September 2018

Wittmann J, Dieckow J, Schröder H, Hampel U, Garreis F, Jacobi C, Milczarek A, Hsieh KL, Pulli B, Chen JW, Hoogeboom S, Bräuer L, Paulsen FP, Schob S, Schicht M. Plasma gelsolin promotes re-epithelialization. Sci Rep 2018;8(1):13140.Abstract
Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.
Shi C, Luo G. A Streaming Motion Magnification Core for Smart Image Sensors. IEEE Trans Circuits Syst II Express Briefs 2018;65(9):1229-1233.Abstract
This paper proposes a modified Eulerian Video Magnification (EVM) algorithm and a hardware implementation of a motion magnification core for smart image sensors. Compared to the original EVM algorithm, we perform the pixel-wise temporal bandpass filtering only once rather than multiple times on all scale layers, to reduce the memory and multiplier requirement for hardware implementation. A pixel stream processing architecture with pipelined blocks is proposed for the magnification core, enabling it to readily fit common image sensing components with streaming pixel output, while achieving higher performance with lower system cost. We implemented an FPGA-based prototype that is able to process up to 90M pixels per second and magnify subtle motion. The motion magnification results are comparable to the original algorithm running on PC.
Sharma M, MacKinnon S, Zurakowski D, Dagi LR. Consecutive superior oblique palsy after adjustable suture spacer surgery for Brown syndrome: incidence and predicting risk. J AAPOS 2018;Abstract
PURPOSE: To determine the incidence of and to identify characteristics predicting significant superior oblique palsy (SOP) after adjustable superior oblique suture spacer surgery for treatment of Brown syndrome. METHODS: The medical records of patients treated for unilateral Brown syndrome with adjustable suture spacers (2005-2016) were reviewed to identify possible association of age at surgery, spacer length, surgeon performing procedure, severity of Brown syndrome, preoperative hypotropia in primary position and affected side gaze, and reduction in Brown restriction on postoperative superior oblique function. "Good" postoperative superior oblique function was defined as absence of hypertropia and diplopia in primary position and no more than intermittent diplopia in downgaze comfortably fused with ≤4Δ base-down or head tilt of <10°. Presence of postoperative hypertropia in primary position with increase in downgaze met criteria for significant SOP. Postoperative Brown restriction of ≤ -2 indicated resolution of Brown syndrome. RESULTS: Median age at surgery was 59 months, interquartile range (IQR) was 32-82 months, and median spacer length was 6 mm (range, 2-7 mm) for 19 included patients. Preoperative median hypotropia was 9Δ (IQR, 0Δ-12Δ) in primary position and 18Δ (IQR, 5Δ-22Δ) in affected side gaze. Of 19 patients, 16 (84%) achieved sufficient resolution of Brown syndrome, but 6 (32%) developed significant SOP. Modest preoperative hypotropia in affected side gaze was the only predictor of significant SOP (likelihood ratio test = 7.11; P = 0.008). Logistic regression modeling enabled estimation of risk of significant SOP based on preoperative side gaze hypotropia. CONCLUSIONS: Suture spacer surgery can result in significant SOP. Risk may be predicted by magnitude of preoperative side gaze hypotropia.
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.
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.
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.
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.
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.
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.
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.
Hudry E, Andres-Mateos E, Lerner EP, Volak A, Cohen O, Hyman BT, Maguire CA, Vandenberghe LH. Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65. Mol Ther Methods Clin Dev 2018;10:197-209.Abstract
Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65's diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.
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.
Satitpitakul V, Sun Z, Suri K, Amouzegar A, Katikireddy KR, Jurkunas UV, Kheirkhah A, Dana R. Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival. Am J Pathol 2018;188(9):2016-2024.Abstract
Corneal transplantation is the most prevalent form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain graft transparency. CEnC density decreases significantly after corneal transplantation even in the absence of graft rejection. To date, different strategies have been used to enhance CEnC survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC integrity during donor cornea tissue storage and protects CEnCs against oxidative stress-induced apoptosis. However, little is known about the effect of exogenous administration of VIP on corneal transplant outcomes. We found that VIP significantly accelerates endothelial wound closure and suppresses interferon-γ- and tumor necrosis factor-α-induced CEnC apoptosis in vitro in a dose-dependent manner. In addition, we found that intracameral administration of VIP to mice undergoing syngeneic corneal transplantation with endothelial injury increases CEnC density and decreases graft opacity scores. Finally, using a mouse model of allogeneic corneal transplantation, we found for the first time that treatment with VIP significantly suppresses posttransplantation CEnC loss and improves corneal allograft survival.

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