2014

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Aggarwal S, Cavalcanti BM, Pavan-Langston D. Treatment of pseudodendrites in herpes zoster ophthalmicus with topical ganciclovir 0.15% gel. Cornea 2014;33(2):109-13.Abstract
PURPOSE: There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15% ganciclovir for treatment of these lesions. METHODS: This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite being given oral antiviral treatment and who underwent 0.15% ganciclovir gel topical treatment. Main outcome measures included epithelial healing time, visual acuity, and corneal sensation. RESULTS: All 4 patients were immunocompetent and had epithelial lesions unresponsive to antiviral treatment with oral valacyclovir. Treatment with topical 0.15% ganciclovir gel 5 times a day resulted in the lesions healing successfully within 7 days with improved visual acuity in 3 patients and an increase in corneal sensation in 2 of the 4 patients. CONCLUSIONS: Topical 0.15% ganciclovir gel, 5 times a day until pseudodendritic lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective treatment for pseudodendrites in HZO-affected cases that are often a challenge to manage with other oral or topical antivirals.
Aggarwal S, Jakobiec FA, Hamrah P. Bilateral adult epibulbar xanthogranulomas suspicious for Erdheim-Chester disease. Cornea 2014;33(10):1113-7.Abstract

PURPOSE: The aim of this study was to report the clinical, imaging, and histopathological findings of bilateral, conjunctival adult-onset xanthogranulomas that raised the prospect of a mild form of Erdheim-Chester disease. METHODS: This is a case report. RESULTS: A 35-year-old white male complaining of ocular irritation, presented with bilateral, nasal and temporal, yellow, elevated conjunctival lumps first noticed 1.5 years back, which were not associated with other ocular findings. The lesions were firm, attached to the underlying episclera, and measured 1.1 × 0.9, 1.1 × 0.8, 1.2 × 0.5, and 0.5 × 0.5 cm in the temporal and nasal right and left eyes, respectively. Each mass was fleshy with vascularity at the peripheral margin. Histopathologic evaluation after excisional biopsy revealed lipidized xanthoma cells, multiple Touton giant cells, and lymphocytes. Immunohistochemical staining was positive for adipophilin (lipid), CD68, CD163 histiocytes, CD3 T cells (with CD8 cytotoxic T cells > CD4 T-helper cells), and virtually no CD20 B cells or IgG4 plasma cells. The patient later acquired similar xanthogranulomatous subcutaneous lesions on the extremities. Positron emission tomography scans showed sclerosis in the medullary cavities of the tibia and the radius of both legs and arms, and an absence of retroperitoneal lesions. A normal serum immunoelectrophoresis and the absence of a BRAF gene mutation were demonstrated. CONCLUSIONS: Adult-onset xanthogranuloma can present as a solitary conjunctival mass without periocular or orbital involvement. The clinical, histopathologic, and radiologic findings in this case are suggestive of Erdheim-Chester disease without displaying any life-threatening lesions to date. Histopathologic and imaging studies can help in obtaining a diagnosis. Ophthalmologists should be aware that xanthogranulomatous conditions may have potential systemic implications, and a thorough systemic evaluation is recommended for lesions that initially seemed to be isolated in nature.

AL P, IS F, JM P, S M, JM S, M V, SP P, T L, SV K. Localization of sleep spindles, k-complexes, and vertex waves with subdural electrodes in children. J Clin Neurophysiol 2014;31(4):367-74.
Al-Moujahed A, Nicolaou F, Brodowska K, Papakostas TD, Marmalidou A, Ksander BR, Miller JW, Gragoudas E, Vavvas DG. Uveal melanoma cell growth is inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase. Invest Ophthalmol Vis Sci 2014;55(7):4175-85.Abstract
PURPOSE: To evaluate the effects and mechanism of aminoimidazole carboxamide ribonucleotide (AICAR), an AMP-dependent kinase (AMPK) activator, on the growth of uveal melanoma cell lines. METHODS: Four different cell lines were treated with AICAR (1-4 mM). Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Cell cycle analysis was conducted by flow cytometry; additionally, expression of cell-cycle control proteins, cell growth transcription factors, and downstream effectors of AMPK were determined by RT-PCR and Western blot. RESULTS: Aminoimidazole carboxamide ribonucleotide inhibited cell growth, induced S-phase arrest, and led to AMPK activation. Aminoimidazole carboxamide ribonucleotide treatment was associated with inhibition of eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker of mammalian target of rapamycin (mTOR) pathway activity. Aminoimidazole carboxamide ribonucleotide treatment was also associated with downregulation of cyclins A and D, but had minimal effects on the phosphorylation of ribosomal protein S6 or levels of the macroautophagy marker LC3B. The effects of AICAR were abolished by treatment with dipyridamole, an adenosine transporter inhibitor that blocks the entry of AICAR into cells. Treatment with adenosine kinase inhibitor 5-iodotubericidin, which inhibits the conversion of AICAR to its 5'-phosphorylated ribotide 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5'-monophosphate (ZMP; the direct activator of AMPK), reversed most of the growth-inhibitory effects, indicating that some of AICAR's antiproliferative effects are mediated at least partially through AMPK activation. CONCLUSIONS: Aminoimidazole carboxamide ribonucleotide inhibited uveal melanoma cell proliferation partially through activation of the AMPK pathway and downregulation of cyclins A1 and D1.
Alasil T, Wang K, Yu F, Field MG, Lee H, Baniasadi N, de Boer JF, Coleman AL, Chen TC. Correlation of retinal nerve fiber layer thickness and visual fields in glaucoma: a broken stick model. Am J Ophthalmol 2014;157(5):953-59.Abstract
PURPOSE: To determine the retinal nerve fiber layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. DESIGN: Retrospective cross-sectional study. METHODS: Eighty-seven healthy and 108 glaucoma subjects (1 eye per subject) were recruited from an academic institution. All patients had VF examinations (Swedish Interactive Threshold Algorithm 24-2 test of the Humphrey Visual Field Analyzer 750i) and spectral-domain optical coherence tomography RNFL scans. Comparison of RNFL thickness values with VF threshold values showed a plateau of VF threshold values at high RNFL thickness values and then a sharp decrease at lower RNFL thickness values. A broken stick statistical analysis was used to estimate the tipping point at which RNFL thickness values are associated with VF defects. The slope for the association between structure and function was computed for data above and below the tipping point. RESULTS: The mean RNFL thickness value that was associated with initial VF loss was 89 μm. The superior RNFL thickness value that was associated with initial corresponding inferior VF loss was 100 μm. The inferior RNFL thickness value that was associated with initial corresponding superior VF loss was 73 μm. The differences between all the slopes above and below the aforementioned tipping points were statistically significant (P < .001). CONCLUSIONS: In open-angle glaucoma, substantial RNFL thinning or structural loss appears to be necessary before functional visual field defects become detectable.
Alberti CF, Peli E, Bowers AR. Driving with hemianopia: III. Detection of stationary and approaching pedestrians in a simulator. Invest Ophthalmol Vis Sci 2014;55(1):368-74.Abstract
PURPOSE: To compare blind-side detection performance of drivers with homonymous hemianopia (HH) for stationary and approaching pedestrians, initially appearing at small (4°) or large (14°) eccentricities in a driving simulator. While the stationary pedestrians did not represent an imminent threat, as their eccentricity increased rapidly as the vehicle advanced, the approaching pedestrians maintained a collision course with approximately constant eccentricity, walking or running, toward the travel lane as if to cross. METHODS: Twelve participants with complete HH and without spatial neglect pressed the horn whenever they detected a pedestrian while driving along predetermined routes in two driving simulator sessions. Miss rates and reaction times were analyzed for 52 stationary and 52 approaching pedestrians. RESULTS: Miss rates were higher and reaction times longer on the blind than the seeing side (P < 0.01). On the blind side, miss rates were lower for approaching than stationary pedestrians (16% vs. 29%, P = 0.01), especially at larger eccentricities (20% vs. 54%, P = 0.005), but reaction times for approaching pedestrians were longer (1.72 vs. 1.41 seconds; P = 0.03). Overall, the proportion of potential blind-side collisions (missed and late responses) was not different for the two paradigms (41% vs. 35%, P = 0.48), and significantly higher than for the seeing side (3%, P = 0.002). CONCLUSIONS: In a realistic pedestrian detection task, drivers with HH exhibited significant blind-side detection deficits. Even when approaching pedestrians were detected, responses were often too late to avoid a potential collision.
Alberti CF, Horowitz T, Bronstad MP, Bowers AR. Visual attention measures predict pedestrian detection in central field loss: a pilot study. PLoS One 2014;9(2):e89381.Abstract
PURPOSE: The ability of visually impaired people to deploy attention effectively to maximize use of their residual vision in dynamic situations is fundamental to safe mobility. We conducted a pilot study to evaluate whether tests of dynamic attention (multiple object tracking; MOT) and static attention (Useful Field of View; UFOV) were predictive of the ability of people with central field loss (CFL) to detect pedestrian hazards in simulated driving. METHODS: 11 people with bilateral CFL (visual acuity 20/30-20/200) and 11 age-similar normally-sighted drivers participated. Dynamic and static attention were evaluated with brief, computer-based MOT and UFOV tasks, respectively. Dependent variables were the log speed threshold for 60% correct identification of targets (MOT) and the increase in the presentation duration for 75% correct identification of a central target when a concurrent peripheral task was added (UFOV divided and selective attention subtests). Participants drove in a simulator and pressed the horn whenever they detected pedestrians that walked or ran toward the road. The dependent variable was the proportion of timely reactions (could have stopped in time to avoid a collision). RESULTS: UFOV and MOT performance of CFL participants was poorer than that of controls, and the proportion of timely reactions was also lower (worse) (84% and 97%, respectively; p = 0.001). For CFL participants, higher proportions of timely reactions correlated significantly with higher (better) MOT speed thresholds (r = 0.73, p = 0.01), with better performance on the UFOV divided and selective attention subtests (r = -0.66 and -0.62, respectively, p<0.04), with better contrast sensitivity scores (r = 0.54, p = 0.08) and smaller scotomas (r = -0.60, p = 0.05). CONCLUSIONS: Our results suggest that brief laboratory-based tests of visual attention may provide useful measures of functional visual ability of individuals with CFL relevant to more complex mobility tasks.
Allmendinger AM, M Mallery R, Magro CM, Wang N, Egan RA, Samuels MA, Callahan A, Viswanadhan N, Klufas RA, Hsu L, Prasad S. Cauda equina involvement in Susac's syndrome. J Neurol Sci 2014;337(1-2):91-6.Abstract
Susac's syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susac's syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susac's syndrome. This case is important not only because it expands the clinical features of Susac's syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.
Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R. What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease?. Am J Ophthalmol 2014;157(1):69-77.e2.Abstract
PURPOSE: To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED). DESIGN: Retrospective, clinic-based cohort study. METHODS: In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits. Main outcomes included the correlation of the changes between the 2 visits for tear osmolarity (TearLab system), symptoms (Ocular Surface Disease Index), and corneal fluorescein staining (modified Oxford scheme). For tear osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients' treatment. RESULTS: We found a modest, though statistically significant, correlation between changes in corneal fluorescein staining and symptoms of DED (R = 0.31; P < .001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = -0.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = -0.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, whereas tear osmolarity changes did not. CONCLUSIONS: Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease.
Andreoli MT, Yiu G, Hart L, Andreoli CM. B-scan ultrasonography following open globe repair. Eye (Lond) 2014;28(4):381-5.Abstract
PURPOSE: To examine the accuracy and predictive ability of B-scan ultrasonography in the post-repair assessment of an open globe injury. METHODS: In all, 965 open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1 January 2000 and 1 June 2010 were retrospectively reviewed. A total of 427 ultrasound reports on 210 patients were analyzed. Ultrasound reports were examined for the following characteristics: vitreous hemorrhage, vitreous tag, retinal tear, RD (including subcategories total RD, partial RD, closed funnel RD, open funnel RD, and chronic RD), vitreous traction, vitreous debris, serous choroidal detachment, hemorrhagic choroidal detachment, kissing choroidal detachment, dislocated crystalline lens, dislocated intraocular lens (IOL), disrupted crystalline lens, intraocular foreign body (IOFB), intraocular air, irregular posterior globe contour, disorganized posterior intraocular contents, posterior vitreous detachment, choroidal vs retinal detachment, vitreal membranes, and choroidal thickening. The main outcome measure was visual outcome at final follow-up. RESULTS: Among 427 B-scan reports, there were a total of 57 retinal detachments, 19 retinal tears, 18 vitreous traction, 59 serous choroidal detachments, 47 hemorrhagic choroidal detachments, and 10 kissing choroidal detachments. Of patients with multiple studies, 26% developed retinal detachments or retinal tears on subsequent scans. Ultrasound had 100% positive predictive value for diagnosing retinal detachment and IOFB. The diagnoses of retinal detachment, disorganized posterior contents, hemorrhagic choroidal detachment, kissing choroidal detachment, and irregular posterior contour were associated with worse visual acuity at final follow-up. Disorganized posterior contents correlated with particularly poor outcomes. CONCLUSIONS: B-scan ultrasonography is a proven, cost-effective imaging modality in the management of an open globe injury. This tool can offer both diagnostic and prognostic information, useful for both surgical planning and further medical management.
Arafat SN, Robert M-C, Shukla AN, Dohlman CH, Chodosh J, Ciolino JB. UV cross-linking of donor corneas confers resistance to keratolysis. Cornea 2014;33(9):955-9.Abstract

PURPOSE: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. METHODS: Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1% riboflavin/20% dextran), and irradiated with ultraviolet A (UV-A) light (λ = 370 nm, irradiance = 3 mW/cm) for various durations. The combined effect of UV-A and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37°C with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. RESULTS: Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 ± 2.6 hours (P < 0.0001). The corneal tissues' resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P > 0.05). γ-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (P = 0.43). CONCLUSIONS: Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A.

Arboleda-Velasquez JF, Primo V, Graham M, James A, Manent J, D'Amore PA. Notch signaling functions in retinal pericyte survival. Invest Ophthalmol Vis Sci 2014;55(8):5191-9.Abstract
PURPOSE: Pericytes, the vascular cells that constitute the outer layer of capillaries, have been shown to have a crucial role in vascular development and stability. Loss of pericytes precedes endothelial cell dysfunction and vascular degeneration in small-vessel diseases, including diabetic retinopathy. Despite their clinical relevance, the cellular pathways controlling survival of retinal pericytes remain largely uncharacterized. Therefore, we investigated the role of Notch signaling, a master regulator of cell fate decisions, in retinal pericyte survival. METHODS: A coculture system of ligand-dependent Notch signaling was developed using primary cultured retinal pericytes and a mesenchymal cell line derived from an inducible mouse model expressing the Delta-like 1 Notch ligand. This model was used to examine the effect of Notch activity on pericyte survival using quantitative PCR (qPCR) and a light-induced cell death assay. The effect of Notch gain- and loss-of-function was analyzed in monocultures of retinal pericytes using antibody arrays to interrogate the expression of apoptosis-related proteins. RESULTS: Primary cultured retinal pericytes differentially expressed key molecules of the Notch pathway and displayed strong expression of canonical Notch/RBPJK (recombination signal-binding protein 1 for J-kappa) downstream targets. A gene expression screen using gain- and loss-of-function approaches identified genes relevant to cell survival as downstream targets of Notch activity in retinal pericytes. Ligand-mediated Notch activity protected retinal pericytes from light-induced cell death. CONCLUSIONS: Our results have identified signature genes downstream of Notch activity in retinal pericytes and suggest that tight regulation of Notch signaling is crucial for pericyte survival.
Arnoldner MA, Kheirkhah A, Jakobiec FA, Durand ML, Hamrah P. Successful treatment of Paecilomyces lilacinus keratitis with oral posaconazole. Cornea 2014;33(7):747-9.Abstract
PURPOSE: To report a case of successful medical treatment with oral posaconazole in refractory fungal keratitis caused by Paecilomyces lilacinus. METHODS: Case report. RESULTS: A 57-year-old male, soft contact lens wearer presented with irritation, pain, photophobia, and reduced vision. Slit-lamp examination showed a large corneal epithelial defect with a peripheral infiltrate. The patient did not improve on fortified topical antibiotics. After the diagnosis of P. lilacinus fungal keratitis, oral voriconazole and topical antifungal therapy were started. Despite antifungal therapy, progressive disease required therapeutic penetrating keratoplasty. Postoperatively, because of clinical signs of recurrence and in vivo confocal microscopy findings of presumed hyphae in the cornea, intracameral miconazole was injected and oral posaconazole was started. The patient improved and demonstrated no hyphae 6 weeks after starting posaconazole. When posaconazole was stopped, the cornea remained clear with excellent acuity. However, because of acute graft rejection 2 months after stopping posaconazole, keratoprosthesis was implanted, with no evidence of infection at surgery or during the 3.5-year follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report on the use of oral posaconazole for Paecilomyces keratitis. Posaconazole might be indicated in the treatment of refractory Paecilomyces keratitis that is resistant to conventional therapy.
Artornsombudh P, Pistilli M, Foster SC, Pujari SS, Gangaputra SS, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Kempen JH. Factors predictive of remission of new-onset anterior uveitis. Ophthalmology 2014;121(3):778-84.Abstract
PURPOSE: To identify factors predictive of remission of inflammation in new-onset anterior uveitis cases treated at tertiary uveitis care facilities. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients seeking treatment at participating academic uveitis clinics within 90 days of initial diagnosis of anterior uveitis. METHODS: Retrospective cohort study based on standardized chart review. MAIN OUTCOME MEASURES: Factors predictive of remission (no disease activity without corticosteroid or immunosuppressive treatments at all visits during a 90-day period). RESULTS: Nine hundred ninety eyes (687 patients) had a first-ever diagnosis of anterior uveitis within 90 days before initial presentation and had follow-up visits thereafter. The median follow-up time was 160 days. Systemic diagnoses with juvenile idiopathic arthritis (JIA; adjusted hazard ratio [aHR], 0.38; 95% confidence interval [CI], 0.19-0.74) and Behçet's disease (aHR, 0.10; 95% CI, 0.01-0.85) were associated with a lower incidence of uveitis remission. Cases of bilateral uveitis (aHR, 0.68; 95% CI, 0.54-0.87) and those with a history of cataract surgery before presentation (aHR, 0.51; 95% CI, 0.29-0.87) also had a lower incidence of remission. Regarding clinical findings at the initial visit, a high degree of vitreous cells at initial presentation was associated with a lower incidence of remission (for 1+ or more vs. none: aHR, 0.72; 95% CI, 0.55-0.95). An initial visual acuity of 20/200 or worse, with respect to 20/40 or better, also was predictive of a lower incidence of remission (aHR, 0.52; 95% CI, 0.32-0.86). CONCLUSIONS: Factors associated with a lower incidence of remission among new-onset anterior uveitis cases included diagnosis with JIA, Behçet's disease, bilateral uveitis, history of cataract surgery, findings of 1+ or more vitreous cells at presentation, and an initial visual acuity of 20/200 or worse. Patients with these risk factors seem to be at higher risk of persistent inflammation; reciprocally, patients lacking these factors would be more likely to experience remission. Patients with risk factors for nonremission of uveitis should be managed taking into account the higher probability of a chronic inflammatory course.
Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. Author reply: To PMID 23972322. Ophthalmology 2014;121(8):e39.
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Bansal AK, Madhavan R, Agam Y, Golby A, Madsen JR, Kreiman G. Neural dynamics underlying target detection in the human brain. J Neurosci 2014;34(8):3042-55.Abstract
Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses.
Bauer CM, Heidary G, Koo B-B, Killiany RJ, Bex P, Merabet LB. Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment. J AAPOS 2014;18(4):398-401.Abstract
Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients.
Behlau I, Martin KV, Martin JN, Naumova EN, Cadorette JJ, Sforza TJ, Pineda R, Dohlman CH. Infectious endophthalmitis in Boston keratoprosthesis: incidence and prevention. Acta Ophthalmol 2014;92(7):e546-55.Abstract
PURPOSE: To determine the cumulative worldwide incidence of infectious endophthalmitis and associated vision loss after Boston keratoprosthesis (B-KPro) Type I/II implantation and to propose both safe and inexpensive prophylactic antibiotic regimens. METHODS: Two retrospective methods were used to determine the incidence, visual outcomes and aetiologies of infectious endophthalmitis associated with the B-KPro divided per decade: (i) systematic review of the literature from 1990 through January 2013 and (ii) a surveillance survey sent to all surgeons who implanted B-KPros through 2010 with 1-year minimum follow-up. In addition, a single-Boston surgeon 20-year experience was examined. RESULTS: From 1990 through 2010, there were 4729 B-KPros implanted worldwide by 209 U.S. surgeons and 159 international surgeons. The endophthalmitis cumulative mean incidence declined from 12% during its first decade of use to about 3% during its second decade in the Unites States and about 5% internationally during the second decade. There remains a large incidence range both in the United States (1-12.5%) and internationally (up to 17%). Poor compliance with daily topical antibiotics is an important risk factor. While Gram-positive organisms remained dominant, fungal infections emerged during the second decade. CONCLUSIONS: Daily prophylactic topical antibiotics have dramatically reduced the endophthalmitis incidence. Although Gram-positive organisms are the most common aetiology, antimicrobials must be inclusive of Gram-negative organisms. Selection of prophylactic regimens should be tailored to local antibiotic susceptibility patterns, be cost-effective, and should not promote the emergence of antimicrobial resistance. An example of a broad-spectrum, low-cost prophylactic option for non-autoimmune patients includes trimethoprim/polymyxinB once daily.
Birsner AE, Benny O, D'Amato RJ. The corneal micropocket assay: a model of angiogenesis in the mouse eye. J Vis Exp 2014;(90)Abstract
The mouse corneal micropocket assay is a robust and quantitative in vivo assay for evaluating angiogenesis. By using standardized slow-release pellets containing specific growth factors that trigger blood vessel growth throughout the naturally avascular cornea, angiogenesis can be measured and quantified. In this assay the angiogenic response is generated over the course of several days, depending on the type and dose of growth factor used. The induction of neovascularization is commonly triggered by either basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). By combining these growth factors with sucralfate and hydron (poly-HEMA (poly(2-hydroxyethyl methacrylate))) and casting the mixture into pellets, they can be surgically implanted in the mouse eye. These uniform pellets slowly-release the growth factors over five or six days (bFGF or VEGF respectively) enabling sufficient angiogenic response required for vessel area quantification using a slit lamp. This assay can be used for different applications, including the evaluation of angiogenic modulator drugs or treatments as well as comparison between different genetic backgrounds affecting angiogenesis. A skilled investigator after practicing this assay can implant a pellet in less than 5 min per eye.
Bleier BS, Healy DY, Chhabra N, Freitag S. Compartmental endoscopic surgical anatomy of the medial intraconal orbital space. Int Forum Allergy Rhinol 2014;4(7):587-91.Abstract

BACKGROUND: Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. METHODS: This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. RESULTS: A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. CONCLUSION: The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face.

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