December 2015

Berry RH, Qu J, John SWM, Howell GR, Jakobs TC. Synapse Loss and Dendrite Remodeling in a Mouse Model of Glaucoma. PLoS One 2015;10(12):e0144341.Abstract

It has been hypothesized that synaptic pruning precedes retinal ganglion cell degeneration in glaucoma, causing early dysfunction to retinal ganglion cells. To begin to assess this, we studied the excitatory synaptic inputs to individual ganglion cells in normal mouse retinas and in retinas with ganglion cell degeneration from glaucoma (DBA/2J), or following an optic nerve crush. Excitatory synapses were labeled by AAV2-mediated transfection of ganglion cells with PSD-95-GFP. After both insults the linear density of synaptic inputs to ganglion cells decreased. In parallel, the dendritic arbors lost complexity. We did not observe any cells that had lost dendritic synaptic input while preserving a normal or near-normal morphology. Within the temporal limits of these observations, dendritic remodeling and synapse pruning thus appear to occur near-simultaneously.

Bleier BS, Castelnuovo P, Battaglia P, Turri-Zanoni M, Dallan I, Metson R, Sedaghat AR, Stefko TS, Gardner PA, Snyderman CH, Nogueira JF, Ramakrishnan VR, Muscatello L, Lenzi R, Freitag S. Endoscopic endonasal orbital cavernous hemangioma resection: global experience in techniques and outcomes. Int Forum Allergy Rhinol 2015;Abstract

BACKGROUND: Endoscopic orbital surgery represents the next frontier in endonasal surgery. The current literature is largely composed of small, heterogeneous, case series with little consensus regarding optimal techniques. The purpose of this study was to combine the experience of multiple international centers to create a composite of the global experience on the endoscopic management of a single type of tumor, the orbital cavernous hemangioma (OCH). METHODS: This was a retrospective study of techniques for endoscopic OCH resection from 6 centers on 3 continents. Only primary data from strictly endoscopic resection of OCHs were included. Responses were analyzed to qualitatively identify points of both consensus and variability among the different groups. RESULTS: Data for a total of 23 patients, 10 (43.5%) male and 13 (56.5%) female were collected. The majority of lesions were intraconal (60.9%). The mean ± standard deviation (SD) surgical time was 150.7 ± 75.0 minutes with a mean blood loss of 82.7 ± 49.6 mL. Binarial approaches (26.1%) were used exclusively in the setting of intraconal lesions, which were associated with a higher rate of incomplete resection (31.3%), postoperative diplopia (25.0%), and the need for reconstruction (37.5%) than extraconal lesions. Orthotropia and symmetric orbital appearance were achieved in 60.9% and 78.3% of cases, respectively. CONCLUSION: Extraconal lesions were managed similarly; however, greater variability was evident for intraconal lesions. These included the laterality and number of hands in the approach, methods of medial rectus retraction, and the need for reconstruction. The increased technical complexity and disparity of techniques in addressing intraconal OCHs suggests that continued research into the optimal management of this subclass of lesions is of significant priority.

Boonsopon S, Maghsoudlou A, Kombo NE, Foster SC. A therapeutic trial of valganciclovir in patients with uveitis and positive Epstein-Barr virus early antigen D IgG titers. Eur J Ophthalmol 2015;26(1):30-5.Abstract

PURPOSE: To evaluate the effectiveness of a therapeutic trial of valganciclovir in patients with uveitis with positive Epstein-Barr virus early antigen D immunoglobulin G titers (EBV EA-D). METHODS: We performed a retrospective chart review of 14 patients at the Massachusetts Eye Research and Surgery Institution who had uveitis with positive EBV EA-D but negative studies for all other causes of uveitis and were treated with valganciclovir 450 mg twice a day or valganciclovir 900 mg twice a day between January 2010 and August 2014. RESULTS: Nine of 14 patients, who had presumed EBV reactivation with associated intraocular inflammation, were successfully treated with valganciclovir: 3 of these were treated with valganciclovir 450 mg twice a day and 6 were treated with valganciclovir 900 mg twice a day. Five of 14 patients failed to respond to valganciclovir with persistent inflammation after at least 2 weeks of valganciclovir therapy, and were subsequently treated with immunomodulatory therapy to control inflammation. CONCLUSIONS: Uveitis can be caused by EBV infection/reactivation. A therapeutic trial with valganciclovir 450 mg twice a day for 1 month in patients with uveitis with positive EBV EA antibody may be beneficial.

Conlin PR, Asefzadeh B, Pasquale LR, Selvin G, Lamkin R, Cavallerano AA. Accuracy of a technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant ocular diseases. Br J Ophthalmol 2015;99(12):1622-7.Abstract

BACKGROUND/AIMS: Digital retinal imaging using store-and-forward technology is used to screen for diabetic retinopathy (DR). Its usefulness in detecting non-diabetic eye diseases is uncertain. We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions. METHODS: We conducted a prospective, observational study with two parallel evaluations. Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the same day. A subset of participants with normal baseline exams (n=72) had follow-up exams 1 year later. We measured the level of agreement for referable ocular findings. RESULTS: Agreement for referable ocular findings was moderate (n=389, agreement: 77%; κ: 0.55), due in part to ungradable exams (22%). However, about half of the ungradable exams had findings that warranted referral. There was substantial agreement for follow-up exams (n=72, agreement: 93%; κ: 0.63). Among all gradable exams (n=303), the TAE exam had 86% sensitivity and 84% specificity for referable ocular findings, with high agreement (≥94%) for DR and other major ocular diagnoses. CONCLUSIONS: There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes. Ungradable exams were a frequent marker of ocular pathology. Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions.

Gaier ED, Boudreault K, Rizzo JF, Falardeau J, Cestari DM. Atypical Optic Neuritis. Curr Neurol Neurosci Rep 2015;15(12):76.Abstract

Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features.

Lim LS, Ng WY, Wong D, Wong E, Yeo I, Ang CL, Kim L, Vavvas D, Lee SY. Prognostic factor analysis of vitrectomy for myopic foveoschisis. Br J Ophthalmol 2015;99(12):1639-43.Abstract

PURPOSE: To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement. METHODS: This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement. RESULTS: In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83±4.94D. Foveal detachment was present in 63.5% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84±0.59 logMAR units and the mean postoperative visual acuity was 0.64±0.64 logMAR units (mean difference 0.20±0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5%; p<0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6% vs 34.0%; p<0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95% CI 1.000 to 1.007), per μm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95% CI 0.2 to 1.72) poorer final acuity (p=0.02). CONCLUSIONS: Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors.

Miller JB, Yonekawa Y, Eliott D, Kim IK, Kim LA, Loewenstein JI, Sobrin L, Young LH, Mukai S, Vavvas DG. Long-term Follow-up and Outcomes in Traumatic Macular Holes. Am J Ophthalmol 2015;160(6):1255-1258.e1.Abstract

PURPOSE: To review presenting characteristics, clinical course, and long-term visual and anatomic outcomes of patients with traumatic macular holes at a tertiary referral center. DESIGN: Retrospective case series. METHODS: Twenty-eight consecutive patients with traumatic macular holes at a single tertiary referral center were reviewed. In addition to visual acuities and treatments throughout the clinical course, specific dimensions of the macular hole, including diameters, height, configuration, shape, and the presence of a cuff of fluid, were examined using spectral-domain optical coherence tomography (OCT). RESULTS: Twenty-eight patients were identified with a mean initial visual acuity (VA) of logMAR 1.3 (20/400) and a mean follow-up of 2.2 years. Eleven holes (39.3%) closed spontaneously in median 5.7 weeks. Eleven underwent vitrectomy with a median time to intervention of 35.1 weeks. Median time to surgery for the 5 eyes with successful hole closure was 11.0 weeks vs 56.3 weeks for the 6 eyes that failed to close (P = .02). VA improved in closed holes (P < .01), whether spontaneously (P < .01) or via vitrectomy (P = .04), but VA did not improve in holes that did not close (P = .22). There was no relation between initial OCT dimensions and final hole closure status, although there was a trend, which did not reach statistical significance, toward small dimensions for those that closed spontaneously. CONCLUSIONS: A fairly high spontaneous closure rate was observed, with a trend toward smaller OCT dimensions. We found no relationship between hole closure and the OCT characteristics of the hole. Surgical intervention was less successful at hole closure when elected after 3 months.

Modjtahedi BS, Fortenbach CR, Lorch AC. Optic Nerve Head Avulsion: Clinical, Radiographic, and Sonographic Correlations. Ophthalmology 2015;122(12):2442.
Odorcic S, Haas W, Gilmore MS, Dohlman CH. Fungal Infections After Boston Type 1 Keratoprosthesis Implantation: Literature Review and In Vitro Antifungal Activity of Hypochlorous Acid. Cornea 2015;34(12):1599-605.Abstract

PURPOSE: To review the current literature describing cases of fungal keratitis and endophthalmitis after Boston keratoprosthesis (KPro) implantation and to characterize the antifungal activity of 0.01% hypochlorous acid against medically relevant fungi. METHODS: A literature review of fungal keratitis or endophthalmitis in KPro patients from January 2001 to April 2015, and an in vitro time kill assay characterizing the fungicidal activity of 0.01% hypochlorous acid against fungi causing ocular infections. RESULTS: Fifteen publications, predominantly retrospective case series, were identified. Infection rates after KPro implantation ranged from 0.009 to 0.02 fungal infections per patient-year of follow-up. The largest single-surgeon series reported an incidence of 2.4% for fungal endophthalmitis during a 10-year period. Causative organisms included both yeasts and molds. Outcomes were favorable if infections were caught early and treated appropriately; less favorable outcomes were reported in developing countries where fungal species are endemic and resources are limited. 0.01% hypochlorous acid is rapidly fungicidal, reducing the number of viable yeast cells or mold conidia by at least 99.99% within 60 seconds. The antifungal activity extended to all molds (Acremonium kiliense, Aspergillus flavus, Aspergillus fumigatus, Fusarium solani, and Mucor indicus) and yeast species (Candida albicans and Candida parapsilosis) tested. CONCLUSIONS: Fungal infections remain a lifelong concern in patients after KPro implantation. There is a growing need for a standard antifungal prophylaxis regimen, especially in the developing world. The rapid broad-spectrum in vitro fungicidal activity of 0.01% hypochlorous acid against all fungi tested makes it an attractive candidate as an antifungal prophylaxis in KPro patients.


PURPOSE: To evaluate the efficacy of systemic infliximab for the induction of remission in patients with retinal vasculitis, inadequately responsive to other immunomodulatory therapy, based on fluorescein angiography grading for retinal vasculitis evaluation. METHODS: We analyzed 60 patients with retinal vasculitis, from the Massachusetts Eye Research and Surgery Institution in Cambridge, MA. Response to therapy was based on analysis of serial fluorescein angiography and fundus photography, including a baseline angiogram before initiation of infliximab. RESULTS: Sixty patients received infliximab therapy between July 2007 and July 2012 at Massachusetts Eye Research and Surgery Institution for a diagnosis of retinal vasculitis. All had previously showed a poor clinical response to other immunomodulatory regimens, or ceased therapy due to intolerable side effects. The initial dose of infliximab was 5 mg/kg in all patients and remained at this dose for the extent of treatment in 57 (95%) patients. At 6 months, 45 of 51 (88.23%) patients were maintaining remission with therapy, 5 (9.8%) were in partial remission, and 1 patient had failed. At 12 months, 39 of 39 (100%) patients were maintaining remission with therapy. CONCLUSION: Infliximab is effective for the treatment of recalcitrant noninfectious retinal vasculitis, refractory to conventional immunomodulatory therapy.

Silva PS, Dela Cruz AJ, Ledesma MG, van Hemert J, Radwan A, Cavallerano JD, Aiello LM, Sun JK, Aiello LP. Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography. Ophthalmology 2015;122(12):2465-72.Abstract

PURPOSE: To assess whether the presence of peripheral nonperfusion on ultrawide field (UWF) fluorescein angiography (FA) is associated with diabetic retinopathy (DR) severity and the presence of predominantly peripheral lesions (PPLs). DESIGN: Single-site, cross-sectional, retrospective study. PARTICIPANTS: Sixty-eight eyes of 37 diabetic subjects with or without DR and no history of prior panretinal laser photocoagulation. METHODS: Both 200° UWF images and UWF FA images were acquired at the same visit. Early Treatment Diabetic Retinopathy Study (ETDRS) templates were overlaid digitally based on disc and macula location onto stereographically projected UWF images. Images were evaluated for the presence of PPLs, defined as more than 50% of the graded lesion located outside the ETDRS field in each of the 5 extended fields. The UWF-FA images were evaluated by 2 masked, independent graders for extent of retinal nonperfusion area (NPA) and nonperfusion index (NPI; nonperfused/total gradable area). MAIN OUTCOME MEASURES: Association of NPA and NPI with DR severity and presence of PPLs. RESULTS: Distribution of DR severity was as follows: no DR, 8.8% eyes; mild nonproliferative DR (NPDR), 17.6%; moderate NPDR, 32.4%; severe NPDR, 17.6%; proliferative DR (PDR), 19.1%; and high-risk PDR, 4.4%; with PPL present in 61.8%. There was strong intragrader (r = 0.95) and intergrader (r = 0.86) agreement for NPA. Presence of PPLs was associated with increased NPA (191.8 mm(2) vs. 306.1 mm(2); P = 0.0019) and NPI (0.25 vs. 0.43; P = 0.0003). These relationships remained significant after adjusting for DR severity and diabetes duration. In eyes without PDR (n = 52), increasing NPA and NPI was associated with worsening DR (NPA, P = 0.001; NPI, P = 0.0003). NPA and NPI were not associated with clinically significant macular edema (NPA, P = 0.99; NPI, P = 0.67), nor correlated with visual acuity (NPA, r = 0.14, P = 0.23; NPI, r = 0.24, P = 0.05). CONCLUSIONS: Following a standardized protocol, the evaluation of UWF FA for NPA and NPI is reproducible. Both parameters are correlated highly with the presence of PPLs and DR severity. Given that the presence and extent of PPLs have been associated with increased risks of DR progression, the clinical identification of PPLs may reflect closely the extent of nonperfusion and ischemia, thus accounting for the increased risk of progression.

Stagner AM, Jakobiec FA, Iwamoto MA. Invasive Squamous Cell Carcinoma With Clear Cell Change of the Eyelid Arising in a Seborrheic Keratosis. JAMA Ophthalmol 2015;:1-2.
Thanos A, Esmaili DD, Eliott D. Cotton-Wool Spots Associated With Mild Nonprogressive Visual Loss. JAMA Ophthalmol 2015;:1-2.
White ML, Chodosh J, Jang J, Dohlman C. Incidence of Stevens-Johnson Syndrome and Chemical Burns to the Eye. Cornea 2015;34(12):1527-33.Abstract

PURPOSE: This population-based observational study was designed to estimate the incidence and distribution of SJS-spectrum (Stevens-Johnson syndrome, toxic epidermal necrolysis, and toxic epidermal Necrolysis/Stevens-Johnson syndrome overlap) and chemical burns (alkali or acid burn of the cornea/conjunctiva) in the United States and extrapolate these numbers to the world. METHODS: All patients evaluated in 961 hospital-based US emergency departments between July 1, 2010, and June 30, 2012 were identified retrospectively using the Nationwide Emergency Department Sample (NEDS) from the Agency for Healthcare Research and Quality. SJS-spectrum and chemical burn cases were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. RESULTS: A mean of 3834 new SJS-spectrum cases per year were identified in the United States, resulting in an incidence rate of 12.35 new cases per million per year. Similarly, a mean of 15,865 new chemical burn cases per year were identified, resulting in an incidence rate of 51.10 new cases per million per year. CONCLUSIONS: If the incidence of SJS-spectrum is approximately uniform the world-over, extrapolation from the US figure would amount to approximately 86,500 new cases per year in the world. Extrapolation of ocular chemical burns to the world is difficult because the incidence and severity are anticipated to be higher in the developing world than in the United States. Still, using a US incidence rate, a minimum of 357,710 burn accidents would be expected to occur worldwide every year; there are presently too few data available to calculate the degree of severity and bilaterality.

Wolfe JM, Boettcher SEP, Josephs EL, Cunningham CA, Drew T. You look familiar, but I don't care: Lure rejection in hybrid visual and memory search is not based on familiarity. J Exp Psychol Hum Percept Perform 2015;41(6):1576-87.Abstract

In "hybrid" search tasks, observers hold multiple possible targets in memory while searching for those targets among distractor items in visual displays. Wolfe (2012) found that, if the target set is held constant over a block of trials, reaction times (RTs) in such tasks were a linear function of the number of items in the visual display and a linear function of the log of the number of items held in memory. However, in such tasks, the targets can become far more familiar than the distractors. Does this "familiarity"- operationalized here as the frequency and recency with which an item has appeared-influence performance in hybrid tasks In Experiment 1, we compared searches where distractors appeared with the same frequency as the targets to searches where all distractors were novel. Distractor familiarity did not have any reliable effect on search. In Experiment 2, most distractors were novel but some critical distractors were as common as the targets while others were 4× more common. Familiar distractors did not produce false alarm errors, though they did slightly increase RTs. In Experiment 3, observers successfully searched for the new, unfamiliar item among distractors that, in many cases, had been seen only once before. We conclude that when the memory set is held constant for many trials, item familiarity alone does not cause observers to mistakenly confuse target with distractors. (PsycINFO Database Record

Wu J, Cho E, Willett WC, Sastry SM, Schaumberg DA. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up. JAMA Ophthalmol 2015;:1-10.Abstract

Importance: Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated. Objective: To investigate the associations between intakes of carotenoids and AMD. Design, Setting, and Participants: Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63 443 women and 38 603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline. Main Outcomes and Measures: Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined. Results: We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD. Conclusions and Relevance: Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

van Zyl T, Stagner AM, Jakobiec FA, Yoon MK. Histopathologic features of a resolving orbital Langerhans cell histiocytosis. Graefes Arch Clin Exp Ophthalmol 2015;253(12):2341-3.