2016

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Murphy RM, Bakir B, O'Brien C, Wiggs JL, Pasquale LR. Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis. J Glaucoma 2016;25(2):e99-e105.Abstract

PURPOSE: We performed a literature synthesis to identify the full spectrum of compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma (2° ACG). METHODS: Systematic PubMed literature review identified relevant bilateral 2° ACG case reports. We evaluated these reports with both the Naranjo adverse drug reaction probability scale to assess the causality of reported drug reactions and a 2° ACG scale scoring system we developed to determine the likelihood that the event represented bilateral 2° ACG. Two independent graders performed these analyses and their scores were averaged for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction was considered definite if the score was ≥9, probable if 5 to 8, possible if 1 to 4, and doubtful if ≤0. The 2° ACG score ranges from 0 to 7. We considered a 2° ACG score of ≥4 as evidence of significant likelihood that the drug reaction represented bilateral 2° ACG. RESULTS: No drug had a definite Naranjo score, but the following drug entities had probable Naranjo scores and 2° ACG scores ≥4: acetazolamide, "anorexiant mix," bupropion, cabergoline, "ecstasy," escitalopram, flavoxate, flucloxacillin, hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid, methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root chemical analysis revealed that sulfur-containing and non-sulfur-containing compounds contributed to bilateral 2° ACG. CONCLUSIONS: Several compound preparations were implicated in drug-induced bilateral 2° ACG. Treating physicians should be aware that some forms of recreational drug use, which the patient may not admit to, could contribute to this vision-threatening side effect.

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Nagendran ST, Lee GN, Fay A, Lefebvre DR, Sutula FC, Freitag SK. Orbital exenteration: The 10-year Massachusetts Eye and Ear Infirmary experience. Orbit 2016;35(4):199-206.Abstract

The authors report their experience with orbital exenteration surgery at one academic institution over a 10-year period and review the literature. This retrospective cohort study monitored outcomes of all patients who underwent orbital exenteration surgery at Massachusetts Eye and Ear Infirmary between January 2003 and January 2013. Patients with no follow-up data or survival data were excluded from the study. The main outcome measures were surgical complications, disease status of surgical margins, need for adjuvant treatment, local recurrence, metastases and survival. 23 patients with malignancy and 2 with mucormycosis met inclusion criteria for the study. Surgical procedures included non-lid sparing total exenteration (44%), lid-sparing total exenteration (32%), non-lid sparing partial exenteration (8%) and lid-sparing partial exenteration (16%). 44% underwent additional extra-orbital procedures. Survival rates were 72% at 1 year, 48% at 3 years, and 37% at 5 years. Of patients with malignancies, 48% had clear margins after exenteration. There was no statistically significant difference in survival between patients with negative surgical margins compared to positive margins (p = 0.12). Mortality was highest in patients with melanoma (85.7%) and lowest in patients with non-squamous cell lid malignancies (0%). Our study suggests that the type of disease has a much greater impact on the survival of patients undergoing exenteration surgery than the type of exenteration surgery or the disease status of surgical margins. Patients with non-squamous cell lid malignancies and localized orbital disease have the best prognosis for tumor eradication from this radical and highly disfiguring surgery.

Naseripour M, Aghaei H, Sedaghat A, Kheirkhah A, Jaberi R, Azma Z. Corneal Patch Graft: A New Approach for Scleral Necrosis Secondary to Plaque Radiotherapy. Cornea 2016;35(4):565-8.Abstract

PURPOSE: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management. METHODS: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye. RESULTS: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 ± 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 ± 7.9 months (range, 20-39 months). CONCLUSIONS: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy.

Noseda R, Bernstein CA, Nir R-R, Lee AJ, Fulton AB, Bertisch SM, Hovaguimian A, Cestari DM, Saavedra-Walker R, Borsook D, Doran BL, Buettner C, Burstein R. Migraine photophobia originating in cone-driven retinal pathways. Brain 2016;139(Pt 7):1971-86.Abstract

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

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Olivares AM, Moreno-Ramos OA, Haider NB. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases. J Exp Neurosci 2015;9(Suppl 2):93-121.Abstract

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

Oray M, Abusamra K, Ebrahimiadib N, Meese H, Foster SC. Long-term side effects of glucocorticoids. Expert Opin Drug Saf 2016;15(4):457-65.Abstract

INTRODUCTION: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. AREAS COVERED: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. EXPERT OPINION: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

Oray M, Khachatryan N, Ebrahimiadib N, Abusamra K, Lee S, Foster SC. Ocular morbidities of juvenile idiopathic arthritis-associated uveitis in adulthood: results from a tertiary center study. Graefes Arch Clin Exp Ophthalmol 2016;254(9):1841-9.Abstract

PURPOSE: To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. METHODS: Medical records were reviewed for patients with JIA-associated uveitis who were >16 years old at the final visit (the last visit prior to data collection). RESULTS: In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27 years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28 %) and 20 (15 %), respectively; at least one ocular complication was present in 72 % of eyes. Band keratopathy was the most frequent complication (42 %), followed by cataract (25 %), posterior synechiae (22 %), maculopathy (22 %), ocular hypertension (13 %), and hypotony (5 %). At the final visit, patients who were >16 years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16 years of age. Ongoing inflammation at the final visit was noted in 40 patients (52 %). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. CONCLUSIONS: JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.

Oray M, Meese H, Foster SC. Diagnosis and management of non-infectious immune-mediated scleritis: current status and future prospects. Expert Rev Clin Immunol 2016;12(8):827-37.Abstract

Scleritis is an inflammatory process of the sclera and adjacent tissues with a wide spectrum of clinical presentations and co-morbidities. Careful clinical history taking, detailed ocular examination, and appropriate investigation for likelihood of an underlying systemic disease are essential for diagnosis. Treatment can be quite challenging in some cases. Conventional therapy with corticosteroids and immunosuppressive agents may not be sufficient to control ocular inflammation in refractory patients. In such cases new therapeutic agents, which have a more targeted and sustained effect on the immune response, so-called biologic response modifiers, are being used. This review focuses on both diagnosis and therapeutic options including traditional and emerging therapies of non-infectious scleritis.

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Pan J, Liu S, Farkas M, Consugar M, Zack DJ, Kozak I, Arevalo FJ, Pierce E, Qian J, Al Kahtani E. Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes. Mol Vis 2016;22:636-45.Abstract

PURPOSE: The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes. METHODS: A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups. RESULTS: Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7% and 91.5%, respectively. CONCLUSIONS: Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings.

Paneghetti L, Ng Y-SE. A novel endothelial-derived anti-inflammatory activity significantly inhibits spontaneous choroidal neovascularisation in a mouse model. Vasc Cell 2016;8:2.Abstract

BACKGROUND: Endothelial cells (EC) grown on collagen particles inhibit intimal hyperplasia in animal models when applied perivascularly, and this effect appears to be, at least in part, the result of EC-derived soluble factors that suppress local vascular inflammation. To elucidate the molecular basis of the therapeutic effects of EC grown on collagen particles, the anti-inflammatory activity of conditioned medium from these cells was characterized. METHODS: Human aortic EC (HAEC) and, for chromatin immunoprecipitation assays, human umbilical vein EC (HUVEC) were treated with tumor necrosis factor alpha (TNFα) in the presence of conditioned medium generated by HAEC grown on collagen particles (ECPCM), and the anti-inflammatory effects were evaluated by analysing the expression of the inflammation-related adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The therapeutic activity of ECPCM was studied using the mouse strain JR5558, which develops spontaneous choroidal neovascularisation (CNV) lesions driven by local inflammation. RESULTS: ECPCM significantly suppressed TNFα-induced expression of E-selectin and VCAM-1. ECPCM did not affect the mRNA stability of the two genes, but suppressed TNFα-induced binding of the p65 subunit of NF-kB transcription factor to E-selectin and VCAM-1 promoters. In vivo, systemic ECPCM treatment significantly reduced the CNV area and the recruitment of activated macrophages to the lesions. Characterization of the molecule responsible for the anti-inflammatory activity in ECPCM indicates that it is unlikely to be a protein and that it is not any of the better characterized EC-derived anti-inflammatory molecules. CONCLUSIONS: Medium conditioned by HAEC grown on collagen particles exhibits significant anti-inflammatory activity via inhibition of genes that mediate inflammatory responses in EC.

Papavasileiou E, Davoudi S, Roohipoor R, Cho H, Kudrimoti S, Hancock H, Wilson JG, Andreoli C, Husain D, James M, Penman A, Chen CJ, Sobrin L. Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes. Graefes Arch Clin Exp Ophthalmol 2017;255(3):509-517.Abstract
PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D). METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate. RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95 % confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95 % CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors. CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.
Papavasileiou E, Miller JB, Sobrin L. SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CONVALESCENT PHASE OF TREATED SARCOID CHOROIDAL GRANULOMAS. Retin Cases Brief Rep 2016;10(1):32-6.Abstract

PURPOSE: To report swept-source optical coherence tomography findings of sarcoid choroidal granulomas in the posttreatment convalescent stage of disease. PATIENTS/METHODS: The authors retrospectively reviewed charts from patients with sarcoid-related choroidal granulomas and recorded pertinent examination and imaging findings. Swept-source optical coherence tomography was performed using the DRI 3D-OCT-1 Atlantis (Topcon) over the areas of previous choroidal granulomas after the patients had been treated. RESULTS: Three patients with sarcoid choroidal granulomas were imaged with swept-source optical coherence tomography. Findings included loss or alteration of choroidal architecture, subretinal fibrosis, and outer retinal tubulations in the areas of the sarcoid granulomas after treatment. In one case with an associated choroidal neovascular membrane, there was also disruption of Bruch membrane and loss of normal choroidal vascular network in the area of the lesion. CONCLUSION: Swept-source optical coherence tomography demonstrated significant anatomical sequelae that persisted after treatment of sarcoid granulomas. To the best of the authors' knowledge, this is the first report of outer retinal tubulations over healed sarcoid granulomas.

Papavasileiou E, Prasad S, Freitag SK, Sobrin L, Lobo A-M. Ipilimumab-induced Ocular and Orbital Inflammation-A Case Series and Review of the Literature. Ocul Immunol Inflamm 2016;24(2):140-6.Abstract

PURPOSE: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy. METHODS: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions. RESULTS: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy. CONCLUSIONS: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.

Park JG, Tischfield MA, Nugent AA, Cheng L, Di Gioia SA, Chan W-M, Maconachie G, Bosley TM, Summers GC, Hunter DG, Robson CD, Gottlob I, Engle EC. Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects. Am J Hum Genet 2016;98(6):1220-7.Abstract

Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.

Park-Windhol C, D'Amore PA. Disorders of Vascular Permeability. Annu Rev Pathol 2016;11:251-81.Abstract

The endothelial barrier maintains vascular and tissue homeostasis and modulates many physiological processes, such as angiogenesis. Vascular barrier integrity can be disrupted by a variety of soluble permeability factors, and changes in barrier function can exacerbate tissue damage during disease progression. Understanding endothelial barrier function is critical for vascular homeostasis. Many of the signaling pathways promoting vascular permeability can also be triggered during disease, resulting in prolonged or uncontrolled vascular leak. It is believed that recovery of the normal vasculature requires diminishing this hyperpermeable state. Although the molecular mechanisms governing vascular leak have been studied over the last few decades, recent advances have identified new therapeutic targets that have begun to show preclinical and clinical promise. These approaches have been successfully applied to an increasing number of disease conditions. New perspectives regarding how vascular leak impacts the progression of various diseases are highlighted in this review.

Pasquale LR, Borrás T, Fingert JH, Wiggs JL, Ritch R. Exfoliation syndrome: assembling the puzzle pieces. Acta Ophthalmol 2016;94(6):e505-12.Abstract

PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. CONCLUSION: Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS.

Pasquale LR, Hyman L, Wiggs JL, Rosner BA, Joshipura K, McEvoy M, McPherson ZE, Danias J, Kang JH. Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study. Ophthalmology 2016;123(11):2318-2327.Abstract

PURPOSE: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. DESIGN: Prospective cohort study. PARTICIPANTS: Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. METHODS: By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. MAIN OUTCOME MEASURES: During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). CONCLUSIONS: Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.

Patel AV, Lane AM, Morrison MA, Trofimov AV, Shih HA, Gragoudas ES, Kim IK. Visual Outcomes after Proton Beam Irradiation for Choroidal Melanomas Involving the Fovea. Ophthalmology 2016;123(2):369-77.Abstract

PURPOSE: To report visual outcomes in patients undergoing proton beam irradiation of tumors located within 1 disc diameter of the fovea. DESIGN: Retrospective review. PARTICIPANTS: Patients with choroidal melanoma involving the fovea treated with proton beam therapy between 1975 and 2009. METHODS: Three hundred fifty-one patients with choroidal melanomas located 1 disc diameter (DD) or less from the fovea and more than 1 DD away from the optic nerve were included in this study. In a subgroup of 203 of the patients with small and medium choroidal melanomas, the effect of a reduced dose of radiation, 50 Gy (relative biological effectiveness [RBE]) versus 70 Gy (RBE), on visual outcomes was analyzed. The Kaplan-Meier method and Cox regression analysis were performed to calculate cumulative rates of vision loss and to assess risk factors for vision loss, respectively. MAIN OUTCOME MEASURES: Visual acuity and radiation complications, which included radiation maculopathy, papillopathy, retinal detachment, and rubeosis, were assessed. RESULTS: Three hundred fifty-one patients were included in this study with a mean follow-up time of 68.7 months. More than one-third of patients (35.5%) retained 20/200 or better vision 5 years after proton beam irradiation. For those patients with a baseline visual acuity of 20/40 or better, 16.2% of patients retained this level of vision 5 years after proton beam irradiation. Tumor height less than 5 mm and baseline visual acuity 20/40 or better were associated significantly with a better visual outcome (P < 0.001). More than two-thirds (70.4%) of patients receiving 50 Gy (RBE) and nearly half (45.1%) of patients receiving 70 Gy (RBE) retained 20/200 or better vision 5 years after treatment, but this difference was not significant. Approximately 20% of patients with these smaller macular tumors retained 20/40 vision or better 5 years after irradiation. CONCLUSIONS: The results of this retrospective analysis demonstrate that despite receiving a full dose of radiation to the fovea, many patients with choroidal melanoma with foveal involvement maintain useful vision. A radiation dose reduction from 70 to 50 Gy (RBE) did not seem to increase the proportion of patients who retain usable vision.

Patel AK, Newcomb CW, Liesegang TL, Pujari SS, Suhler EB, Thorne JE, Foster SC, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Sen NH, Artornsombudh P, Kothari S, Kempen JH, for Group SITEDR. Risk of Retinal Neovascularization in Cases of Uveitis. Ophthalmology 2016;123(3):646-54.Abstract

PURPOSE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13 810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26 465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27-0.41). Factors associated with incident NV include age <35 years compared with >35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed >5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within <1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection.

Payal AR, Sola-Del Valle D, Gonzalez-Gonzalez LA, Cakiner-Egilmez T, Chomsky AS, Vollman DE, Baze EF, Lawrence M, Daly MK. American Society of Anesthesiologists classification in cataract surgery: Results from the Ophthalmic Surgery Outcomes Data Project. J Cataract Refract Surg 2016;42(7):972-82.Abstract

PURPOSE: To explore the association of American Society of Anesthesiologists (ASA) classification with cataract surgery outcomes. SETTING: Five Veterans Affairs Medical Centers, United States. DESIGN: Retrospective observational cohort study. METHODS: The study analyzed the outcomes of cataract surgery cases. Corrected distance visual acuity (CDVA), unanticipated events, and vision-related quality of life (VRQL) were assessed using the National Eye Institute Visual Function Questionnaire (NEI-VFQ), comparing ASA classes I through IV. For some analyses, ASA classes I and II were designated as Group A and ASA classes III and IV were designated Group B. RESULTS: Of the 4923 cases, 875 (17.8%) were in Group A, 4032 (81.9%) were in Group B, and 16 (0.3%) had missing data. The mean CDVA and mean composite NEI-VFQ score improved after cataract surgery in both groups (P < .0001); however, Group A had a better mean postoperative CDVA and postoperative VFQ composite scores than Group B (P < .0001, both outcomes). A higher ASA class was associated with an increased risk for 2 unanticipated events; that is, clinically significant macular edema (CSME) (Group A: 4 [0.47%] versus Group B: 50 [1.28%]; adjusted odds ratio [OR], 3.02; 95% confidence interval [CI], 1.02-13.05; P = 0.04) and readmission to the hospital within 30 days (2 [0.23%] versus 56 [1.41%]; OR, 8.26; 95% CI, 1.71-148.62; P = .004) CONCLUSIONS: Among United States veterans, the ASA classification could be an important predictor of VRQL and visual outcomes. In this cohort, it was associated with an increased risk for 2 serious unanticipated events-CSME and readmission to the hospital-both costly, unwanted outcomes. FINANCIAL DISCLOSURE: Dr. Vollman is a consultant to Forsight Vision5. None of the authors has a financial or proprietary interest in any material or method mentioned.

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