Arboleda-Velasquez J. Safe and Effective Disease-Modifying Therapies for Small Blood Vessel Disease in the Brain. Am J Pathol. 2021;191(11):1852–1855.
Publications
2021
Maidana D, Gonzalez-Buendia L, Miller J, Vavvas D. Local photoreceptor cell death differences in the murine model of retinal detachment. Sci Rep. 2021;11(1):18798.
To investigate local cell death differences in the attached and detached retina at different regions in a murine experimental retinal detachment model. Subretinal injection of sodium hyaluronate was performed in eight-week-old C57BL/6J mice. Retinal regions of interest were defined in relation to their distance from the peak of the retinal detachment, as follows: (1) attached central; (2) attached paracentral; (3) detached apex; and (4) detached base. At day 0, the outer nuclear layer cell count for the attached central, attached paracentral, detached apex, and detached base was 1247.60 ± 64.62, 1157.80 ± 163.33, 1264.00 ± 150.7, and 1013.80 ± 67.16 cells, respectively. There were significant differences between the detached base vs. attached central, and between detached base vs. detached apex at day 0. The detached apex region displayed a significant and progressive cell count reduction from day 0 to 14. In contrast, the detached base region did not show progressive retinal degeneration in this model. Moreover, only the detached apex region had a significant and progressive cell death rate compared to baseline. Immediate confounding changes with dramatic differences in cell death rates are present across regions of the detached retina. We speculate that mechanical and regional differences in the bullous detached retina can modify the rate of cell death in this model.
Neitzel A, Wolf B, Guo X, Shakarchi A, Madden N, Repka M, Friedman D, Collins M. Effect of a Randomized Interventional School-Based Vision Program on Academic Performance of Students in Grades 3 to 7: A Cluster Randomized Clinical Trial. JAMA Ophthalmol. 2021;139(10):1104–1114.
Importance: Uncorrected refractive error in school-aged children may affect learning. Objective: To assess the effect of a school-based vision program on academic achievement among students in grades 3 to 7. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Baltimore City Public Schools during school years from 2016 to 2019 among 2304 students in grades 3 to 7 who received eye examinations and eyeglasses. Intervention: Participating schools were randomized 1:1:1 to receive eye examinations and eyeglasses during 1 of 3 school years (2016-2017, 2017-2018, and 2018-2019). Main Outcomes and Measures: The primary outcome was 1-year intervention impact, measured by effect size (ES), defined as the difference in score on an academic test (i-Ready or Partnership for Assessment of Readiness for College and Careers tests on reading and mathematics) between intervention and control groups measured in SD units, comparing cohort 1 (intervention) with cohorts 2 and 3 (control) at the end of program year 1 and comparing cohort 2 (intervention) with cohort 3 (control) at the end of program year 2. The secondary outcome was 2-year intervention impact, comparing ES in cohort 1 (intervention) with cohort 3 (control) at the end of program year 2. Hierarchical linear modeling was used to assess the impact of the intervention. Analysis was performed on an intention-to-treat basis. Results: Among the 2304 students included in the study, 1260 (54.7%) were girls, with a mean (SD) age of 9.4 (1.4) years. The analysis included 964 students (41 schools) in cohort 1, 775 students (41 schools) in cohort 2, and 565 students (38 schools) in cohort 3. There were 1789 Black students (77.6%), 388 Latinx students (16.8%), and 406 students in special education (17.6%). There was an overall 1-year positive impact (ES, 0.09; P = .02) as assessed by the i-Ready reading test during school year 2016-2017. Positive impact was also observed among female students (ES, 0.15; P < .001), those in special education (ES, 0.25; P < .001), and students who performed in the lowest quartile at baseline (ES, 0.28; P < .001) on i-Ready reading and among students in elementary grades on i-Ready mathematics (ES, 0.03; P < .001) during school year 2016-2017. The intervention did not show a sustained impact at 2 years or on Partnership for Assessment of Readiness for College and Careers testing. Conclusions and Relevance: Students in grades 3 to 7 who received eyeglasses through a school-based vision program achieved better reading scores. Students had improved academic achievement over 1 year; however, a sustained impact was not observed after 2 years. Trial Registration: The Registry of Efficacy and Effectiveness Studies Identifier: 1573.1v1.
Wishart T, Flokis M, Shu D, Das S, Lovicu F. Hallmarks of lens aging and cataractogenesis. Exp Eye Res. 2021;210:108709.
Lens homeostasis and transparency are dependent on the function and intercellular communication of its epithelia. While the lens epithelium is uniquely equipped with functional repair systems to withstand reactive oxygen species (ROS)-mediated oxidative insult, ROS are not necessarily detrimental to lens cells. Lens aging, and the onset of pathogenesis leading to cataract share an underlying theme; a progressive breakdown of oxidative stress repair systems driving a pro-oxidant shift in the intracellular environment, with cumulative ROS-induced damage to lens cell biomolecules leading to cellular dysfunction and pathology. Here we provide an overview of our current understanding of the sources and essential functions of lens ROS, antioxidative defenses, and changes in the major regulatory systems that serve to maintain the finely tuned balance of oxidative signaling vs. oxidative stress in lens cells. Age-related breakdown of these redox homeostasis systems in the lens leads to the onset of cataractogenesis. We propose eight candidate hallmarks that represent common denominators of aging and cataractogenesis in the mammalian lens: oxidative stress, altered cell signaling, loss of proteostasis, mitochondrial dysfunction, dysregulated ion homeostasis, cell senescence, genomic instability and intrinsic apoptotic cell death.
Cui Y, Zhu Y, Lu E, Le R, Laíns I, Katz R, Wang J, Garg I, Lu Y, Zeng R, Eliott D, Vavvas D, Husain D, Miller J, Kim L, Wu D, Miller J. Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study. Ophthalmology. 2021;128(9):1312–1324.
PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.
Dana R, Farid M, Gupta P, Hamrah P, Karpecki P, McCabe C, Nijm L, Pepose J, Pflugfelder S, Rapuano C, Saini A, Gibbs S, Broder M. Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy. BMC Ophthalmol. 2021;21(1):327.
BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.
Muralidharan S, Ichhpujani P, Bhartiya S, Singh RB. Eye-tunes: role of music in ophthalmology and vision sciences. Ther Adv Ophthalmol. 2021;13:25158414211040890.
Although the healing effect of music has been recognized since time immemorial, there has been a renewed interest in its use in modern medicine. This can be attributed to the increasing focus on holistic healing and on the subjective and objective aspects of well-being. In ophthalmology, this has ranged from using music for patients undergoing diagnostic procedures and surgery, as well as for doctors and the operation theatre staff during surgical procedures. Music has proven to be a potent nonpharmacological sedative and anxiolytic, allaying both the pain and stress of surgery. This review aims to explore the available evidence about the role of music as an adjunct for diagnostic and surgical procedures in current ophthalmic practices.
Pamir Z, Bauer C, Bennett C, Kran B, Merabet L. Visual perception supported by verbal mediation in an individual with cerebral visual impairment (CVI). Neuropsychologia. 2021;160:107982.
Cerebral visual impairment (CVI) often presents with deficits associated with higher order visual processing. We report a case of an individual with CVI who uses a verbal mediation strategy to perceive and interact with his visual surroundings. Visual perceptual performance was assessed using a virtual reality based visual search task combined with eye tracking. Functional magnetic resonance imaging (fMRI) was employed to identify the neural correlates associated with this strategy. We found that when using verbal mediation, the individual could readily detect and track the target within the visual scene which was associated with robust activation within a network of occipito-parieto-temporal visual cortical areas. In contrast, when not using verbal mediation, the individual was completely unable to perform the task, and this was associated with dramatically reduced visual cortical activation. This unique compensatory strategy may be related to the individual's use of verbal working memory for the purposes of understanding complex visual information.
Jowett N, Pineda R. Corneal and Facial Sensory Neurotization in Trigeminal Anesthesia. Facial Plast Surg Clin North Am. 2021;29(3):459–470.
Trigeminal anesthesia may yield blindness and facial disfigurement, secondary to neurotrophic keratopathy and trigeminal trophic syndrome. This article summarizes contemporary medical and emerging surgical approaches for the therapeutic management of this rare and devastating disease state.
Jowett N, Pineda R. Seeing through the evidence for corneal neurotization. Curr Opin Otolaryngol Head Neck Surg. 2021;29(4):252–258.
PURPOSE OF REVIEW: Trigeminal anesthesia causes neurotrophic keratopathy, which may yield facial disfigurement and corneal blindness. RECENT FINDINGS: We summarize approaches and evidence for corneal neurotization. SUMMARY: Regional sensory nerve transfer appears safe and effective for therapeutic management of neurotrophic keratopathy. Prospective randomized clinical trials are necessary to confirm the utility of corneal neurotization.
