Drokhlyansky E, Göz Aytürk D, Soh TK, Chrenek R, O'Loughlin E, Madore C, Butovsky O, Cepko CL. The brain parenchyma has a type I interferon response that can limit virus spread. Proc Natl Acad Sci U S A 2017;114(1):E95-E104.Abstract

The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.

Fu Z, Meng SS, Burnim SB, Smith LEH, Lo AC. Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity. Clin Exp Ophthalmol 2017;45(5):529-538.Abstract
BACKGROUND: Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. METHODS: Mouse pups were exposed to 75% oxygen for 5 days and returned to room air for another 5 days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. RESULTS: Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. CONCLUSIONS: Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature.
Kobashi H, Kamiya K, Shimizu K. Randomized Comparison Between Rebamipide Ophthalmic Suspension and Diquafosol Ophthalmic Solution for Dry Eye After Penetrating Keratoplasty. J Ocul Pharmacol Ther 2017;33(1):13-18.Abstract

PURPOSE: To compare the ocular surfaces of patients treated with rebamipide (REB) ophthalmic suspension or diquafosol (DQS) ophthalmic solution for dry eye syndrome after penetrating keratoplasty (PK). METHODS: A total of 40 eyes of 40 patients who had dry eyes after undergoing PK were enrolled and randomly divided into an REB group and a DQS group. Both REB and DQS groups used each eye drop four times. The tear breakup time (TBUT), corneal fluorescein staining scores, and dry eye-related quality-of-life score (DEQS) were evaluated before treatment, 2 weeks after start of treatment and 4 weeks after start of treatment. RESULTS: We found a significant improvement in TBUT (P < 0.001, Dunnett's test) and fluorescein scores (P < 0.001) 4 weeks after treatment in the REB group. Similar results were obtained in the DQS group (P < 0.001 and P = 0.01, respectively). No significant improvements in DEQS were found 4 weeks after treatment in each group (P = 0.15 and P = 0.63, analysis of variance, respectively). No significant differences were seen in these variables and in the changes between the groups after treatment. CONCLUSIONS: REB and DQS may be effective for the management of dry eye syndrome after PK in terms of ocular surface findings. In our study, effects of REB appear to be equivalent to those of DQS in the patients.

Wu D, Qian T, Nakao T, Xu J, Liu Z, Sun X, Chu Y, Hong J. Medically uncontrolled conjunctival pyogenic granulomas: correlation between clinical characteristics and histological findings. Oncotarget 2017;8(2):2020-2024.Abstract

BACKGROUND: Conjunctival pyogenic granulomas are commonly seen after ocular surgeries or at an ocular wound site. The aim of this study is to describe a novel histological classification for medically uncontrolled conjunctival pyogenic granulomas (MUCPG), and to explore whether the diversity in clinical features correlates to different histological subtypes of MUCPG. METHODS: This is an observational cross-section case series. We reviewed 46 consecutive patients with conjunctival pyogenic granulomas who did not respond to topical corticosteroids and underwent surgical excision from January 1, 2006 through December 31, 2015. Clinical features and histological findings were presented and analyzed. RESULTS: Ocular surgery, accidental injury, and chalazion were the main predisposing causes of MUCPG. The lesions tended to occur unilaterally on the bulbar conjunctiva. Forty patients (87%) presented an enrichment of inflammatory cells and proliferated capillaries in their pathological sections (inflammatory pattern). Six patients (13%) showed relatively few inflammatory cells and capillaries within fibrous stroma (fibrous pattern). Patients with the inflammatory pattern were older (p = 0.025) and tended to be located in bulbar conjunctiva (p = 0.002). The predisposing causes were also different between two histological subtypes (p = 0.007). CONCLUSIONS: We found the correlation between clinical presentation and histological subtypes in patients with MUCPG, indicating this disease may need a new classification scheme.

Homer N, Yoon MK. Evaluation of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Fellowship Program Website Content and Quality. Ophthal Plast Reconstr Surg 2017;33(6):471-473.Abstract
PURPOSE: The qualities that applicants value in the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellowship programs have been studied, but the availability of this information on program websites has not yet been reviewed. The authors evaluated the availability of resident-valued ASOPRS fellowship program information on the Internet. METHODS: The authors performed an Internet search of the 53 ASOPRS fellowship program websites and evaluated websites for 20 characteristics of interest to ASOPRS fellowship applicants such as teaching faculty, program description, rotation schedule, operative cases, and interview information. RESULTS: Of the 53 ASOPRS fellowship programs, 43 (81.1%) had a fellowship program-dedicated website. The fellowship websites contained a mean 7.6 characteristics (38.1%, range 0-15). Faculty listing, program description, and case diversity were the most commonly included data (74.4%, 72.1%, and 69.8%, respectively). Fellow selection process, interview information, and graduate job placement were least commonly included (7.0%, 2.3%, and 0.0%, respectively). There was no significant difference in website inclusiveness based on fellowship region or faculty number. Programs affiliated with an ophthalmology residency were more complete than those that were not (40.3% vs. 20.0%, p = 0.0098). CONCLUSIONS: This review found that most programs had websites and contained a reasonable number of characteristics. However, applicant-valued information regarding surgical volume, procedure variety, application information, and postgraduate employment history were often missing. American Society of Ophthalmic Plastic and Reconstructive Surgery fellowship programs may improve match outcomes by providing and enhancing program websites with details that their applicants seek.
Dagi Glass LR, Lawrence DP, Jakobiec FA, Freitag SK. Conjunctival Melanoma Responsive to Combined Systemic BRAF/MEK Inhibitors. Ophthal Plast Reconstr Surg 2017;33(5):e114-e116.Abstract
This report demonstrates a unique case of conjunctival melanoma harboring a BRAF V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While systemic therapy would not be appropriate in patients with local disease alone, it may act therapeutically in cases of higher stage ocular surface and eyelid melanoma.
Hamrah P, Qazi Y, Shahatit B, Dastjerdi MH, Pavan-Langston D, Jacobs DS, Rosenthal P. Corneal Nerve and Epithelial Cell Alterations in Corneal Allodynia: An In Vivo Confocal Microscopy Case Series. Ocul Surf 2017;15(1):139-151.Abstract

PURPOSE: To investigate morphological changes of the corneal epithelium and subbasal nerves in patients with corneal allodynia using in vivo confocal microscopy (IVCM). DESIGN: Case-control study of patients with corneal allodynia and healthy controls. METHODS: Ten eyes of six patients were diagnosed with corneal allodynia at a single center and compared to fifteen healthy eyes. IVCM of the central cornea was performed on all subjects and controls. Images were retrospectively analyzed numbers of total corneal subbasal nerves, main trunks and branches, total nerve length and density, nerve branching, and tortuosity, superficial and basal epithelial cell densities, and superficial epithelial cell size. RESULTS: Corneal allodynia was seen in patients with dry eye disease, recurrent corneal erosion syndrome, exposure to ultraviolet radiation, and Accutane use. Compared to controls, patients with corneal allodynia had a significant decrease in the total numbers of subbasal nerves (P=.014), nerve branches (P=.006), total nerve length (P=.0029), total nerve density (P=.0029) and superficial and basal epithelial cell densities (P=.0004, P=.0036) with an increase in superficial epithelial cell size (P=.016). There were no statistically significant differences in the number of subbasal nerve main trunks (P=.09), nerve branching (P=.21), and nerve tortuosity (P=.05). CONCLUSIONS: Corneal IVCM enables near-histological visualization and quantification of the cellular and neural changes in corneal allodynia. Regardless of etiology, corneal allodynia is associated with decreased corneal epithelial cell densities, increased epithelial cell size, and decreased numbers and lengths of subbasal nerves despite an unremarkable slit-lamp examination. Therefore, IVCM may be useful in the management of patients with corneal allodynia.

Nihalani BR, VanderVeen DK. Benchmarks for outcome indicators in pediatric cataract surgery. Eye (Lond) 2017;31(3):417-421.Abstract

PurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3±4.6 years and mean follow-up duration was 3.7±2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96% (n=124 eyes, mean patient age: 8.3±4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3±1.1 D and mean absolute PE was 0.9±0.7 D. PE was within ±0.5 D in 43.0%, ±1.0 D in 66%, and ±2.0 D in 95% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.

Mikolajczak J, Zimmermann H, Kheirkhah A, Kadas EM, Oberwahrenbrock T, Muller R, Ren A, Kuchling J, Dietze H, Prüss H, Paul F, Hamrah P, Brandt AU. Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density. Mult Scler 2017;23(14):1847-1853.Abstract
BACKGROUND: Many studies in multiple sclerosis (MS) have investigated the retina. Little, however, is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response to environmental stimuli. OBJECTIVE: This study aims to investigate the effect of MS on corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM). METHODS: We measured the corneal nerve fibre and dendritic cell density in 26 MS patients and matched healthy controls using a Heidelberg Retina Tomograph with cornea module. Disease severity was assessed with the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale, visual acuity and retinal optical coherence tomography. RESULTS: We observed significant reduction in total corneal nerve fibre density in MS patients compared to controls. Dendritic cell density was similar in both groups. Reduced total nerve fibre density was associated with worse clinical severity but not with previous clinical trigeminal symptoms, retinal neuro-axonal damage, visual acuity or disease duration. CONCLUSION: Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.
Avery RA, Katowitz JA, Fisher MJ, Heidary G, Dombi E, Packer RJ, Widemann BC, Widemann BC. Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Multidisciplinary Recommendations for Care. Ophthalmology 2017;124(1):123-132.Abstract

TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. CLINICAL RELEVANCE: Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome. METHODS: Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials. RESULTS: In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. CONCLUSIONS: This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.

Al-Haddad CE, Abdulaal M, Al-Moujahed A, Ervin A-M, Ismail K. Fornix-Based Versus Limbal-Based Conjunctival Trabeculectomy Flaps for Glaucoma: Findings From a Cochrane Systematic Review. Am J Ophthalmol 2017;174:33-41.Abstract

PURPOSE: To compare effectiveness of fornix- and limbal-based conjunctival flaps in trabeculectomy surgery. DESIGN: Systematic review. METHODS: Setting: CENTRAL, MEDLINE, LILACS, ISRCTN registry,, WHO, and ICTRP were searched to identify eligible randomized controlled trials (RCTs). STUDY POPULATION: RCTs in which benefits and complications of fornix- vs limbal-based trabeculectomy for glaucoma were compared in adult glaucoma patients. OBSERVATION PROCEDURE: We followed Cochrane methodology for data extraction. MAIN OUTCOME MEASURES: Proportion of failed trabeculectomies at 24 months, defined as the need for repeat surgery or uncontrolled intraocular pressure (IOP) >22 mm Hg, despite topical/systemic medications. RESULTS: The review included 6 trials with a total of 361 participants, showing no difference in effectiveness between fornix-based vs limbal-based trabeculectomy surgery, although with a high level of uncertainty owing to low event rates. In the fornix-based and limbal-based surgery, mean IOP at 12 months was similar, with ranges of 12.5-15.5 mm Hg and 11.7-15.1 mm Hg, respectively. Mean difference was 0.44 mm Hg (95% CI -0.45 to 1.33) and 0.86 mm Hg (95% CI -0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Mean number of postoperative glaucoma medications was similar between the 2 groups. Mean difference was 0.02 (95% CI -0.15 to 0.19) at 12 months. As far as postoperative complications, an increased risk of shallow anterior chamber was observed in the limbal-based group. CONCLUSION: Similar efficacy of trabeculectomy surgery with respect to bleb failure or IOP control was observed in both types of conjunctival flap incisions. A significant difference was detected in the risk of postoperative shallow anterior chamber, which was increased in the limbal-based group.

Vodopivec I, Cestari DM, Rizzo JF. Management of Transient Monocular Vision Loss and Retinal Artery Occlusions. Semin Ophthalmol 2017;32(1):125-133.Abstract

Acute transient or permanent retinal occlusive disease requires prompt medical attention and can be an ophthalmological emergency. Central retinal artery occlusion leads to permanent and severe monocular visual loss in the majority of patients. Transient monocular vision loss leaves no permanent deficits, but requires the same level of clinical vigilance, as it portends possible future adverse events, including loss of vision and stroke. Acute treatment options remain limited, and secondary prevention of cerebral ischemic events is the mainstay of management. This article reviews the current evidence for managing patients with retinal ischemia.

PURPOSE: To determine the incidence of retinal redetachment due to proliferative vitreoretinopathy after open-globe trauma in smokers and nonsmokers. METHODS: A total of 892 patients comprising 893 open-globe injuries, in whom 255 eyes were diagnosed with a retinal detachment, and 138 underwent surgical repair were analyzed in a retrospective case-control study. Time to redetachment was examined using the Kaplan-Meier method and analysis of risk factors was analyzed using Cox proportional hazards modeling. RESULTS: Within one year after retinal detachment surgery, 47% (95% CI, 39-56%) of all 138 repaired retinas redetached because of proliferative vitreoretinopathy. Being a smoker was associated with a higher rate of detachment (adjusted hazard ratio 1.96, P = 0.01). As shown in previous studies, the presence of proliferative vitreoretinopathy at the time of surgery was also an independent risk factor for failure (adjusted hazard ratio 2.13, P = 0.005). Treatment with vitrectomy-buckle compared favorably to vitrectomy alone (adjusted hazard ratio 0.58, P = 0.04). Only 8% of eyes that redetached achieved a best-corrected visual acuity of 20/200 or better, in comparison to 44% of eyes that did not redetach (P < 0.001). CONCLUSION: Proliferative vitreoretinopathy is a common complication after the repair of retinal detachment associated with open-globe trauma, and being a smoker is a risk factor for redetachment. Further study is needed to understand the pathophysiologic mechanisms underlying this correlation.
Joseph A, Pasquale LR. Attributes Associated with Adherence to Glaucoma Medical Therapy and its Effects on Glaucoma Outcomes: An Evidence-Based Review and Potential Strategies to Improve Adherence. Semin Ophthalmol 2017;32(1):86-90.Abstract

The treatment paradigm in glaucoma classically starts with exhausting all medical therapy prior to proceeding with laser or incisional surgery, although laser-first and surgery-first strategies have been explored in randomized clinical trials. Although glaucoma drops are proven to work well to lower intraocular pressure, slow the conversion from ocular hypertension, and slow the progression of disease in early open angle glaucoma, adherence to treatment is likely optimum in the randomized clinical trials that support these claims. In real-world scenarios, medical therapy often fails and practitioners are forced to proceed with more invasive treatment modalities to slow the progression of this blinding disease. This review aims to take an evidence-based approach to study the risk factors for poor adherence in glaucoma patients, to determine whether poor adherence is, in fact, associated with worse outcomes, and to seek potential strategies to improve adherence in these patients.