are engineered by combining a T-cell receptor with the antigen-binding site of an immunoglobulin that allows the hybrid cell to target antigens of interest. CAR T-cell therapy has been approved to treat various hematologic malignancies, including relapsed or refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. While the treatment efficacy is exciting, challenges remain in understanding the unique spectrum of adverse effects of CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. Innovative research is underway to expand this therapy into solid tumors and fields beyond hematology and oncology. To date, there has been limited research into ophthalmic uses and considerations of CAR T-cell therapy. This review focuses on preclinical investigations into CAR T-cell therapy for retinoblastoma and uveal melanoma, as well as ophthalmic complications of CAR T-cell therapy.
Chwalisz BK.
Cerebral amyloid angiopathy and related inflammatory disorders. J Neurol Sci 2021;424:117425.
AbstractInflammatory cerebral amyloid angiopathy is a largely reversible inflammatory vasculopathy that develops in an acute or subacute fashion in reaction to amyloid protein deposition in the central nervous system blood vessels. There are two recognized pathologically characterized variants: cerebral amyloid angiopathy-related inflammation (CAAri) and A beta-related angiitis (ABRA). Both variants produce a clinical picture that resembles primary angiitis of the CNS but is distinguished by a characteristic radiologic appearance. Although originally defined as a clinicopathologic diagnosis, it can now often be diagnosed based on clinicoradiologic criteria, though confirmation with brain and meningeal biopsy is still required in some cases. This disorder typically responds to steroids but addition of other immune suppressants may be needed in some cases to control the disease.
Ciociola EC, Kavitha S, Sengupta S, Wiggs JL, Kader MA, Raman GV, Rajendrababu S, Ramulu PY, Venkatesh R, Zebardast N.
The Heritability of Primary Angle Closure Anatomic Traits and Predictors of Angle Closure in South Indian Siblings. Am J Ophthalmol 2021;
AbstractPURPOSE: To estimate the heritability of ocular biometric and anterior chamber morphologic parameters and to determine predictors of angle closure concordance in South Indian probands with angle closure and their siblings. DESIGN: Prospective observational cohort study. METHODS: Subjects received a standardized ophthalmic examination, A-scan ultrasonography, pachymetry, and anterior segment optical coherence tomography (ASOCT) imaging. Heritability was calculated using residual correlation coefficients adjusted for age, sex, and home setting. Concordant siblings pairs were defined as both proband and sibling with angle closure. Predictors of angle closure concordance among siblings were calculated using multivariable logistic regression models. RESULTS: 345 sibling pairs participated. All anterior chamber parameters were highly heritable (p<0.001 for all). Similarly, all iris parameters, axial length, lens thickness (LT), central corneal thickness, anterior lens curvature, lens vault (LV), spherical equivalent, and intraocular pressure were moderately to highly heritable (p<0.004 for all). LV and LT were more heritable among concordant siblings (p<0.05 for both). In contrast, ASOCT angle parameters had statistically insignificant heritability estimates. In multivariable analyses, siblings older than their probands were more likely to be concordant for angle closure (OR=1.05 (95% CI 1.01, 1.09), p=0.02) and siblings with deeper anterior chamber depths (ACD) compared to their proband were less likely to be concordant for angle closure (OR=0.74 (95% CI 0.64, 0.86), p<0.001). CONCLUSIONS: Iris, anterior chamber, and lens parameters may be heritable while angle parameters were not. LT and LV may play important roles in the pathogenesis of angle closure. Siblings who are older or have a shallower ACD may need more careful disease monitoring.
Cohen DA, Gise R, Gaier ED.
Serum Biomarkers in Neuro-Ophthalmology: When to Test. Semin Ophthalmol 2021;36(4):322-328.
AbstractDiscovery and characterization of serologic biomarkers has revolutionized the diagnostic framework of systemic and paraneoplastic autoimmune neuro-ophthalmic diseases. Expanding recognition of the multiple ocular and visual manifestations of these conditions highlights the important role of the referring provider in identifying potential cases. Increasing ease of access to serologic testing also enables these practitioners to initiate the diagnostic work-up in suspected cases. We aimed to provide an update on the current knowledge surrounding and use of relevant autoimmune biomarkers by correlating specific clinical neuro-ophthalmic manifestations with autoantibody biomarkers. The utility of select biomarkers for myasthenia gravis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein-IgG-associated disorder, opsoclonus-myoclonus syndrome, anti-collapsin-response mediator protein-5 optic neuropathy, and glial fibrillary acidic protein-IgG-associated disease are discussed with particular focus on the clinical contexts in which to consider testing.
Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW, and Consortium UKBEV, and Consortium UKBEV, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong J-S, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, Macgregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, Khawaja AP.
Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images. PLoS Genet 2021;17(5):e1009497.
AbstractOptical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.