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Palmer EM, Van Wert MJ, Horowitz TS, Wolfe JM. Measuring the time course of selection during visual search. Atten Percept Psychophys 2018;Abstract
In visual search tasks, observers can guide their attention towards items in the visual field that share features with the target item. In this series of studies, we examined the time course of guidance toward a subset of items that have the same color as the target item. Landolt Cs were placed on 16 colored disks. Fifteen distractor Cs had gaps facing up or down while one target C had a gap facing left or right. Observers searched for the target C and reported which side contained the gap as quickly as possible. In the absence of other information, observers must search at random through the Cs. However, during the trial, the disks changed colors. Twelve disks were now of one color and four disks were of another color. Observers knew that the target C would always be in the smaller color set. The experimental question was how quickly observers could guide their attention to the smaller color set. Results indicate that observers could not make instantaneous use of color information to guide the search, even when they knew which two colors would be appearing on every trial. In each study, it took participants 200-300 ms to fully utilize the color information once presented. Control studies replicated the finding with more saturated colors and with colored C stimuli (rather than Cs on colored disks). We conclude that segregation of a display by color for the purposes of guidance takes 200-300 ms to fully develop.
Singh RB, Batta P. Herpes simplex virus keratitis mimicking Acanthamoeba keratitis: a clinicopathological correlation. BMJ Case Rep 2018;2018Abstract
A 36-year-old male, soft contact lens wearer was referred by his primary ophthalmologist for corneal ulcer of the right eye (OD), which was persistent despite topical fluoroquinolone therapy for 1 month. A ring-shaped infiltrate typically seen in Acanthamoeba infection was noted, and topical therapy with chlorhexidine and polyhexamethylene biguanide was initiated. However, the patient's condition deteriorated over the next several weeks; thus, diagnostic and therapeutic penetrating keratoplasty was performed. The postoperative immunohistochemical analysis suggested a diagnosis of herpes simplex virus (HSV) keratitis. The patient ultimately improved after initiation of oral valacyclovir following penetrating keratoplasty. We report a case of a commonly encountered clinical entity, HSV keratitis, with an atypical clinical presentation, masquerading as Acanthamoeba keratitis.
Qiu C, Jung J-H, Tuccar-Burak M, Spano L, Goldstein R, Peli E. Measuring Pedestrian Collision Detection With Peripheral Field Loss and the Impact of Peripheral Prisms. Transl Vis Sci Technol 2018;7(5):1.Abstract
Purpose: Peripheral field loss (PFL) due to retinitis pigmentosa, choroideremia, or glaucoma often results in a highly constricted residual central field, which makes it difficult for patients to avoid collision with approaching pedestrians. We developed a virtual environment to evaluate the ability of patients to detect pedestrians and judge potential collisions. We validated the system with both PFL patients and normally sighted subjects with simulated PFL. We also tested whether properly placed high-power prisms may improve pedestrian detection. Methods: A virtual park-like open space was rendered using a driving simulator (configured for walking speeds), and pedestrians in testing scenarios appeared within and outside the residual central field. Nine normally sighted subjects and eight PFL patients performed the pedestrian detection and collision judgment tasks. The performance of the subjects with simulated PFL was further evaluated with field of view expanding prisms. Results: The virtual system for testing pedestrian detection and collision judgment was validated. The performance of PFL patients and normally sighted subjects with simulated PFL were similar. The prisms for simulated PFL improved detection rates, reduced detection response times, and supported reasonable collision judgments in the prism-expanded field; detections and collision judgments in the residual central field were not influenced negatively by the prisms. Conclusions: The scenarios in a virtual environment are suitable for evaluating PFL and the impact of field of view expanding devices. Translational Relevance: This study validated an objective means to evaluate field expansion devices in reproducible near-real-life settings.
Sun Y, Smith LEH. Retinal Vasculature in Development and Diseases. Annu Rev Vis Sci 2018;4:101-122.Abstract
The retina is one of the most metabolically active tissues in the body, consuming high levels of oxygen and nutrients. A well-organized ocular vascular system adapts to meet the metabolic requirements of the retina to ensure visual function. Pathological conditions affect growth of the blood vessels in the eye. Understanding the neuronal biological processes that govern retinal vascular development is of interest for translational researchers and clinicians to develop preventive and interventional therapeutics for vascular eye diseases that address early drivers of abnormal vascular growth. This review summarizes the current knowledge of the cellular and molecular processes governing both physiological and pathological retinal vascular development, which is dependent on the interaction among retinal cell populations, including neurons, glia, immune cells, and vascular endothelial cells. We also review animal models currently used for studying retinal vascular development.
Yazdani M, Chen X, Tashbayev B, Utheim ØA, Ræder S, Lagli N, Stojanovic A, Dartt DA, Utheim TP. Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort. Curr Eye Res 2018;43(12):1465-1470.Abstract
PURPOSE: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. METHODS: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p ≤ 0.05). RESULTS: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). CONCLUSIONS: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.
Bernabeu MO, Lu Y, Abu-Qamar O, Aiello LP, Sun JK. Estimation of Diabetic Retinal Microaneurysm Perfusion Parameters Based on Computational Fluid Dynamics Modeling of Adaptive Optics Scanning Laser Ophthalmoscopy. Front Physiol 2018;9:989.Abstract
Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microaneurysms (MAs), which are abnormal outpouchings of the retinal vessels, are early and hallmark lesions of DR. The presence and severity of MAs are utilized to determine overall DR severity. In addition, MAs can directly contribute to retinal neural pathology by leaking fluid into the surrounding retina, causing abnormal central retinal thickening and thereby frequently leading to vision loss. Vascular perfusion parameters such as shear rate (SR) or wall shear stress (WSS) have been linked to blood clotting and endothelial cell dysfunction, respectively in non-retinal vasculature. However, despite the importance of MAs as a key aspect of diabetic retinal pathology, much remains unknown as to how structural characteristics of individual MAs are associated with these perfusion attributes. MA structural information obtained on high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) was utilized to estimate perfusion parameters through Computational Fluid Dynamics (CFD) analysis of the AOSLO images. The HemeLB flow solver was used to simulate steady-state and time-dependent fluid flow using both commodity hospital-based and high performance computing resources, depending on the degree of detail required in the simulations. Our results indicate that WSS is lowest in MA regions furthest away from the feeding vessels. Furthermore, areas of low SR are associated with clot location in saccular MAs. These findings suggest that morphology and CFD estimation of perfusion parameters may be useful tools for determining the likelihood of clot presence in individual diabetic MAs.
Ebrahimiadib N, Ma L, Modjtahedi BS, Davoudi S, Rahmani S, Syeda S, Stephenson A, Foster CS. Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases. Ocul Immunol Inflamm 2018;:1-5.Abstract
PURPOSE: To characterize the clinical features of patients with ocular inflammatory diseases (OID) who tested positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). METHODS: Retrospective case series of patients with OID seen at the Massachusetts Eye Research and Surgery Institute (MERSI) from April 2014 to April 2016. RESULTS: 813 patients were tested for ANCA with 34 patients (4%) being positive for atypical P-ANCA. Among those with positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in 62% (n = 21) followed by scleritis in 20% (n = 7). Only one patient had an episode of recurrent disease flare-up. All but one patient, who had concomitant C-ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease course with controlled inflammation using topical and/or systemic immunomodulatory therapy. CONCLUSION: In contrast to typical C-ANCA and P-ANCA, atypical P-ANCA seropositivity was not associated with severe vasculitis or poor prognosis in patients with the OID.
Aggarwal S, Cavalcanti BM, Regali L, Cruzat A, Trinidad M, Williams C, Jurkunas UV, Hamrah P. In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy. Am J Ophthalmol 2018;196:136-144.Abstract
PURPOSE: To evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss. DESIGN: Prospective, cross-sectional, controlled study. METHODS: Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters. RESULTS: FECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm, respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm; P = .01), but not in PBK (47.7 ± 11.6 cells/mm; P = .60) compared to controls (22.5 ± 4.5 cells/mm). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm). CONCLUSION: IVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.
Kobashi H, Ciolino JB. Innovative Development of Contact Lenses. Cornea 2018;37 Suppl 1:S94-S98.Abstract
Contact lenses have been a common means of vision correction for more than half a century. Recent developments have raised the possibility that the next few decades will see a considerable broadening of the range of applications for contact lenses, with associated expansions in the number and type of individuals who consider them a valuable option. The novel applications of contact lenses include treatment platforms for myopic progression, biosensors, and ocular drug delivery. Orthokeratology has shown the most consistent treatment for myopia control with the least side effects. Recent work has resulted in commercialization of a device to monitor intraocular pressure for up to 24 hours, and extensive efforts are underway to develop a contact lens sensor capable of continuous glucose tear film monitoring for the management of diabetes. Other studies on drug-eluting contact lenses have focused on increasing the release duration through molecular imprinting, use of vitamin E, and increased drug binding to polymers by sandwiching a poly (lactic-co-glycolic acid) layer in the lens. This review demonstrates the potential for contact lenses to provide novel opportunities for refractive management, diagnosis, and management of diseases.
Chen H, Cho K-S, Vu KTH, Shen C-H, Kaur M, Chen G, Mathew R, McHam LM, Fazelat A, Lashkari K, Au NPB, Tse JKY, Li Y, Yu H, Yang L, Stein-Streilein J, Ma CHE, Woolf CJ, Whary MT, Jager MJ, Fox JG, Chen J, Chen DF. Author Correction: Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun 2018;9(1):3914.Abstract
The originally published version of this Article contained an error in Figure 4. The bar chart in panel f was inadvertently replaced with a duplicate of the bar chart in panel e. This error has now corrected in both the PDF and HTML versions of the Article.
Agarwal A, Invernizzi A, Singh RB, Foulsham W, Aggarwal K, Handa S, Agrawal R, Pavesio C, Gupta V. An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management. J Ophthalmic Inflamm Infect 2018;8(1):13.Abstract
Inflammatory choroidal neovascular membranes are challenging to diagnose and manage. A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity. In conditions such as punctate inner choroidopathy, development of choroidal neovascularization is extremely common and must be suspected in all cases. On the other hand, in patients with conditions such as serpiginous choroiditis, and multifocal choroiditis, it may be difficult to differentiate between inflammatory choroiditis lesions and choroidal neovascularization. Multimodal imaging analysis, including the recently introduced technology of optical coherence tomography angiography, greatly aid in the diagnosis and management of inflammatory choroidal neovascularization. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy.
Margeta MA, Lad EM, Proia AD. CD163+ macrophages infiltrate axon bundles of postmortem optic nerves with glaucoma. Graefes Arch Clin Exp Ophthalmol 2018;256(12):2449-2456.Abstract
PURPOSE: Prior research in animal models has shown that macrophages and microglia play an important role in pathogenesis of glaucoma, but the phenotype and distribution of macrophages in human glaucomatous tissue have not been sufficiently characterized. METHODS: We analyzed H&E, CD68-, and CD163-immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. The diagnosis of glaucoma was made based on a history of glaucoma as reported in the medical record and histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race. RESULTS: Qualitative analysis of the conventional outflow pathway and the optic nerve revealed that all eyes contained CD163+ cells but a negligible number of CD68+ cells. CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm's canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In optic nerves of control eyes, CD163+ macrophages were present at low levels and restricted to septa between axon bundles. In glaucomatous optic nerves, the number of CD163+ cells was increased both qualitatively and quantitatively (glaucoma 5.1 ± 0.6 CD163+ cells/mm, control 2.5 ± 0.3 CD163+ cells/mm, p < 0.001), with CD163+ cells infiltrating axon bundles in cases of both mild and severe diseases. CONCLUSIONS: The increase in CD163+ cell number in eyes with mild and severe glaucoma is the first demonstration of macrophage infiltration in glaucomatous human optic nerves. This finding supports a role for macrophages in glaucoma pathogenesis and progression.
Jung J-H, Peli E. No Useful Field Expansion with Full-field Prisms. Optom Vis Sci 2018;95(9):805-813.Abstract
SIGNIFICANCE: Full-field prisms that fill the entire spectacle eye wire have been considered as field expansion devices for homonymous hemianopia (HH) and acquired monocular vision (AMV). Although the full-field prism is used for addressing binocular dysfunction and for prism adaptation training after brain injury as treatment for spatial hemineglect, we show that the full-field prism for field expansion does not effectively expand the visual field in either HH or AMV. PURPOSE: Full-field prisms may shift a portion of the blind side to the residual seeing side. However, foveal fixation on an object of interest through a full-field prism requires head and/or eye rotation away from the blind side, thus negating the shift of the field toward the blind side. METHODS: We fit meniscus and flat full-field 7Δ and 12Δ yoked prisms and conducted Goldmann perimetry in HH and AMV. We compared the perimetry results with ray tracing calculations. RESULTS: The rated prism power was in effect at the primary position of gaze for all prisms, and the meniscus prisms maintained almost constant power at all eccentricities. To fixate on the perimetry target, the subjects needed to turn their head and/or eyes away from the blind side, which negated the field shift into the blind side. In HH, there was no difference in the perimetry results on the blind side with any of the prisms. In AMV, the lower nasal field of view was slightly shifted into the blind side with the flat prisms, but not with the meniscus prisms. CONCLUSIONS: Full-field prisms are not an effective field expansion device owing to the inevitable fixation shift. There is potential for a small field shift with the flat full-field prism in AMV, but such lenses cannot incorporate refractive correction. Furthermore, in considering the apical scotoma, the shift provides a mere field substitution at best.
Hoshi S, Okamoto F, Arai M, Hirose T, Sugiura Y, Murakami T, Oshika T. Patching retinal breaks with polyethylene glycol-based synthetic hydrogel sealant for retinal detachment in rabbits. Exp Eye Res 2018;177:117-121.Abstract
The purpose of this study was to evaluate absorbable polyethylene glycol (PEG)-based synthetic hydrogel as a sealant for retinal breaks in rhegmatogenous retinal detachment (RD). A three-port, 25-gauge vitrectomy was performed on nine Dutch pigmented rabbit eyes. Subsequently, RD was induced by creating a retinal break. The retina was then reattached by fluid-air exchange. In six of nine eyes (RD-PEG group), PEG sealant was applied to completely cover the retinal breaks, and then photopolymerized with light; thereafter, intravitreous air was replaced with balanced salt solution (BSS). In the remaining three eyes (RD group), PEG sealant was not applied, but the intravitreous air was replaced with BSS. Ophthalmological examinations and intraocular pressure measurements were conducted preoperatively, and at 1 and 7 days, and 1, 3, and 6 months postoperatively. Histological examinations of the eyes were performed after 6 postoperative months. At surgery, retinal reattachment with PEG sealant was achieved in all eyes in the RD-PEG group. Fundoscopic and optical coherence tomographic examinations revealed that the retina remained attached in all the eyes of the RD-PEG group throughout the 6-month observation period. Histological examination revealed no signs of damage in the retinal layers at the edges of the retinal breaks that were in contact with the sealant. In the RD group, the retinas detached in all eyes within 7 days postoperatively. The PEG sealant closed the retinal breaks and maintained retinal reattachment. Intraocular tamponade was not necessary.

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