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Bunker S, Holeniewska J, Vijay S, Dahlmann-Noor A, Khaw P, Ng Y-S, Shima D, Foxton R. Experimental glaucoma induced by ocular injection of magnetic microspheres. J Vis Exp 2015;(96)Abstract

Progress in understanding the pathophysiology, and providing novel treatments for glaucoma is dependent on good animal models of the disease. We present here a protocol for elevating intraocular pressure (IOP) in the rat, by injecting magnetic microspheres into the anterior chamber of the eye. The use of magnetic particles allows the user to manipulate the beads into the iridocorneal angle, thus providing a very effective blockade of fluid outflow from the trabecular meshwork. This leads to long-lasting IOP rises, and eventually neuronal death in the ganglion cell layer (GCL) as well as optic nerve pathology, as seen in patients with the disease. This method is simple to perform, as it does not require machinery, specialist surgical skills, or many hours of practice to perfect. Furthermore, the pressure elevations are very robust, and reinjection of the magnetic microspheres is not usually required unlike in some other models using plastic beads. Additionally, we believe this method is suitable for adaptation for the mouse eye.

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Cai S, Elze T, Bex PJ, Wiggs JL, Pasquale LR, Shen LQ. Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic. Curr Eye Res 2017;42(4):568-574.Abstract

PURPOSE: To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns. MATERIALS AND METHODS: For each of 16 previously identified VF loss patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10-20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test. RESULTS: 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often ≥ 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often < 0.7 among eyes representative of AT1 (no focal defect; p < 0.001) and AT2 (superior defect; p = 0.027), which was also associated with ptosis (p < 0.001). AT12 (temporal hemianopia) was associated with history of stroke (p = 0.022). AT11 (concentric peripheral defect) trended toward association with trial lens correction > 6D (p = 0.069). CONCLUSIONS: Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.

Campbell AA, Jakobiec FA, Rashid A, Dana R, Yoon MK. Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease. Ophthal Plast Reconstr Surg 2016;32(4):e89-92.Abstract

A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.

Campbell AA, Cunnane ME, Dunn GP, Gray ST, Lefebvre DR. Spontaneous Resorption of a Penetrating Orbital Bone Fracture Fragment. Ophthal Plast Reconstr Surg 2015;31(5):e123-5.Abstract

The authors describe a 20-year-old man who sustained multiple facial fractures in a high-speed motor vehicle crash, including a bone fragment from a skull base fracture that penetrated the orbital soft tissues superomedially. Serial CT scans documented spontaneous resorption over a 6-month period. While it is known that autologous bone grafts used in craniofacial reconstruction exhibit variable amounts of bone resorption, the complete resorption of an intraorbital fracture fragment has not been documented in the literature. His clinical care and the report of his case were undertaken in a fashion in accordance with the principles of the Health Insurance Portability and Accountability Act regulations.

Cao JH, Oray M, Cocho L, Foster SC. Rituximab in the Treatment of Refractory Noninfectious Scleritis. Am J Ophthalmol 2016;164:22-8.Abstract

PURPOSE: To describe the outcomes of the use of rituximab in the treatment of refractory noninfectious scleritis. DESIGN: Retrospective case series. METHODS: Review of the medical charts of patients with noninfectious scleritis refractory to conventional immunomodulatory therapy who were seen at the Massachusetts Eye Research and Surgery Institution between 2005 and 2015. The primary outcome measure in this study was steroid-free remission. Secondary outcomes were favorable response (decrease in scleritis activity score) and decrease in steroid dependence. RESULTS: There were 15 patients, with a mean follow-up duration of 34 months. Fourteen patients (93.3%) showed a clinical improvement, with 13 (86.6%) achieving a scleritis activity score of zero at 6 months. To date, 2 patients continue to enjoy durable drug-free remission (28 and 32 months follow-up). There was only 1 adverse effect recorded (infusion hypotension) requiring cessation of rituximab. CONCLUSION: Rituximab can be an effective treatment modality for recalcitrant noninfectious scleritis and, in some, can result in long-term durable drug-free remission.

Carniciu AL, Chou J, Leskov I, Freitag SK. Clinical Presentation and Bacteriology of Eyebrow Infections: The Massachusetts Eye and Ear Infirmary Experience (2008-2015). Ophthal Plast Reconstr Surg 2016;Abstract

PURPOSE: This study retrospectively reviews preseptal cellulitis and abscesses involving the eyebrow to elucidate the bacteriology and potential causative factors. METHODS: A retrospective chart review was conducted to identify patients who had been diagnosed with preseptal cellulitis or abscess involving the eyebrow at the Massachusetts Eye and Ear Infirmary between 2008 and 2015. Demographic, clinical, and microbiological data were collected. RESULTS: Eighty patients with eyebrow infections were identified, of whom 49 (61.3%) were female and 31 (38.7%) were male. The median age was 37 years (range 14-67 years). Eyebrow abscess was present in 54 cases (67.5%), while 26 cases (32.5%) were limited to preseptal cellulitis without abscess formation. Methicillin-resistant Staphylococcus aureus was found in 20 abscesses (39.2% of culture results), and methicillin-sensitive S. aureus was found in 12 abscesses (23.5% of culture results). Coagulase-negative staphylococci were present in 7 eyebrow abscesses (13.7% of culture results). Clinical history was remarkable for eyebrow hair removal (tweezing, waxing, threading, or shaving) in 17 cases (21.3%), manipulation of acne lesions ("popping," "picking," or "squeezing") in 6 cases (7.5%), and both brow hair removal and acne manipulation in 1 case (1.3%). CONCLUSIONS: There is a high incidence of methicillin-resistant Staphylococcus aureus in the bacteriology of eyebrow infections. Empirical antibiotic coverage for methicillin-resistant Staphylococcus aureus should be strongly considered in any patient with an eyebrow area abscess or preseptal cellulitis. Individuals who practice cosmetic eyebrow grooming should be encouraged to consider hygiene practices, which could reduce the risk of infection.

Carvalho LS, Vandenberghe LH. Promising and delivering gene therapies for vision loss. Vision Res 2015;111(Pt B):124-33.Abstract

The maturity in our understanding of the genetics and the pathogenesis of disease in degenerative retinal disorders has intersected in past years with a novel treatment paradigm in which a genetic intervention may lead to sustained therapeutic benefit, and in some cases even restoration of vision. Here, we review this prospect of retinal gene therapy, discuss the enabling technologies that have led to first-in-human demonstrations of efficacy and safety, and the road that led to this exciting point in time.

Carvalho LS, Vandenberghe LH. Understanding Cone Photoreceptor Cell Death in Achromatopsia. Adv Exp Med Biol 2016;854:231-6.Abstract

Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.

Castle MJ, Turunen HT, Vandenberghe LH, Wolfe JH. Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids. Methods Mol Biol 2016;1382:133-49.Abstract

More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina.

Cattaneo Z, Lega C, Gardelli C, Merabet LB, Cela-Conde CJ, Nadal M. The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: a TMS study. Neuroimage 2014;99:443-50.Abstract

To explain the biological foundations of art appreciation is to explain one of our species' distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants' a-priori inclination toward one or the other.

Cepko C, Punzo C. Cell metabolism: Sugar for sight. Nature 2015;522(7557):428-9.
Cepko C. Intrinsically different retinal progenitor cells produce specific types of progeny. Nat Rev Neurosci 2014;15(9):615-27.Abstract

Lineage studies conducted in the retina more than 25 years ago demonstrated the multipotency of retinal progenitor cells (RPCs). The number and types of cells produced by individual RPCs, even from a single time point in development, were found to be highly variable. This raised the question of whether this variability was due to intrinsic differences among RPCs or to extrinsic and/or stochastic effects on equivalent RPCs or their progeny. Newer lineage studies that have made use of molecular markers of RPCs, retrovirus-mediated lineage analyses of specific RPCs and live imaging have begun to provide answers to this question. RPCs that produce two postmitotic daughter cells - that is, terminally dividing RPCs - have been the most well characterized RPCs to date, and have been shown to produce specific types of daughter cells. In addition, recent studies have begun to shed light on the mechanisms that drive the temporal order in which retinal cells are born.

Cestari DM, Gaier ED, Bouzika P, Blachley TS, De Lott LB, Rizzo JF, Wiggs JL, Kang JH, Pasquale LR, Stein JD. Demographic, Systemic, and Ocular Factors Associated with Nonarteritic Anterior Ischemic Optic Neuropathy. Ophthalmology 2016;123(12):2446-2455.Abstract

OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for ≥2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had ≥1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean ± standard deviation (SD) follow-up of 7.8±3.1 years. The mean ± SD age for NAION cases at the index date was 64.0±9.2 years vs. 58.4±9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.

Cestari DM, Lessell S, Mantopoulos D. Early Diagnosis of Subclinical Interferon Alpha-Associated Optic Neuropathy Using Fluorescein Angiography. J Neuroophthalmol 2015;35(3):280-3.Abstract

We report a case of a 57-year-old man who presented with decreased visual acuity in the left eye secondary to nonarteritic anterior ischemic optic neuropathy (NAION) while on therapy with interferon-α for hepatitis C. Fundus fluorescein angiography revealed late leakage of both optic discs, consistent with bilateral disease. One week later, the patient developed clinical signs and symptoms consistent with NAION in the fellow eye. Fluorescein angiography may play an important role in identifying subclinical NAION in patients taking interferon-α.

Cestari DM, Arnold A. Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy?. J Neuroophthalmol 2016;36(3):329-33.
Chan KW, Deng L, Weissberg EM. Detection of Strabismus by Non-Health Care Professionals in an Ethnically Diverse Set of Images. JAMA Ophthalmol 2016;134(1):30-6.Abstract

IMPORTANCE: Understanding the criteria for when strabismus becomes detectable by non-health care professionals could influence the goals for determining the success of surgical intervention and how patients with such misalignments are counseled. OBJECTIVE: To examine the magnitude at which strabismus is detectable by lay observers in an ethnically diverse set of images. DESIGN, SETTING, AND PARTICIPANTS: Photographs of 12 ethnically diverse models (black, white, and Asian) were simulated to have strabismus from esotropia of 21 prism diopters (∆) to exotropia of 21∆. From July 1, 2007, to October, 1, 2008, images were presented to 120 non-health care professionals aged 21 years or older from the general community in Boston, Massachusetts, who were asked whether strabismus was present. Analysis was conducted from November 1, 2008, to March 31, 2009. MAIN OUTCOMES AND MEASURES: The threshold angle for detecting strabismus to enable 70% of lay observers to make a positive determination whether strabismus is present. RESULTS: In white and black models, the threshold allowing a 70% positive detection rate was higher for esotropia than for exotropia (P < .001 for both). For white models, the threshold was 23.2∆ (95% CI, 21.0∆ to 26.5∆) for esotropia and 13.5∆ (95% CI, 12.5∆ to 14.6∆) for exotropia. For black models, the threshold was 20.8∆ (95% CI, 19.2∆ to 22.2∆) for esotropia and 16.3∆ (95% CI, 15.5∆ to 17.2∆) for exotropia. Asian models showed an opposite trend, with the threshold allowing a 70% positive detection rate for esotropia (14.3∆; 95% CI, 13.2∆ to 15.7∆) being lower than that for exotropia (20.9∆; 95% CI, 18.0∆ to 24.6∆) (P < .001). CONCLUSIONS AND RELEVANCE: Esotropia was easier for lay observers to detect than exotropia in Asian models, and exotropia was easier to detect than esotropia in white and black models. This information should be considered when managing patients who have concerns about the social significance of their strabismus. Future studies should include diverse individuals and make an effort to account for individual factors that may alter the perception of strabismus.

Chan CY, Papakostas TD, Vavvas D. Evaluation of choroidal thickness among patients with oculocutaneous albinism. Br J Ophthalmol 2014;98(8):1135.
Chang Y-H, Melvin P, Dagi LR. Goal-determined metrics to assess outcomes ofexotropia surgery. J AAPOS 2015;Abstract

PURPOSE: To present a goal-determined methodology for monitoring outcomes after surgery for exotropia. METHODS: The goal-determined metric required surgeons to rank four possible goals preoperatively: (1) binocular potential, (2) restoration of eye contact, (3) diplopia control; and (4) torticollis management. Potential preoperative risk factors were noted. Goal-specific outcomes criteria were applied to the latest sensory-motor examination, 2-6 months after surgery. The medical records of patients who underwent surgery from 2007 to 2012 were retrospectively reviewed with respect to the goal-directed metric. RESULTS: A total of 852 patients were evaluated in the study period: 411 for restoration of eye contact; 347 for binocular potential; 78 for diplopia resolution; and16 for torticollis management. Excellent (62%) or good (16%) outcomes were achieved in 78%. Procedures to resolve diplopia (OR, 6.56; 95% CI, 3.39-12.68) and to restore eye contact (OR, 3.74; 95% CI, 2.65-5.29) were more likely to result in excellent outcomes than procedures to improve binocular potential. Simultaneous surgery for dissociated vertical deviation (OR, 0.38; 95% CI, 0.16-0.92) and preoperative near deviation ≥50(Δ) (OR, 0.27; 95% CI, 0.17-0.42) limited likelihood of an excellent outcome. Outcomes monitored by simultaneous rather than alternate prism and cover test were more likely graded excellent (OR, 5.16; 95% CI, 3.50-7.62). Applying motor criteria from the binocular potential goal to the entire cohort diminished putative outcomes (P < 0.001). CONCLUSIONS: Goal-determined metric monitoring outcomes of exotropia surgery provides outcomes germane to the reason for intervention, enables analysis of risk factors affecting outcomes, and facilitates reporting on heterogeneous populations.

Chao W, Belmonte C, Benitez Del Castillo J, Bron A, Dua H, Nichols K, Novack G, Schrader S, Willcox M, Wolffsohn J, Sullivan DA. Report of the Inaugural Meeting of the TFOS i2 = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment (London, United Kingdom, March 21, 2015). Ocul Surf 2016;Abstract

In March 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting.

Charles NC, Jakobiec FA, Patel P. Periorbital Dermoid Cyst With Unique Trichilemmal Differentiation. Ophthal Plast Reconstr Surg 2016;Abstract

The authors describe a 4-year-old girl presenting with a 2-year history of a superomedial eyelid "bump" that appeared cystic on MRI. The clinical diagnosis was dermoid cyst, possibly of conjunctival origin. Following excision, histology showed a cyst that contained keratin and lanugo hairs in its lumen with sebaceous glands and chronic inflammation in its fibrous wall. An unanticipated finding was the presence of a trichilemmal (pilar) variety of epithelial lining that stained positively for calretinin, an immunostain that identifies trichilemmal epithelium. To the authors' knowledge this is the first case of a dermoid cyst with trichilemmal lining. This study was conducted in compliance with the rules and regulations of the Health Insurance Portability and Accountability Act and in conformity with the Oslo declaration.

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