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Wells JA, Glassman AR, Jampol LM, Aiello LP, Antoszyk AN, Baker CW, Bressler NM, Browning DJ, Connor CG, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW, Beck RW. Association of Baseline Visual Acuity and Retinal Thickness With 1-Year Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema. JAMA Ophthalmol 2015;:1-8.Abstract

Importance: Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment. Objective: To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography. Design, Setting, and Participants: Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015. Interventions: Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. Main Outcomes and Measures: One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST. Results: In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (-8% to 35%) for aflibercept vs ranibizumab. Conclusions and Relevance: These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients. Trial Registration: clinicaltrials.gov Identifier: NCT01627249.

Wen G, Aizenman A, Drew T, Wolfe JM, Haygood TM, Markey MK. Computational assessment of visual search strategies in volumetric medical images. J Med Imaging (Bellingham) 2016;3(1):015501.Abstract

When searching through volumetric images [e.g., computed tomography (CT)], radiologists appear to use two different search strategies: "drilling" (restrict eye movements to a small region of the image while quickly scrolling through slices), or "scanning" (search over large areas at a given depth before moving on to the next slice). To computationally identify the type of image information that is used in these two strategies, 23 naïve observers were instructed with either "drilling" or "scanning" when searching for target T's in 20 volumes of faux lung CTs. We computed saliency maps using both classical two-dimensional (2-D) saliency, and a three-dimensional (3-D) dynamic saliency that captures the characteristics of scrolling through slices. Comparing observers' gaze distributions with the saliency maps showed that search strategy alters the type of saliency that attracts fixations. Drillers' fixations aligned better with dynamic saliency and scanners with 2-D saliency. The computed saliency was greater for detected targets than for missed targets. Similar results were observed in data from 19 radiologists who searched five stacks of clinical chest CTs for lung nodules. Dynamic saliency may be superior to the 2-D saliency for detecting targets embedded in volumetric images, and thus "drilling" may be more efficient than "scanning."

Werdich XQ, Jakobiec FA, Curtin HD, Fay A. A clinical, radiologic, and immunopathologic study of five periorbital intraosseous cavernous vascular malformations. Am J Ophthalmol 2014;158(4):816-826.e1.Abstract

PURPOSE: To correlate the clinical, radiographic, histopathologic, and immunohistochemical features of 5 primary periorbital intraosseous cavernous vascular malformations. DESIGN: Retrospective interventional case series. METHODS: Clinical and operative records and radiographic images were reviewed. Histopathologic slides were evaluated with hematoxylin-eosin, trichrome, and elastin stains. Immunohistochemical studies were performed with a spectrum of monoclonal antibodies directed at antigens of vascular cells. RESULTS: Three men and 2 women ranged in age from 36 to 64 years. Vision was unaffected and there was no proptosis or globe displacement. The slow-growing lesions measured 13-25 mm in greatest diameter (mean 16.4 mm). Computed tomographic studies revealed that 2 lesions were situated in the maxillary bone, 2 in the frontal, and 1 in the zygoma, all anteriorly and with circumscribed, lucent, honeycombed, or sunburst characteristics. Histopathologically the lesions were composed of cavernous or telangiectatic channels; 1 showed advanced fibrotic vascular involution. Immunohistochemistry demonstrated CD31/34 positivity for vascular endothelium and D2-40 negativity for lymphatic endothelium. A typically thin mural myofibroblastic cuff was smooth muscle actin positive, weakly calponin positive, and desmin negative. Glucose transporter-1 and Ki-67 were negative in the endothelium. CONCLUSIONS: Intraosseous vascular lesions resemble orbital cavernous venous malformations (not true hemangiomas), except that their vascular walls are thinner owing to the constraints imposed by neighboring bone spicules, which limit the amount of interstitium from which mural myofibroblasts can be recruited. The bony trabeculae conferred the honeycomb or sunburst appearances observed radiographically. En bloc excision of these lesions was successful and avoided complications (mean follow-up, 46 months).

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.

Whitman MC, Andrews C, Chan W-M, Tischfield MA, Stasheff SF, Brancati F, Ortiz-Gonzalez X, Nuovo S, Garaci F, MacKinnon SE, Hunter DG, Grant EP, Engle EC. Two unique TUBB3 mutations cause both CFEOM3 and malformations of cortical development. Am J Med Genet A 2016;170(2):297-305.Abstract

One set of missense mutations in the neuron specific beta tubulin isotype 3 (TUBB3) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3-associated phenotypes, and implicate similar microtubule dysfunction underlying both. © 2015 Wiley Periodicals, Inc.

Whitman MC, MacNeill K, Hunter DG. Bifocals Fail to Improve Stereopsis Outcomes in High AC/A Accommodative Esotropia. Ophthalmology 2016;123(4):690-6.Abstract

PURPOSE: To assess whether stereopsis outcomes of patients with accommodative esotropia with high accommodative convergence/accommodation relationship (AC/A) were improved after treatment with bifocal glasses compared with single-vision lenses. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with high AC/A accommodative esotropia; evidence of stereopsis, binocularity (on Worth 4-dot testing), or improvement in near angle with +3.00 D lenses; and at least 4 years of records available for review, who were seen in the Department of Ophthalmology at Boston Children's Hospital between 2006 and 2014. METHODS: Use of bifocal or single-vision glasses. Charts were reviewed retrospectively. Stereopsis was log transformed for statistical analysis. Linear (for stereopsis) or logistic (for surgery) regression was used to control for confounders. MAIN OUTCOME MEASURES: Stereopsis at final follow-up, difference in stereopsis between final and initial visits, and progression to strabismus surgery. Secondary outcomes included final near and distance deviations. RESULTS: Of the 180 patients who met inclusion criteria, 77 used bifocals and 103 used single-vision lenses. Bifocals did not improve stereopsis outcomes compared with single-vision lenses. In both groups, stereopsis was similar at the initial and final visits, with similar improvement in both groups. Children in the bifocal group had a 3.6-fold higher rate of strabismus surgery than children in the single-lens group (P = 0.04.) Additionally, children in the bifocal group had near deviations 4 PD larger than those with single lenses at final follow-up, even after controlling for age and initial deviation (P = 0.02). These results did not change if surgical patients were eliminated or in the subgroup with initial distance deviation of 0 PD in full hyperopic correction. CONCLUSIONS: Despite their widespread use, there is no evidence that bifocals improve outcomes in children with accommodative esotropia with high AC/A. In our retrospective review, children with bifocals had higher surgical rates and a smaller improvement in near deviation over time. Although our results suggest that eliminating bifocals could reduce the cost and complexity of care while potentially improving quality, prospective, randomized controlled trials are needed to determine whether a change in practice is warranted.

Wiecek E, Dakin SC, Bex P. Metamorphopsia and letter recognition. J Vis 2014;14(14)Abstract

Acuity is the most commonly used measure of visual function, and reductions in acuity are associated with most eye diseases. Metamorphopsia-a perceived distortion of visual space-is another common symptom of visual impairment and is currently assessed qualitatively using Amsler (1953) charts. In order to quantify the impact of metamorphopsia on acuity, we measured the effect of physical spatial distortion on letter recognition. Following earlier work showing that letter recognition is tuned to specific spatial frequency (SF) channels, we hypothesized that the effect of distortion might depend on the spatial scale of visual distortion just as it depends on the spatial scale of masking noise. Six normally sighted observers completed a 26 alternate forced choice (AFC) Sloan letter identification task at five different viewing distances, and the letters underwent different levels of spatial distortion. Distortion was controlled using spatially band-pass filtered noise that spatially remapped pixel locations. Noise was varied over five spatial frequencies and five magnitudes. Performance was modeled with logistic regression and worsened linearly with increasing distortion magnitude and decreasing letter size. We found that retinal SF affects distortion at midrange frequencies and can be explained with the tuning of a basic contrast sensitivity function, while object-centered distortion SF follows a similar pattern of letter object recognition sensitivity and is tuned to approximately three cycles per letter (CPL). The interaction between letter size and distortion makes acuity an unreliable outcome for metamorphopsia assessment.

Wiecek E, Lashkari K, Dakin SC, Bex P. A statistical analysis of metamorphopsia in 7106 amsler grids. Ophthalmology 2015;122(2):431-3.
Wiecek E, Lashkari K, Dakin S, Bex PJ. Novel Quantitative Assessment of Metamorphopsia in Maculopathy. Invest Ophthalmol Vis Sci 2014;Abstract

Purpose: Patients with macular disease often report experiencing metamorphopsia (visual distortion). Although typically measured with Amsler charts, more objective and quantitative assessments of perceived distortion are desirable to effectively monitor the presence, progression and remediation of visual impairment. Methods: Participants with binocular (n = 33) and monocular (n= 50) maculopathy across seven disease groups, and control participants (n = 10) with no identifiable retinal disease completed a modified Amsler Grid assessment (presented on a computer screen with eye tracking to ensure fixation compliance) and two novel objective measures of metamorphopsia in the central five degrees of visual field. 81% (67/83) of participants completed a task requiring them to configure eight dots in the shape of a square, and 64% (32/50) of participants experiencing monocular distortion completed a spatial alignment task using dichoptic stimuli. 10 controls completed all tasks. Results: Horizontal and vertical distortion magnitudes were calculated for each of the three assessments. Distortion magnitudes were significantly higher in patients than controls in all assessments. There was no significant difference in magnitude of distortion across different macular diseases. Among patients, there were no significant correlations between overall magnitude of distortion among any of the three measures and no significant correlations in localized measures of distortion. Conclusions: Three alternative quantifications of monocular spatial distortion in the central visual field generated uncorrelated estimates of visual distortion. It is therefore unlikely that metamorphopsia is caused solely by displacement of photoreceptors in the retina, but instead involves additional top-down information, knowledge about the scene, and perhaps, cortical reorganization.

Wiecek E, Lashkari K, Dakin SC, Bex P. Metamorphopsia and interocular suppression in monocular and binocular maculopathy. Acta Ophthalmol 2015;93(4):e318-20.
Wiggs JL, Pasquale LR. Expression and Regulation of LOXL1 and Elastin-related Genes in Eyes With Exfoliation Syndrome. J Glaucoma 2014;:S62-3.Abstract

Variants in LOXL1 are significantly associated with exfoliation syndrome (XFS), however the impact of the associated variants on disease development is not yet understood. Initially the associated missense changes, R141L and G153D, were considered to be pathogenic alleles. Flipping of the risk allele in certain populations for both missense variants provided strong evidence that these missense changes are not biologically significant and suggest that other LOXL1 variant(s), in linkage disequilibrium with these missense variants, predispose to exfoliation syndrome by affecting gene expression or protein function. Several lines of evidence support dysregulation of LOXL1 gene expression as a contributing factor to disease development. First, in the German population the R141L (rs1048661) risk allele reduced LOXL1 expression by 20%. Second, haplotype analysis identified a risk haplotype that includes including R141L, G153D, as well as a LOXL1 promoter region variant previously shown to reduce gene expression (rs16958477). Third, the LOXL1 risk haplotype influences gene expression induced by disease-associated factors TGF-B1, oxidative stress, UV light and hypoxia. Finally, a LOXL1 null mouse has some features of XFS suggesting that decreased enzyme activity contributes to predisposition to the disease. Collectively, these results suggest that dysregulation of LOXL1 expression is a contributing factor to exfoliation disease development.

Wiggs JL, Pasquale LR. Genetics of Glaucoma. Hum Mol Genet 2017;Abstract
Genetic and genomic studies, including genome-wide association studies (GWAS) have accelerated the discovery of genes contributing to glaucoma, the leading cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with Mendelian inheritance typical for rare early onset disease (before age 40) and complex inheritance evident in common adult-onset forms of disease. Recent studies have suggested possible therapeutic targets for some patients with early-onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN and TBK1 mutations. Diagnostic genetic tests using early-onset glaucoma genes are also proving useful for pre-symptomatic disease detection and genetic counseling. Recent GWAS completed for three types of common adult-onset glaucoma have identified novel loci for POAG (primary-open-angle glaucoma) (ABCA1, AFAP1, GMDS, PMM2, TGFBR3, FNDC3B, ARHGEF12, GAS7, FOXC1, ATXN2, TXNRD2); PACG (primary angle-closure glaucoma (EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102); and exfoliation syndrome (XFS) glaucoma (CACNA1A). In total sixteen genomic regions have been associated with POAG (including the normal tension glaucoma (NTG) subgroup), 8 with PACG and 2 with XFS. These studies are defining important biological pathways and processes that contribute to disease pathogenesis.
Wilsey L, Gowrisankaran S, Cull G, Hardin C, Burgoyne CF, Fortune B. Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure. Doc Ophthalmol 2017;134(2):111-128.Abstract

PURPOSE: To compare diagnostic performance and structure-function correlations of multifocal electroretinogram (mfERG), full-field flash ERG (ff-ERG) photopic negative response (PhNR) and transient pattern-reversal ERG (PERG) in a non-human primate (NHP) model of experimental glaucoma (EG). METHODS: At baseline and after induction of chronic unilateral IOP elevation, 43 NHP had alternating weekly recordings of retinal nerve fiber layer thickness (RNFLT) by spectral domain OCT (Spectralis) and retinal function by mfERG (7F slow-sequence stimulus, VERIS), ff-ERG (red 0.42 log cd-s/m(2) flashes on blue 30 scotopic cd/m(2) background, LKC UTAS-E3000), and PERG (0.8° checks, 99% contrast, 100 cd/m(2) mean, 5 reversals/s, VERIS). All NHP were followed at least until HRT-confirmed optic nerve head posterior deformation, most to later stages. mfERG responses were filtered into low- and high-frequency components (LFC, HFC, >75 Hz). Peak-to-trough amplitudes of LFC features (N1, P1, N2) and HFC RMS amplitudes were measured and ratios calculated for HFC:P1 and N2:P1. ff-ERG parameters included A-wave (at 10 ms), B-wave (trough-to-peak) and PhNR (baseline-to-trough) amplitudes as well as PhNR:B-wave ratio. PERG parameters included P50 and N95 amplitudes as well as N95:P50 ratio and N95 slope. Diagnostic performance of retinal function parameters was compared using the area under the receiver operating characteristic curve (A-ROC) to discriminate between EG and control eyes. Correlations to RNFLT were compared using Steiger's test. RESULTS: Study duration was 15 ± 8 months. At final follow-up, structural damage in EG eyes measured by RNFLT ranged from 9% above baseline (BL) to 58% below BL; 29/43 EG eyes (67%) and 0/43 of the fellow control eyes exhibited significant (>7%) loss of RNFLT from BL. Using raw parameter values, the largest A-ROC findings for mfERG were: HFC (0.82) and HFC:P1 (0.90); for ff-ERG: PhNR (0.90) and PhNR:B-wave (0.88) and for PERG: P50 (0.64) and N95 (0.61). A-ROC increased when data were expressed as % change from BL, but the pattern of results persisted. At 95% specificity, the diagnostic sensitivity of mfERG HFC:P1 ratio was best, followed by PhNR and PERG. The correlation to RNFLT was stronger for mfERG HFC (R = 0.65) than for PhNR (R = 0.59) or PERG N95 (R = 0.36), (p = 0.20, p = 0.0006, respectively). The PhNR flagged a few EG eyes at the final time point that had not been flagged by mfERG HFC or PERG. CONCLUSIONS: Diagnostic performance and structure-function correlation were strongest for mfERG HFC as compared with ff-ERG PhNR or PERG in NHP EG.

Wilson ME, O'Halloran H, VanderVeen D, Roarty J, Plager DA, Markwardt K, Gedif K, Lambert SR. Difluprednate versus prednisolone acetate for inflammation following cataract surgery in pediatric patients: a randomized safety and efficacy study. Eye (Lond) 2016;30(9):1187-94.Abstract

PurposeTo evaluate safety and efficacy of difluprednate 0.05% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05% four times daily or prednisolone acetate 1% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5%, n=1; prednisolone acetate 1%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05% compared with prednisolone acetate 1%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05%, n=30 (78.9%); prednisolone acetate 1%, n=31 (77.5%). Compared with prednisolone acetate 1%, approximately twice as many difluprednate 0.05%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8%) vs n=7 (17.5%) and day 8 (n=18 (48.7%) vs n=10 (25.0%).ConclusionsDifluprednate 0.05% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1% four times daily in children 0-3 years undergoing cataract surgery.

Wirostko B, Rafii MJ, Sullivan DA, Morelli J, Ding J. Novel Therapy to Treat Corneal Epithelial Defects: A Hypothesis with Growth Hormone. Ocul Surf 2015;13(3):204-212.e1.Abstract

Impaired corneal wound healing that occurs with ocular surface disease, trauma, systemic disease, or surgical intervention can lead to persistent corneal epithelial defects (PCED), which result in corneal scarring, ulceration, opacification, corneal neovascularization, and, ultimately, visual compromise and vision loss. The current standard of care can include lubricants, ointments, bandage lenses, amniotic membranes, autologous serum eye drops, and corneal transplants. Various inherent problems exist with application and administration of these treatments, which often may not result in a completely healed surface. A topically applicable compound capable of promoting corneal epithelial cell proliferation and/or migration would be ideal to accelerate healing. We hypothesize that human growth hormone (HGH) is such a compound. In a recent study, HGH was shown to activate signal transducer and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial migration in a co-culture system of corneal epithelial cells and fibroblasts. These effects require an intact communication between corneal epithelia and fibroblasts. Further, HGH promotes corneal wound healing in a rabbit debridement model, thus demonstrating the effectiveness of HGH in vivo as well. In conclusion, HGH may represent an exciting and effective topical therapeutic to promote corneal wound healing.

Witkin AJ, Shah AR, Engstrom RE, Kron-Gray MM, Baumal CR, Johnson MW, Witkin DI, Leung J, Albini TA, Moshfeghi AA, Batlle IR, Sobrin L, Eliott D. Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin. Ophthalmology 2015;122(7):1438-51.Abstract

PURPOSE: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN: Retrospective case series. SUBJECTS: Eleven eyes of 6 patients from 6 different institutions. METHODS: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

Witkin AJ, Chang DF, Jumper MJ, Charles S, Eliott D, Hoffman RS, Mamalis N, Miller KM, Wykoff CC. Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes. Ophthalmology 2017;124(5):583-595.Abstract

PURPOSE: To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-six eyes of 23 patients. METHODS: The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies' web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases. MAIN OUTCOME MEASURES: Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes. RESULTS: Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61%) had 20/200 or worse visual acuity and 8 of 36 eyes (22%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements. CONCLUSIONS: Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.

Wladis EJ, Shinder R, Lefebvre DR, Sokol JA, Boyce M. Clinical and microbiologic features of dacryocystitis-related orbital cellulitis. Orbit 2016;35(5):258-61.Abstract

Dacryocystitis-related orbital cellulitis is a relatively rare condition, and large case series of this clinical entity have been reported. This study was undertaken to identify a larger cohort of patients with this ailment, with the intent of defining its clinical and microbiologic features. Case logs from four institutions were reviewed to identify patients that suffered from dacryocystitis-related orbital cellulitis. A retrospective chart review was then performed to identify clinical features, management strategies, microbiologic features, and outcomes. A dedicated statistical software package was utilized to identify correlations between these variables. 13 patients (7 females, 6 males; mean age = 57.2 years, range = 7-89 years) were identified. One patient carried a diagnosis of immunosuppressive disease. All patients underwent emergent surgical drainage and received intravenous antibiotics. Primary acquired nasolacrimal duct obstruction was found to be the underlying etiology in nine cases (69.2%), whereas four patients suffered from specific causes of their obstructions. An average of 1.07 organisms/patient (standard deviation = 0.49 organisms/patient) were recovered from microbiologic cultures, and Gram-positive bacteria represented the majority of cultured organisms. All patients experienced either stable or improved vision upon discharge. The relationships between a specific etiology and the possibility of vision loss or the number of organisms cultured, between the number of organisms cultured and vision loss, and immunosuppression and vision loss or the number of organisms cultured were all not statistically significant (p > 0.05). Dacryocystitis-related orbital cellulitis most commonly occurs in adult patients who do not carry immunosuppressive diagnoses and suffer from primary obstructions. Multiple microbiologic species may cause this problem, although Gram-positive organisms are most common. With appropriate management, stable or improved vision can be achieved.

Wolfe JM, Evans KK, Drew T, Aizenman A, Josephs E. HOW DO RADIOLOGISTS USE THE HUMAN SEARCH ENGINE?. Radiat Prot Dosimetry 2016;169(1-4):24-31.Abstract

Radiologists perform many 'visual search tasks' in which they look for one or more instances of one or more types of target item in a medical image (e.g. cancer screening). To understand and improve how radiologists do such tasks, it must be understood how the human 'search engine' works. This article briefly reviews some of the relevant work into this aspect of medical image perception. Questions include how attention and the eyes are guided in radiologic search? How is global (image-wide) information used in search? How might properties of human vision and human cognition lead to errors in radiologic search?

Wolfe JM, Aizenman AM, Boettcher SEP, Cain MS. Hybrid foraging search: Searching for multiple instances of multiple types of target. Vision Res 2016;119:50-9.Abstract

This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search.

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