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Bansal AK, Singer JM, Anderson WS, Golby A, Madsen JR, Kreiman G. Temporal stability of visually selective responses in intracranial field potentials recorded from human occipital and temporal lobes. J Neurophysiol 2012;108(11):3073-86.Abstract
The cerebral cortex needs to maintain information for long time periods while at the same time being capable of learning and adapting to changes. The degree of stability of physiological signals in the human brain in response to external stimuli over temporal scales spanning hours to days remains unclear. Here, we quantitatively assessed the stability across sessions of visually selective intracranial field potentials (IFPs) elicited by brief flashes of visual stimuli presented to 27 subjects. The interval between sessions ranged from hours to multiple days. We considered electrodes that showed robust visual selectivity to different shapes; these electrodes were typically located in the inferior occipital gyrus, the inferior temporal cortex, and the fusiform gyrus. We found that IFP responses showed a strong degree of stability across sessions. This stability was evident in averaged responses as well as single-trial decoding analyses, at the image exemplar level as well as at the category level, across different parts of visual cortex, and for three different visual recognition tasks. These results establish a quantitative evaluation of the degree of stationarity of visually selective IFP responses within and across sessions and provide a baseline for studies of cortical plasticity and for the development of brain-machine interfaces.
Durrani K, Foster SC. Fundus autofluorescence imaging in posterior uveitis. Semin Ophthalmol 2012;27(5-6):228-35.Abstract
Although the phenomenon of fundus autofluorescence has been known for decades, it has only recently been recognized as a measure of retinal pigment epithelial function and health. Characteristic fundus autofluorescence patterns have been described in eyes affected by inflammation of the posterior segment, and these patterns have provided insights into the pathogenesis of posterior uveitis entities. In addition, preliminary data indicate that fundus autofluorescence characteristics may serve as markers of disease activity, allow prediction of visual prognosis, and may help determine the adequacy of therapy. We provide an overview of the current state of fundus autofluorescence imaging technology and review our current knowledge of fundus autoflourescence findings and their clinical use in the posterior uveitis entities.
Daniels AB, Sandberg MA, Chen J, Weigel-DiFranco C, Fielding Hejtmancic J, Berson EL. Genotype-phenotype correlations in Bardet-Biedl syndrome. Arch Ophthalmol 2012;130(7):901-7.Abstract
OBJECTIVE: To determine whether mutations in different Bardet-Biedl syndrome (BBS) genes result in different ocular phenotypes. METHODS: Thirty-seven patients from 31 families were enrolled who met the clinical criteria for BBS and for whom a BBS mutation had been identified. Seventeen patients harbored mutations in BBS1, 10 in BBS10, and 10 in other genes (BBS2, BBS3, BBS5, BBS7, and BBS12). All the patients underwent ocular examination; 36 patients had computerized full-field electroretinograms (ERGs). RESULTS: Visual acuity was significantly better in BBS1 patients than in patients with other BBS mutations (P=.01), and a larger proportion of BBS1 patients had good (≥20/50) visual acuity (P=.01). The ERG amplitudes were significantly higher in BBS1 patients than in patients with other BBS mutations in response to 0.5-Hz and 30-Hz flashes (P<.001 for both). All the BBS1 patients harbored at least 1 missense mutation compared with only 45% of patients with mutations in other BBS genes (P<.001); the rest harbored only null alleles. However, multivariate analysis demonstrated that visual acuity or ERG amplitude did not depend on the type of mutation present (missense or null) when controlling for BBS gene. Prevalences of bone spicule pigmentation and cataract were comparable in BBS subtypes. CONCLUSIONS: Patients with BBS1 mutations had a milder phenotype than did patients with mutations in other BBS genes. Clinically, this manifested as significantly better visual acuity and larger ERG amplitudes. CLINICAL RELEVANCE: These phenotypic differences can help guide genetic testing and genetic counseling for patients with this syndrome.
Chen J, Stahl A, Krah NM, Seaward MR, Joyal J-S, Juan AM, Hatton CJ, Aderman CM, Dennison RJ, Willett KL, Sapieha P, Smith LEH. Retinal expression of Wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice. PLoS One 2012;7(1):e30203.Abstract
Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout (Lrp5(-/-)) mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing Lrp5(-/-) mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from Lrp5(-/-) and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in Lrp5(-/-) retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in Lrp5(-/-) retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in Lrp5(-/-) retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR.
Joyce NC. Proliferative capacity of corneal endothelial cells. Exp Eye Res 2012;95(1):16-23.Abstract
The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic "pump" functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the in vivo induction of transient corneal endothelial cell division or the in vitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new treatments to restore corneal clarity.
Hunter RS, Skondra D, Papaliodis G, Sobrin L. Role of OCT in the diagnosis and management of macular edema from uveitis. Semin Ophthalmol 2012;27(5-6):236-41.Abstract
Uveitis is a potentially visually threatening disease accounting for 10% of vision loss in the developed world. The most common cause of vision loss in patients with uveitis has been shown to be macular edema (ME). The early detection and management of ME is critical to preserve vision in these patients. Optical coherence tomography (OCT) is a valuable tool in the management of many ocular diseases. The use of OCT has revolutionized the diagnosis and management of macular edema from a wide variety of ophthalmological diseases, including uveitis. In this review, we evaluate the role of OCT in the diagnosis and management of uveitic macular edema.
Hamrah P, Sahin A, Dastjerdi MH, Shahatit BM, Bayhan HA, Dana R, Pavan-Langston D. Cellular changes of the corneal epithelium and stroma in herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology 2012;119(9):1791-7.Abstract
PURPOSE: To analyze the morphologic features of corneal epithelial cells and keratocytes by in vivo confocal microscopy in patients with herpes simplex keratitis (HSK) as associated with corneal innervation. DESIGN: Prospective, cross-sectional, controlled, single-center study. PARTICIPANTS: Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). METHODS: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<2.5 cm) loss of sensation. MAIN OUTCOME MEASURES: Changes in morphologic features and density of the superficial and basal epithelial cells, as well as stromal keratocytes, were assessed by 2 masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves. RESULTS: There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50 ± 24.4 cells/mm(2) in eyes with severe sensation loss and 2435.23 ± 224.3 cells/mm(2) in control eyes (P = 0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 μm(2)) compared with contralateral or normal eyes (407.4 μm(2); P = 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4%), mild (29.1%), and severe (52.2%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphologic features correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes compared with controls. CONCLUSIONS: In vivo confocal microscopy reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. This study demonstrated that these changes correlate strongly with changes in corneal innervation.
Bowers AR, Tant M, Peli E. A pilot evaluation of on-road detection performance by drivers with hemianopia using oblique peripheral prisms. Stroke Res Treat 2012;2012:176806.Abstract
Aims. Homonymous hemianopia (HH), a severe visual consequence of stroke, causes difficulties in detecting obstacles on the nonseeing (blind) side. We conducted a pilot study to evaluate the effects of oblique peripheral prisms, a novel development in optical treatments for HH, on detection of unexpected hazards when driving. Methods. Twelve people with complete HH (median 49 years, range 29-68) completed road tests with sham oblique prism glasses (SP) and real oblique prism glasses (RP). A masked evaluator rated driving performance along the 25 km routes on busy streets in Ghent, Belgium. Results. The proportion of satisfactory responses to unexpected hazards on the blind side was higher in the RP than the SP drive (80% versus 30%; P = 0.001), but similar for unexpected hazards on the seeing side. Conclusions. These pilot data suggest that oblique peripheral prisms may improve responses of people with HH to blindside hazards when driving and provide the basis for a future, larger-sample clinical trial. Testing responses to unexpected hazards in areas of heavy vehicle and pedestrian traffic appears promising as a real-world outcome measure for future evaluations of HH rehabilitation interventions aimed at improving detection when driving.
Fay A, Santiago YMB. A modified levine palpebral spring for the treatment of myogenic ptosis. Ophthalmic Plast Reconstr Surg 2012;28(5):372-5.Abstract
PURPOSE: Surgical treatment of myogenic ptosis usually requires a form of frontalis suspension. Complications can include entropion, headache, contour abnormalities, and poor eyelid excursion. The Levine palpebral spring has been used successfully to augment eyelid closure in more than 2,000 patients. The authors present a modified Levine spring to correct ptosis in a patient with poor levator function. METHODS: Interventional case report. A 55-year-old man with profound myogenic ptosis was treated with bilateral modified Levine palpebral springs. Eyelid position, contour and excursion, blink reflex, lagophthalmos, and ocular surface were evaluated. RESULTS: The Levine palpebral spring functioned well to open both eyelids. Margin reflex distance improved from -3 mm to 3 m postoperatively. Excellent contour and excursion were observed. Orbicularis action, including blink reflex, was preserved, and ocular surface was not compromised. CONCLUSION: The modified Levine palpebral spring is an alternative to frontalis suspension in treating select patients with eyelid ptosis with poor levator function.
Al-Latayfeh M, Silva PS, Sun JK, Aiello LP. Antiangiogenic therapy for ischemic retinopathies. Cold Spring Harb Perspect Med 2012;2(6):a006411.Abstract
Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases.
Dela Paz NG, Walshe TE, Leach LL, Saint-Geniez M, D'Amore PA. Role of shear-stress-induced VEGF expression in endothelial cell survival. J Cell Sci 2012;125(Pt 4):831-43.Abstract
Vascular endothelial growth factor (VEGF) plays a crucial role in developmental and pathological angiogenesis. Expression of VEGF in quiescent adult tissue suggests a potential role in the maintenance of mature blood vessels. We demonstrate, using a Vegf-lacZ reporter mouse model, that VEGF is expressed by arterial but not by venous or capillary endothelial cells (ECs) in vivo. Using an in vitro model, we show that arterial shear stress of human umbilical vein ECs (HUVECs) decreases apoptosis and increases VEGF expression, which is mediated by the induction of Krüppel-like factor 2 (KLF2). Additionally, shear stress stimulates the expression of VEGF receptor 2 (VEGFR2) and is associated with its activation. Knockdown of VEGF in shear stressed HUVECs blocks the protective effect of shear stress, resulting in EC apoptosis equivalent to that in control ECs cultured under static conditions. Similarly, treatment of ECs subjected to arterial shear stress with the VEGF receptor tyrosine kinase inhibitor SU1498, or VEGFR2 neutralizing antiserum, led to increased apoptosis, demonstrating that the mechanoprotection from increased shear is mediated by VEGFR2. Taken together, these studies suggest that arterial flow induces VEGF-VEGFR2 autocrine-juxtacrine signaling, which is a previously unidentified mechanism for vascular EC survival in adult arterial blood vessels.
Chui TYP, Bissig D, Berkowitz BA, Akula JD. Refractive Development in the "ROP Rat". J Ophthalmol 2012;2012:956705.Abstract
Although retinopathy of prematurity (ROP) is clinically characterized by abnormal retinal vessels at the posterior pole of the eye, it is also commonly characterized by vascular abnormalities in the anterior segment, visual dysfunction which is based in retinal dysfunction, and, most commonly of all, arrested eye growth and high refractive error, particularly (and paradoxically) myopia. The oxygen-induced retinopathy rat model of ROP presents neurovascular outcomes similar to the human disease, although it is not yet known if the "ROP rat" also models the small-eyed myopia characteristic of ROP. In this study, magnetic resonance images (MRIs) of albino (Sprague-Dawley) and pigmented (Long-Evans) ROP rat eyes, and age- and strain-matched room-air-reared (RAR) controls, were examined. The positions and curvatures of the various optical media were measured and the refractive state (℞) of each eye estimated based on a previously published model. Even in adulthood (postnatal day 50), Sprague-Dawley and Long-Evans ROP rats were significantly myopic compared to strain-matched controls. The myopia in the Long-Evans ROP rats was more severe than in the Sprague-Dawley ROP rats, which also had significantly shorter axial lengths. These data reveal the ROP rat to be a novel and potentially informative approach to investigating physiological mechanisms in myopia in general and the myopia peculiar to ROP in particular.
Keating A, Pineda R. Trichosporon asahii keratitis in a patient with a type I Boston keratoprosthesis and contact lens. Eye Contact Lens 2012;38(2):130-2.Abstract
PURPOSE: The aim of the study was to report a case of Trichosporon asahii in a patient with a type I Boston keratoprosthesis and contact lens with review of the literature. METHODS: A case report and literature review are provided. RESULTS: A 70-year-old monocular South Asian man with light perception vision and dense corneal scarring from previously failed amniotic membrane grafting and one failed corneal transplant was evaluated for a keratoprosthesis for visual rehabilitation. Three months after undergoing uneventful implantation of a type I Boston keratoprosthesis and placement of a therapeutic contact lens, he was found on routine follow-up to have a corneal infiltrate that was culture positive for T. asahii. The fungal keratitis was successfully treated with topical amphotericin B and oral ketoconazole. CONCLUSIONS: Contact lens wear is a known risk factor for fungal keratitis. Trichosporon is an uncommon agent of fungal keratitis. We report the first known case of fungal keratitis caused by T.asahii in a patient with a keratoprosthesis and contact lens.
Huynh N, Stemmer-Rachamimov AO, Swearingen B, Cestari DM. Decreased vision and junctional scotoma from pituicytoma. Case Rep Ophthalmol 2012;3(2):190-6.Abstract
Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient's vision improved.

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