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Rossato FA, Su Y, Mackey A, Ng YSE. Fibrotic Changes and Endothelial-to-Mesenchymal Transition Promoted by VEGFR2 Antagonism Alter the Therapeutic Effects of VEGFA Pathway Blockage in a Mouse Model of Choroidal Neovascularization. Cells 2020;9(9)Abstract
Many patients with wet age-related macular degeneration do not respond well to anti- vascular endothelial growth factor A (VEGFA) therapy for choroidal neovascularization (CNV), and the efficacy of anti-VEGFA decreases over time. We investigated the hypothesis that fibrotic changes, in particular via endothelial-to-mesenchymal transition (EndoMT), play a role in CNV and alter the therapeutic effects of VEGFA pathway blockage. Induction of EndoMT of primary human retinal endothelial cells led to a significantly reduced response to VEGFA at the level of gene expression, cellular proliferation, migration, and tube formation. Suppression of EndoMT restored cell responsiveness to VEGFA. In a mouse model of spontaneous CNV, fibrotic changes and EndoMT persisted as the CNV lesions became more established over time. VEGFA receptor-2 (VEGFR2) antagonism further induced fibrosis and EndoMT in the CNV. The combination of VEGFR2 antagonism and fibrosis/EndoMT inhibition was more effective than either individual treatment in reducing CNV. Our data indicate that fibrosis and EndoMT are involved in the progression of CNV, are exacerbated by VEGFR2 inhibition, and could provide an explanation for the reduced efficacy of anti-VEGFA treatment over time.
Jakobiec FA, Barrantes PC, Yonekawa Y, Lad EM, Proia AD. Subretinal Mononuclear Cells in Coats' Disease Studied with RPE65 and CD163: Evidence for Histiocytoid Pigment Epithelial Cells. Am J Ophthalmol 2020;Abstract
PURPOSE: To evaluate the mononuclear cells in the subretinal exudate in Coats' disease. DESIGN: Retrospective case series. METHODS: Five enucleated globes and one cytology sample with Coats' disease and one case of chronic retinal detachment following repair of an open globe injury were examined immunohistochemically to identify the intraretinal and subretinal exudative cells. The two biomarkers were RPE65 for retinal pigment epithelium and CD163 for histiocytes, each tagged with different chromogens, yellow for pigment epithelium and purple for CD163+ monocytes/histiocytes. Expressions were sought of both biomarkers together or singly. A color shift to red in the cells' chromogenic reaction indicated the simultaneous presence of the two biomarkers. RESULTS: The majority of the mononuclear cells in Coats' disease were CD163 (purple) positive, and a minority were RPE65 (yellow) positive. An intermediate number of cells were RPE65/CD163 positive (orange-red). The eye with a chronic retinal detachment had an equal distribution of CD163 positive and RPE65/CD163 positive cells. CONCLUSIONS: The retinal pigment epithelium has several well-delineated phenotypes and functions. In normal visual physiology, the pigment epithelium supports the photoreceptors and participates in their renewal by phagocytosis of the tips of the photoreceptors. The expression of CD163, a feature of hematopoietically derived monocytes, together with RPE65 in the retinal pigment epithelium, supports differentiation toward histiocytes. Yellow staining detached pigment epithelial cells were rare. The presence of histiocytoid pigment epithelium at the level of Bruch's membrane probably also has implications for macular degeneration.
Maleki A, Gomez S, Asgari S, Bosenberg Z, Manhapra A, Walsh M, Weng A, Tseng C, He C, Anesi SD, Foster SC. Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis. Ocul Immunol Inflamm 2020;:1-6.Abstract
PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant ( = .015, = .000, = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, < .001), Age (OR = 0.95, = .03) and number of flare-ups (OR = 2.9, = .02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.
Lužnik Z, Sun Z, Nakagawa H, Taylor AW, Jurkunas UV, Yin J, Dana R. Association of α-Melanocyte-Stimulating Hormone With Corneal Endothelial Cell Survival During Oxidative Stress and Inflammation-Induced Cell Loss in Donor Tissue. JAMA Ophthalmol 2020;Abstract
Importance: Corneal endothelial cell (CEnC) damage and loss are major issues in eye banking and transplantation. The underlying mechanisms for CEnC loss are incompletely understood, and cytoprotective strategies that enhance CEnC viability could have a major effect on donor tissue quality and graft survival. Objective: To investigate the cytoprotective role of neuropeptide α-melanocyte-stimulating hormone (α-MSH) in preventing CEnC loss in eye bank cold-stored corneas under oxidative and inflammatory cytokine-induced stress. Design, Setting, and Participants: This single-center comparative research study conducted ex vivo experiments using 16 pairs of research-grade human donor corneas (courtesy of Eversight Eye Bank). Data were collected from June 2018 to November 2019, and data were analyzed from December 2019 to January 2020. Exposures: Two corneas from the same donor were randomized to either control or 0.1 mmol/L of α-MSH treatment and then subjected to oxidative stress (1.4 mmol/L of hydrogen peroxide-phosphate-buffered saline for 15 minutes at 37 °C; n = 8 pairs) or cytokine-induced stress (100 ng/mL of tumor necrosis factor-α and 100 ng/mL of interferon γ for 18 hours at 37 °C; n = 8 pairs). Corneas were then stored at 4 °C. Specular images were taken at baseline and repeated twice per week using a calibrated wide-field specular microscope. CEnC viability was assessed using a fluorescent live/dead viability assay. Main Outcome and Measures: Endothelial morphometry analysis, central corneal thickness measurements, and percentage of dead cells at day 11. Results: Of 16 donors who provided corneas, 9 (56%) were male, and the mean (SD) age was 57.9 (12.4) years. Corneas were paired, and baseline parameters were comparable between all groups. At all time points, CEnC loss was lower in the α-MSH groups compared with the control groups. This difference was statistically significant after cytokine-induced stress (20.2% vs 35.2%; sample estimate of median, -14.9; 95% CI, -23.6 to -6.3; P = .008). Compared with the control group, α-MSH treatment resulted in a smaller increase in central corneal thickness (cytokine-induced stress: 89.3 μm vs 169.8 μm; sample estimate of median, -84.9; 95% CI, -131.5 to -41.6; P = .008; oxidative stress: 43.6 μm vs 111.9 μm; sample estimate of median, -68.8; 95% CI, -100.0 to -34.5; P = .008) and a smaller proportion of cell death (cytokine-induced stress: 2.7% vs 10.4%; difference, -7.7; 95% CI, -13.1 to -2.4; P = .01; oxidative stress: 2.9% vs 12.4%; difference, 9.5; 95% CI, 5.1 to 13.9; P = .006). Conclusions and Relevance: In this study, α-MSH treatment attenuated CEnC loss during cold storage after acute oxidative and cytokine-induced stress in human eye bank cold-stored corneas. These data suggest that supplementation of corneal storage solution with α-MSH may positively affect CEnC survival after transplant and protect the endothelium from proinflammatory cytokines and oxidative stress after full-thickness or endothelial keratoplasty, which is particularly valuable in patients at high risk of graft failure.
Papadopoulos Z. Recent Developments in the Treatment of Wet Age-related Macular Degeneration. Curr Med Sci 2020;40(5):851-857.Abstract
Age-related macular degeneration (AMD) is the most common cause of irreversible blindness and visual impairment in individuals over the age of 50 years in western societies. More than 25 million people currently suffer from this illness in the world, with an additional 500 000 every year, approximately. It is a multifactorial ocular disease that affects the maculae due to a late-onset progressive neurodegeneration and dysfunction of photoreceptors and retinal pigment epithelium (RPE). There are many subtypes of AMD but basically two broad forms: the nonneovascular (dry, nonexudative) and neovascular (wet, exudative). Exudative AMD is the less common form (about 15%) but tends to progress more rapidly. At the moment, wet AMD is treated primarily on the basis of anti-vascular endothelial growth factor (VEGF) agents, which have led to massive improvement in the prognosis of the disease since they were first introduced. This article focuses on the latest treatment approaches to neovascular AMD. An extensive literature review was performed in order to illustrate the effectiveness of current and future anti-VEGF agents as well as the landmark clinical studies that have been carried out to establish these drugs as a gold standard in the therapy of wet AMD.
Liu WW, McClurkin M, Tsikata E, Hui P-C, Elze T, Celebi ARC, Khoueir Z, Lee R, Shieh E, Simavli H, Que C, Guo R, de Boer J, Chen TC. Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model. J Glaucoma 2020;29(10):952-963.Abstract
PRECIS: In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. PURPOSE: To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. METHODS: In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. RESULTS: Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P<0.014). Below 31% of global MDB thickness, and 36.8% and 43.6% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates. CONCLUSIONS: When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.
Agranat JS, Douglas VP, Douglas KA, Miller JB. A guarded light pipe for direct visualization during primary scleral buckling on the Ngenuity platform. Int J Retina Vitreous 2020;6:42.Abstract
Background: Visualization during scleral buckling is traditionally achieved via indirect ophthalmoscopy. Recent advances have utilized the surgical microscope and a 25 gauge cannula-based endoillumination system, also known as a Chandelier lighting system. This report details an improved approach using a guarded 25 or 27 gauge light pipe and the Ngenuity digital three dimensional platform. Methods: A standard Alcon light pipe is modified with a silicone guard to expose only 5 mm of the tip of the light pipe. The guard is created from the silicone that is already opened to secure the ends of the encircling band most often employed sleeve (e.g. 70, 270). This guarded light pipe is then inserted into the cannula as an alternative to a Chandelier lighting system. Results: This is a technical report of a surgical visualization technique using a three dimensional digital visualization platform with a modified handheld vitrectomy light pipe. Conclusion: The utilization of a guarded light pipe for visualization during primary scleral buckling is a promising, effective, and efficient technique. The three dimensional digital display allows for better educational impact and surgical communication with trainees and ancillary members of the surgical team.
Dagi LR, Elhusseiny AM. Adjustable graded augmentation of superior rectus transposition for treatment of abducens nerve palsy and Duane syndrome. J AAPOS 2020;Abstract
PURPOSE: To report the results of adjustable graded augmentation of superior rectus transposition, a novel modification of superior rectus transposition (SRT) designed to reduce postoperative vertical or torsional diplopia. METHODS: The medical records of patients who underwent adjustable graded augmentation of SRT with or without adjustable medial rectus recession (MRc) from February 2017 to December 2019 were reviewed retrospectively. A Mendez ring was used to monitor torsional change after transposition of the superior rectus muscle to the lateral rectus muscle and after sequential placement of 2 or 3 augmentation sutures by superior rectus-lateral rectus loop myopexy. If excessive mechanical intorsion was induced, the responsible augmentation suture was severed intraoperatively. If torsional or vertical diplopia was noted after recovery, the distal-most augmentation suture was cut. Exotropia was managed by severing the distal-most augmentation suture or by medial rectus adjustment. RESULTS: A total of 8 patients who underwent adjustable graded augmentation of SRT were included (6 using the 3-suture technique): 3 for esotropic Duane syndrome, 2 for abducens nerve palsy, 1 for Moebius syndrome, and 2 for combined trochlear and abducens nerve palsies. Of the 8 patients, 4 had prior strabismus surgery, and 1 patient had previously undergone treatment with botulinum toxin. Severing one augmentation suture in 3 cases resolved vertical (n = 2) or torsional (n = 1) diplopia and consecutive exotropia (n = 1), resulting in excellent alignment and reduction of torticollis to <4° in 7 cases. The technique proved insufficient in 1 patient, who had undergone 3 prior strabismus procedures. CONCLUSIONS: In this study cohort, adjustable graded augmentation of SRT effectively managed the risk of postoperative vertical or torsional diplopia.
Glassman AR, Wells JA, Josic K, Maguire MG, Antoszyk AN, Baker C, Beaulieu WT, Elman MJ, Jampol LM, Sun JK. Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study). Ophthalmology 2020;127(9):1201-1210.Abstract
PURPOSE: Assess follow-up treatment and clinical outcomes at 5 years in eyes initially treated with anti-VEGF therapy for center-involved diabetic macular edema (CI-DME) in a 2-year randomized clinical trial. DESIGN: Multicenter cohort study. PARTICIPANTS: Participants with diabetic macular edema (DME) and visual acuity (VA) 20/32 to 20/320 enrolled in DRCR.net Protocol T with visits 5 years after randomization (3 years after Protocol T completion). METHODS: Participants were assigned randomly to aflibercept, bevacizumab, or ranibizumab with protocol-defined follow-up and re-treatment for 2 years. Thereafter, participants were managed at clinician discretion and recalled for a 5-year visit. MAIN OUTCOME MEASURES: Anti-vascular endothelial growth factor (VEGF) treatment, VA letter score, and central subfield thickness (CST). RESULTS: Sixty-eight percent (317/463) of eligible participants completed the 5-year visit. Between years 2 and 5, 68% (217/317) of study eyes received at least 1 anti-VEGF treatment (median, 4; interquartile range [IQR], 0-12). At 5 years, mean VA improved from baseline by 7.4 letters (95% confidence interval [CI], 5.9-9.0) but decreased by 4.7 letters (95% CI, 3.3-6.0) between 2 and 5 years. When baseline VA was 20/50 to 20/320, mean 5-year VA was 11.9 letters (95% CI, 9.3-14.5) better than baseline but 4.8 letters (95% CI, 2.5-7.0) worse than 2 years. When baseline VA was 20/32 to 20/40, mean 5-year VA was 3.2 letters (95% CI, 1.4-5.0) better than baseline but 4.6 letters (95% CI, 3.1-6.1) worse than 2 years. Mean CST decreased from baseline to 5 years by 154 μm (95% CI, 142-166) and was stable between 2 and 5 years (-1 μm; 95% CI, -12 to 9). CONCLUSIONS: Among the two-thirds of eligible Protocol T participants who completed a 5-year visit, mean VA improved from baseline to 5 years without protocol-defined treatment after follow-up ended at 2 years. Although mean retinal thickness was similar at 2 and 5 years, mean VA worsened during this period. Additional investigation into strategies to improve long-term outcomes in eyes with DME seems warranted to determine if VA can be better maintained with different management approaches.
Wons J, Kempen J, Garweg JG. HIV-induced Retinitis. Ocul Immunol Inflamm 2020;28(8):1259-1268.Abstract
PURPOSE: To provide an overview of the current knowledge on the Human Immunodeficiency Virus (HIV)-associated retinopathies. METHODS: A PubMed search was performed, using the key terms "HIV Retinopathy OR Retinitis" and "HIV AND Retinitis" to find manuscripts published within the last ten years. RESULTS: If left untreated, HIV infection causes a progressive immunodeficiency caused by depletion of CD4-positive T lymphocytes. Noninfectious HIV retinopathy, clinically manifested by cotton wool spots. Once the CD4 count drops below 200 c/μl, immunodeficiency creates a vulnerability for systemic opportunistic infections. Within the posterior segment of the eye, cytomegalovirus (CMV) retinitis has to be distinguished from infections with other members of the herpes virus family, as well as from toxoplasmosis, tuberculosis, and syphilis. Upon restoration of the immune system, immune recovery uveitis may manifest in one third of CMV affected eyes. CONCLUSION: Targeted antiviral treatment and secondary recurrence prophylaxis prevent vision loss of the retina prior to immune recovery.
Xu L-J, Rong S-S, Xu Y-S, Zheng L-B, Qiu W-Y, Zhang X, Jiang L-J, Duan R-P, Tian T, Yao Y-F. Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva. Exp Eye Res 2020;200:108215.Abstract
This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 μmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 μmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 μmol/L MMC, both 7.5 μmol/L and 15 μmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 μmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 μmol/L prevented postoperative conjunctival fibrosis in an animal model.
Rinaldi L, Ciricugno A, Merabet LB, Vecchi T, Cattaneo Z. The Effect of Blindness on Spatial Asymmetries. Brain Sci 2020;10(10)Abstract
The human cerebral cortex is asymmetrically organized with hemispheric lateralization pervading nearly all neural systems of the brain. Whether the lack of normal visual development affects hemispheric specialization subserving the deployment of visuospatial attention asymmetries is controversial. In principle, indeed, the lack of early visual experience may affect the lateralization of spatial functions, and the blind may rely on a different sensory input compared to the sighted. In this review article, we thus present a current state-of-the-art synthesis of empirical evidence concerning the effects of visual deprivation on the lateralization of various spatial processes (i.e., including line bisection, mirror symmetry, and localization tasks). Overall, the evidence reviewed indicates that spatial processes are supported by a right hemispheric network in the blind, hence, analogously to the sighted. Such a right-hemisphere dominance, however, seems more accentuated in the blind as compared to the sighted as indexed by the greater leftward bias shown in different spatial tasks. This is possibly the result of the more pronounced involvement of the right parietal cortex during spatial tasks in blind individuals compared to the sighted, as well as of the additional recruitment of the right occipital cortex, which would reflect the cross-modal plastic phenomena that largely characterize the blind brain.
Williams PR, Benowitz LI, Goldberg JL, He Z. Axon Regeneration in the Mammalian Optic Nerve. Annu Rev Vis Sci 2020;6:195-213.Abstract
The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.
Rabe BA, Cepko C. SARS-CoV-2 detection using isothermal amplification and a rapid, inexpensive protocol for sample inactivation and purification. Proc Natl Acad Sci U S A 2020;Abstract
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had an enormous impact on society worldwide, threatening the lives and livelihoods of many. The effects will continue to grow and worsen if economies begin to open without the proper precautions, including expanded diagnostic capabilities. To address this need for increased testing, we have developed a sensitive reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay compatible with current reagents, which utilizes a colorimetric readout in as little as 30 min. A rapid inactivation protocol capable of inactivating virions, as well as endogenous nucleases, was optimized to increase sensitivity and sample stability. This protocol, combined with the RT-LAMP assay, has a sensitivity of at least 50 viral RNA copies per microliter in a sample. To further increase the sensitivity, a purification protocol compatible with this inactivation method was developed. The inactivation and purification protocol, combined with the RT-LAMP assay, brings the sensitivity to at least 1 viral RNA copy per microliter in a sample. This simple inactivation and purification pipeline is inexpensive and compatible with other downstream RNA detection platforms and uses readily available reagents. It should increase the availability of SARS-CoV-2 testing as well as expand the settings in which this testing can be performed.
Park EA, Tsikata E, Lee JJ, Shieh E, Braaf B, Vakoc BJ, Bouma BE, de Boer JF, Chen TC. Artifact Rates for 2D Retinal Nerve Fiber Layer Thickness Versus 3D Neuroretinal Rim Thickness Using Spectral-Domain Optical Coherence Tomography. Transl Vis Sci Technol 2020;9(10):10.Abstract
Purpose: To compare the rates of clinically significant artifacts for two-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness versus three-dimensional (3D) neuroretinal rim thickness using spectral-domain optical coherence tomography (SD-OCT). Methods: Only one eye per patient was used for analysis of 120 glaucoma patients and 114 normal patients. For RNFL scans and optic nerve scans, 15 artifact types were calculated per B-scan and per eye. Neuroretinal rim tissue was quantified by the minimum distance band (MDB). Global MDB neuroretinal rim thicknesses were calculated before and after manual deletion of B-scans with artifacts and subsequent automated interpolation. A clinically significant artifact was defined as one requiring manual correction or repeat scanning. Results: Among glaucomatous eyes, artifact rates per B-scan were significantly more common in RNFL scans (61.7%, 74 of 120) compared to B-scans in neuroretinal rim volume scans (20.9%, 1423 of 6820) (95% confidence interval [CI], 31.6-50.0; < 0.0001). For clinically significant artifact rates per eye, optic nerve scans had significantly fewer artifacts (15.8% of glaucomatous eyes, 13.2% of normal eyes) compared to RNFL scans (61.7% of glaucomatous eyes, 25.4% of normal eyes) (glaucoma group: 95% CI, 34.1-57.5, < 0.0001; normal group: 95% CI, 1.3-23.3, = 0.03). Conclusions: Compared to the most commonly used RNFL thickness scans, optic nerve volume scans less frequently require manual correction or repeat scanning to obtain accurate measurements. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

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