September 2017

Mueller SK, Miyake MM, Lefebvre DR, Freitag SK, Bleier BS. Long-term impact of endoscopic orbital decompression on sinonasal-specific quality of life. Laryngoscope 2018;128(4):785-788.Abstract
OBJECTIVE: Endoscopic orbital decompression (EOD) is the workhorse surgical intervention for severe thyroid eye disease in Graves disease. Although EOD is a safe and effective procedure, the objective of this study is to determine the impact of orbital decompression on long-term sinonasal-pecific quality of life. METHODS: Retrospective study of 27 patients who underwent EOD by a single surgeon. The primary endpoint was change in preoperative 22-item Sinonasal Outcomes Test (SNOT-22) score at a minimum of 1 year. The secondary endpoint was to determine whether the performance of septoplasty for surgical access in patients without nasal obstruction impacted domain 1 (i.e., rhinologic domain) and total SNOT-22 scores. RESULTS: The mean follow-up was 25.7 ± 11.4 months. Domain 1 scores significantly increased at the first postoperative visit (P ≤ 0.01) and returned to baseline values between 1 and 3 months. At 1 year, significant improvements in both total score and domain 4 and 5 (psychological and sleep dysfunction, respectively) scores were seen (P < 0.01 for all scores). Septoplasty was not associated with a significant change in SNOT-22 score at 1 year (P = 0.48). CONCLUSION: Endoscopic orbital decompression is associated at 1 year with a significant improvement in sinonasal-specific quality of life, which is driven by the psychological and sleep dysfunction domains. Adjunctive septoplasty has no significant impact on SNOT-22 scores. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:785-788, 2018.
Lundgren P, Hård A-L, Wilde Å, Löfqvist C, Smith LEH, Hellström A. Implementing higher oxygen saturation targets reduced the impact of poor weight gain as a predictor for retinopathy of prematurity. Acta Paediatr 2018;107(5):767-773.Abstract
AIM: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden. METHODS: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool. RESULTS: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016. CONCLUSION: After the SpO target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops.
González-Andrades M, Mata R, González-Gallardo MDC, Medialdea S, Arias-Santiago S, Martínez-Atienza J, Ruiz-García A, Pérez-Fajardo L, Lizana-Moreno A, Garzón I, Campos A, Alaminos M, Carmona G, Cuende N. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open 2017;7(9):e016487.Abstract
INTRODUCTION: There is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour. METHODS AND ANALYSIS: This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed. ETHICS AND DISSEMINATION: The trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION: CT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).
Iao TWU, Rong SS, Ling AN, Brelén ME, Young AL, Chong KKL. Electrophysiological Studies in Thyroid Associated Orbitopathy: A Systematic Review. Sci Rep 2017;7(1):12108.Abstract
Dysthyroid optic neuropathy (DON) is the commonest cause of blindness in thyroid associated orbitopathy (TAO). While diagnosis remains clinical, objective tests for eyes with early or equivocal findings are lacking. Various electrophysiological studies (EPS) have been reported, yet the types and parameters useful for DON remain inconclusive. We performed a systematic literature search in MEDLINE, EMBASE and the Cochrane databases via the OVID platform up to August 20, 2017. 437 records were identified for screening and 16 original studies (1327 eyes, 787 patients) were eligible for review. Pattern visual evoked potential (pVEP) was the most frequently studied EPS. Eyes of TAO patients with DON showed delayed P100 latencies, decreased P100 amplitudes or delayed N75 latencies during pVEP, compared to those without or healthy controls. Due to study heterogeneity, no quantitative analysis was possible. This review highlights the most common type (pVEP) and useful parameters (P100 latency and amplitude) of EPS, and supports further research on them using standardized testing conditions.
Wolfe JM. Visual Attention: Size Matters. Curr Biol 2017;27(18):R1002-R1003.Abstract
When searching real-world scenes, human attention is guided by knowledge of the plausible size of target object (if an object is six feet tall, it isn't your cat). Computer algorithms typically do not do this, but perhaps they should.
Hark LA, Katz JL, Myers JS, Waisbourd M, Johnson D, Pizzi LT, Leiby BE, Fudemberg SJ, Mantravadi AV, Henderer JD, Zhan T, Molineaux J, Doyle V, Divers M, Burns C, Murchison AP, Reber S, Resende A, Bui TDV, Lee J, Crews JE, Saaddine JB, Lee PP, Pasquale LR, Haller JA. Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Methods and Screening Results. Am J Ophthalmol 2017;181:114-124.Abstract
PURPOSE: To describe methodology and screening results from the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study. DESIGN: Screening program results for a prospective randomized clinical trial. METHODS: Individuals were recruited who were African-American, Hispanic/Latino, or Asian over age 40 years; white individuals over age 65 years; and any ethnicity over age 40 years with a family history of glaucoma or diabetes. Primary care offices and Federally Qualified Health Centers were used for telemedicine (Visit 1). Two posterior fundus photographs and 1 anterior segment photograph were captured per eye in each participant, using a nonmydriatic, autofocus, hand-held fundus camera (Volk Optical, Mentor, Ohio, USA). Medical and ocular history, family history of glaucoma, visual acuity, and intraocular pressure measurements using the ICare rebound tonometer (ICare, Helsinki, Finland) were obtained. Images were read remotely by a trained retina reader and a glaucoma specialist. RESULTS: From April 1, 2015, to February 6, 2017, 906 individuals consented and attended Visit 1. Of these, 553 participants were female (61.0%) and 550 were African-American (60.7%), with a mean age of 58.7 years. A total of 532 (58.7%) participants had diabetes, and 616 (68%) had a history of hypertension. During Visit 1, 356 (39.3%) participants were graded with a normal image. Using image data from the worse eye, 333 (36.8%) were abnormal and 155 (17.1%) were unreadable. A total of 258 (28.5%) had a suspicious nerve, 62 (6.8%) had ocular hypertension, 102 (11.3%) had diabetic retinopathy, and 68 (7.5%) had other retinal abnormalities. CONCLUSION: An integrated telemedicine screening intervention in primary care offices and Federally Qualified Health Centers detected high rate of suspicious optic nerves, ocular hypertension, and retinal pathology.
Bourne RRA, Flaxman SR, Braithwaite T, Cicinelli MV, Das A, Jonas JB, Keeffe J, Kempen JH, Leasher J, Limburg H, Naidoo K, Pesudovs K, Resnikoff S, Silvester A, Stevens GA, Tahhan N, Wong TY, Taylor HR, Taylor HR. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health 2017;5(9):e888-e897.Abstract
BACKGROUND: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. METHODS: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). FINDINGS: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9-65·4) were blind (crude prevalence 0·48%; 80% UI 0·17-0·87; 56% female), 216·6 million (80% UI 98·5-359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34-4·89; 55% female), and 188·5 million (80% UI 64·5-350·2) had mild visual impairment (2·57%, 80% UI 0·88-4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1-1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9-997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9-57·3) in 1990 to 36·0 million (80% UI 12·9-65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (-36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3-270·0) in 1990 to 216·6 million (80% UI 98·5-359·1) in 2015. INTERPRETATION: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. FUNDING: Brien Holden Vision Institute.
Nocera AL, Miyake MM, Seifert P, Han X, Bleier BS. Exosomes mediate interepithelial transfer of functional P-glycoprotein in chronic rhinosinusitis with nasal polyps. Laryngoscope 2017;127(9):E295-E300.Abstract
OBJECTIVE: P-glycoprotein (P-gp) drives type-2 helper T-cell inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) through unknown posttranslational mechanisms of overexpression. A recent randomized clinical trial demonstrated that inhibition of P-gp was as effective as oral steroids and biologics in treating CRSwNP. Exosomes are 30- to 150-nm vesicles capable of intercellular membrane protein transfer. The aims of this study were 1) to determine whether CRSwNP mucus exosomes are enriched with P-gp, and 2) whether exosomal P-gp can be functionally transferred to autologous epithelial cells as a putative mechanism for the proinflammatory overexpression of P-gp in CRSwNP. STUDY DESIGN: Institutional review board-approved study in CRSwNP and control patients (n = 10 per group). METHODS: P-gp content of purified mucus exosomes was characterized by transmission electron microscopy and enzyme-linked immunosorbent assay. Epithelial transfer of exosomal P-gp was determined by time-lapse fluorescent microscopy and calcein acetoxymethylester functional P-gp assay. RESULTS: CD63+/P-gp+ exosomes were detected in both groups. P-gp was significantly enriched in CRSwNP exosomes relative to control (median 198.5; interquartile range 123.6-270.5 vs. 74.4; 41.3-95.0 pcg P-gp/10(9) exosomes, P = 0.002). Exosomes were absorbed by epithelial cells within 10 minutes, resulting in a significant increase in P-gp activity in CRSwNP patients relative to control (P = 0.006). CONCLUSION: Here we demonstrate the presence and P-gp enrichment of mucus-derived exosomes, or rhinosomes, in CRSwNP. These rhinosomes are capable of rapid intercellular transfer of P-gp, leading to increased P-gp function within recipient cells. This represents a novel mechanism for maintaining P-gp overexpression in CRSwNP, and more generally for interepithelial transfer of other proteins between mucosal epithelial cells. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E295-E300, 2017.
Wang JC, Finn AP, Grotting LA, Sobrin L. Acute Zonal Occult Outer Retinopathy Associated With Retrobulbar Optic Neuritis. J Neuroophthalmol 2017;37(3):287-290.Abstract
A 17-year-old girl presented with unilateral retrobulbar optic neuritis as well as bilateral funduscopic findings and outer retinal dysfunction suggestive of acute zonal occult outer retinopathy (AZOOR). Fundus autofluorescence abnormalities, visual field loss, and electroretinographic changes were supportive of bilateral AZOOR. MRI was consistent with the diagnosis of clinically isolated syndrome (CIS), which is defined as a central nervous system demyelinating event that may herald the onset of multiple sclerosis (MS). While AZOOR previously has been linked to MS and demyelinating white matter lesions in the brain, our case seems unique due to concurrent development of AZOOR and retrobulbar optic neuritis as a CIS.
Heidary G. Neuro-Ophthalmic Manifestations of Pediatric Neurodegenerative Disease. J Neuroophthalmol 2017;37 Suppl 1:S4-S13.Abstract
The topic of pediatric neurodegenerative disease is broad and ever expanding. Children who suffer from neurodegenerative disease often have concomitant visual dysfunction. Neuro-ophthalmologists may become involved in clinical care to identify corroborating eye findings when a specific condition is suspected, to monitor for disease progression, and in some cases, to assess treatment efficacy. Ophthalmic findings also may be the harbinger of a neurodegenerative process so a keen awareness of the possible manifestations of these conditions is important. The purpose of this review is to highlight common examples of the neuro-ophthalmic manifestations of pediatric neurodegenerative disease using a case-based approach in an effort to provide a framework for approaching these complex patients.
Tischfield MA, Robson CD, Gilette NM, Chim SM, Sofela FA, DeLisle MM, Gelber A, Barry BJ, MacKinnon S, Dagi LR, Nathans J, Engle EC. Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell 2017;42(5):445-461.e5.Abstract
Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions that influence tissue-specific angiogenesis in mammals.
Mishra A, Browning D, Haviland MJ, Jackson ML, Luff D, Meyer EC, Talcott K, Kloek CE. Communication Skills Training in Ophthalmology: Results of a Needs Assessment and Pilot Training Program. J Surg Educ 2017;Abstract
OBJECTIVE: To conduct a needs assessment to identify gaps in communication skills training in ophthalmology residency programs and to use these results to pilot a communication workshop that prepares residents for difficult conversations. DESIGN: A mixed-methods design was used to perform the needs assessment. A pre-and postsurvey was administered to workshop participants. SETTING: Mass Eye and Ear Infirmary, Harvard Medical School (HMS), Department of Ophthalmology. PARTICIPANTS: HMS ophthalmology residents from postgraduate years 2-4 participated in the needs assessment and the workshop. Ophthalmology residency program directors in the United States participated in national needs assessment. METHODS: Ophthalmology program directors across the United States were queried on their perception of resident communication skills training through an online survey. A targeted needs assessment in the form of a narrative exercise captured resident perspectives on communication in ophthalmology from HMS residents. A group of HMS residents participated in the pilot workshop and a pre- and postsurvey was administered to participants to assess its effectiveness. RESULTS: The survey of program directors yielded a response rate of 40%. Ninety percent of respondents agreed that the communication skills training in their programs could be improved. Fifteen of 24 residents (62%) completed the needs assessment. Qualitative analysis of the narrative material revealed four themes; (1) differing expectations, (2) work role and environment, (3) challenges specific to ophthalmology, and (4) successful strategies adopted. Nine residents participated in the workshop. There was a significant improvement post-workshop in resident reported scores on their ability to manage their emotions during difficult conversations (p = 0.03). CONCLUSIONS: There is an opportunity to improve communication skills training in ophthalmology residency through formalized curriculum.
Tsikata E, Vercellin Verticchio AC, Falkenstein I, Poon LY-C, Brauner S, Khoueir Z, Miller JB, Chen TC. Volumetric Measurement of Optic Nerve Head Drusen Using Swept-Source Optical Coherence Tomography. J Glaucoma 2017;26(9):798-804.Abstract
PURPOSE: To describe new software tools for quantifying optic nerve head drusen volume using 3-dimensional (3D) swept-source optical coherence tomography (SS-OCT) volumetric scans. MATERIALS AND METHODS: SS-OCT was used to acquire raster volume scans of 8 eyes of 4 patients with bilateral optic nerve head drusen. The scans were manually segmented by 3 graders to identify the drusen borders, and thereafter total drusen volumes were calculated. Linear regression was performed to study the relationships between drusen volume, retinal nerve fiber layer thickness, and Humphrey visual field mean deviation. RESULTS: In the 8 study eyes, drusen volumes ranged between 0.24 to 1.05 mm. Visual field mean deviation decreased by ∼20 dB per cubic millimeter increase in drusen volume, and the coefficient of correlation of the linear regression was 0.92. In this small patient series, visual field defects were detected when drusen volume was larger than about 0.2 mm. CONCLUSIONS: Software tools have been developed to quantify the size of OHND using SS-OCT volume scans.

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