2019

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Ing E, Pagnoux C, Torun N. Advances in the diagnosis of giant cell arteritis. Curr Opin Ophthalmol 2019;30(6):407-411.Abstract
PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.
Ing EB, Miller NR, Ten Hove M, Torun N. Diplopia and Giant Cell Arteritis. J Neuroophthalmol 2019;39(4):546-547.
Ing EB, Wang DN, Kirubarajan A, Benard-Seguin E, Ma J, Farmer JP, Belliveau MJ, Sholohov G, Torun N. Systematic Review of the Yield of Temporal Artery Biopsy for Suspected Giant Cell Arteritis. Neuroophthalmology 2019;43(1):18-25.Abstract
PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The was 92%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012,  = 0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.
Ing E, Sambhi G, Torun N, Pagnoux C. Comments on the giant cell arteritis probability score. Clin Exp Rheumatol 2019;
Inomata T, Nakamura M, Iwagami M, Shiang T, Yoshimura Y, Fujimoto K, Okumura Y, Eguchi A, Iwata N, Miura M, Hori S, Hiratsuka Y, Uchino M, Tsubota K, Dana R, Murakami A. Risk Factors for Severe Dry Eye Disease: Crowdsourced Research Using DryEyeRhythm. Ophthalmology 2019;126(5):766-768.
Inomata T, Iwagami M, Nakamura M, Shiang T, Yoshimura Y, Fujimoto K, Okumura Y, Eguchi A, Iwata N, Miura M, Hori S, Hiratsuka Y, Uchino M, Tsubota K, Dana R, Murakami A. Characteristics and Risk Factors Associated With Diagnosed and Undiagnosed Symptomatic Dry Eye Using a Smartphone Application. JAMA Ophthalmol 2019;Abstract
Importance: The incidence of dry eye disease has increased; the potential for crowdsource data to help identify undiagnosed dry eye in symptomatic individuals remains unknown. Objective: To assess the characteristics and risk factors associated with diagnosed and undiagnosed symptomatic dry eye using the smartphone app DryEyeRhythm. Design, Setting, and Participants: A cross-sectional study using crowdsourced data was conducted including individuals in Japan who downloaded DryEyeRhythm and completed the entire questionnaire; duplicate users were excluded. DryEyeRhythm was released on November 2, 2016; the study was conducted from November 2, 2016, to January 12, 2018. Exposures: DryEyeRhythm data were collected on demographics, medical history, lifestyle, subjective symptoms, and disease-specific symptoms, using the Ocular Surface Disease Index (100-point scale; scores 0-12 indicate normal, healthy eyes; 13-22, mild dry eye; 23-32, moderate dry eye; 33-100, severe dry eye symptoms), and the Zung Self-Rating Depression Scale (total of 20 items, total score ranging from 20-80, with ≥40 highly suggestive of depression). Main Outcomes and Measures: Multivariate-adjusted logistic regression analysis was used to identify risk factors for symptomatic dry eye and to identify risk factors for undiagnosed symptomatic dry eye. Results: A total of 21 394 records were identified in our database; 4454 users, included 899 participants (27.3%) with diagnosed and 2395 participants (72.7%) with undiagnosed symptomatic dry eye, completed all questionnaires and their data were analyzed. A total of 2972 participants (66.7%) were women; mean (SD) age was 27.9 (12.6) years. The identified risk factors for symptomatic vs no symptomatic dry eye included younger age (odds ratio [OR], 0.99; 95% CI, 0.987-0.999, P = .02), female sex (OR, 1.99; 95% CI, 1.61-2.46; P < .001), pollinosis (termed hay fever on the questionnaire) (OR, 1.35; 95% CI, 1.18-1.55; P < .001), depression (OR, 1.78; 95% CI, 1.18-2.69; P = .006), mental illnesses other than depression or schizophrenia (OR, 1.87; 95% CI, 1.24-2.82; P = .003), current contact lens use (OR, 1.27; 95% CI, 1.09-1.48; P = .002), extended screen exposure (OR, 1.55; 95% CI, 1.25-1.91; P < .001), and smoking (OR, 1.65; 95% CI, 1.37-1.98; P < .001). The risk factors for undiagnosed vs diagnosed symptomatic dry eye included younger age (OR, 0.96; 95% CI, 0.95-0.97; P < .001), male sex (OR, 0.55; 95% CI, 0.42-0.72; P < .001), as well as absence of collagen disease (OR, 95% CI, 0.23; 0.09-0.60; P = .003), mental illnesses other than depression or schizophrenia (OR, 0.50; 95% CI, 0.36-0.69; P < .001), ophthalmic surgery other than cataract surgery and laser-assisted in situ keratomileusis (OR, 0.41; 95% CI, 0.27-0.64; P < .001), and current (OR, 0.64; 95% CI, 0.54-0.77; P < .001) or past (OR, 0.45; 95% CI, 0.34-0.58; P < .001) contact lens use. Conclusions and Relevance: This study's findings suggest that crowdsourced research identified individuals with diagnosed and undiagnosed symptomatic dry eye and the associated risk factors. These findings could play a role in earlier prevention or more effective interventions for dry eye disease.
Islam MM, Sharifi R, Mamodaly S, Islam R, Nahra D, AbuSamra DB, Hui PC, Adibnia Y, Goulamaly M, Paschalis EI, Cruzat A, Kong J, Nilsson PH, Argüeso P, Mollnes TE, Chodosh J, Dohlman CH, Gonzalez-Andrades M. Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts. Acta Biomater 2019;96:330-344.Abstract
To address the shortcomings associated with corneal transplants, substantial efforts have been focused on developing new modalities such as xenotransplantion. Xenogeneic corneas are anatomically and biomechanically similar to the human cornea, yet their applications require prior decellularization to remove the antigenic components to avoid rejection. In the context of bringing decellularized corneas into clinical use, sterilization is a crucial step that determines the success of the transplantation. Well-standardized sterilization methods, such as gamma irradiation (GI), have been applied to decellularized porcine corneas (DPC) to avoid graft-associated infections in human recipients. However, little is known about the effect of GI on decellularized corneal xenografts. Here, we evaluated the radiation effect on the ultrastructure, optical, mechanical and biological properties of DPC. Transmission electron microscopy revealed that gamma irradiated decellularized porcine cornea (G-DPC) preserved its structural integrity. Moreover, the radiation did not reduce the optical properties of the tissue. Neither DPC nor G-DPC led to further activation of complement system compared to native porcine cornea when exposed to plasma. Although, DPC were mechanically comparable to the native tissue, GI increased the mechanical strength, tissue hydrophobicity and resistance to enzymatic degradation. Despite these changes, human corneal epithelial, stromal, endothelial and hybrid neuroblastoma cells grew and differentiated on DPC and G-DPC. Thus, GI may achieve effective tissue sterilization without affecting critical properties that are essential for corneal transplant survival.
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Jaffe GJ, Foster SC, Pavesio CE, Paggiarino DA, Riedel GE. Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results. Ophthalmology 2019;126(4):601-610.Abstract
PURPOSE: To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. DESIGN: Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. PARTICIPANTS: One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n = 87) or sham injection (n = 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. METHODS: The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. RESULTS: The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P < 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14% vs. 31%), and reduced systemic (19% vs. 40%) and local (7% vs. 62%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. CONCLUSIONS: Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an office setting.
Jakobiec FA, Wolkow N, Zakka FR, Rubin PAD. Myeloid Sarcoma with Megakaryoblastic Differentiation Arising in the Conjunctiva. Ocul Oncol Pathol 2019;5(1):28-35.Abstract
An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.
Jamshidi F, Place EM, Mehrotra S, Navarro-Gomez D, Maher M, Branham KE, Valkanas E, Cherry TJ, Lek M, MacArthur D, Pierce EA, Bujakowska KM. Contribution of noncoding pathogenic variants to RPGRIP1-mediated inherited retinal degeneration. Genet Med 2019;21(3):694-704.Abstract
PURPOSE: With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet the genetic cause of disease cannot be identified using exon-based sequencing for a significant portion of patients. We hypothesized that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and evaluated patients with single coding pathogenic variants in RPGRIP1 to test this hypothesis. METHODS: IRD families underwent targeted panel sequencing. Unsolved cases were explored by exome and genome sequencing looking for additional pathogenic variants. Candidate pathogenic variants were then validated by Sanger sequencing, quantitative polymerase chain reaction, and in vitro splicing assays in two cell lines analyzed through amplicon sequencing. RESULTS: Among 1722 families, 3 had biallelic loss-of-function pathogenic variants in RPGRIP1 while 7 had a single disruptive coding pathogenic variants. Exome and genome sequencing revealed potential noncoding pathogenic variants in these 7 families. In 6, the noncoding pathogenic variants were shown to lead to loss of function in vitro. CONCLUSION: Noncoding pathogenic variants were identified in 6 of 7 families with single coding pathogenic variants in RPGRIP1. The results suggest that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and RPGRIP1-mediated IRDs are more common than previously thought.
Jiao C, Eliott D, Spee C, He S, Wang K, Mullins RF, Hinton DR, Sohn EH. APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective Trial. Report No. 2. Retina 2019;39(2):265-273.Abstract
PURPOSE: We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy. METHODS: Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed. RESULTS: High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31-CTGF and cytokeratin-VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF. CONCLUSION: Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.
Jonas RA, Ung L, Rajaiya J, Chodosh J. Mystery Eye: Human Adenovirus and the Enigma of Epidemic Keratoconjunctivitis. Prog Retin Eye Res 2019;:100826.Abstract
Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden.
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Kahloun R, Khairallah M, Resnikoff S, Cicinelli MV, Flaxman SR, Das A, Jonas JB, Keeffe JE, Kempen JH, Leasher J, Limburg H, Naidoo K, Pesudovs K, Silvester AJ, Tahhan N, Taylor HR, Wong TY, Bourne RRA, of the of Study VLEGGBD. Prevalence and causes of vision loss in North Africa and Middle East in 2015: magnitude, temporal trends and projections. Br J Ophthalmol 2019;103(7):863-870.Abstract
BACKGROUND: To assess the prevalence and causes of vision impairment in North Africa and the Middle East (NAME) from 1990 to 2015 and to forecast projections for 2020. METHODS: Based on a systematic review of medical literature, the prevalence of blindness (presenting visual acuity (PVA) <3/60 in the better eye), moderate and severe vision impairment (MSVI; PVA <6/18 but ≥3/60) and mild vision impairment (PVA <6/12 but ≥6/18) was estimated for 2015 and 2020. RESULTS: The age-standardised prevalence of blindness and MSVI for all ages and genders decreased from 1990 to 2015, from 1.72 (0.53-3.13) to 0.95% (0.32%-1.71%), and from 6.66 (3.09-10.69) to 4.62% (2.21%-7.33%), respectively, with slightly higher figures for women than men. Cataract was the most common cause of blindness in 1990 and 2015, followed by uncorrected refractive error. Uncorrected refractive error was the leading cause of MSVI in the NAME region in 1990 and 2015, followed by cataract. A reduction in the proportions of blindness and MSVI due to cataract, corneal opacity and trachoma is predicted by 2020. Conversely, an increase in the proportion of blindness attributable to uncorrected refractive error, glaucoma, age-related macular degeneration and diabetic retinopathy is expected. CONCLUSIONS: In 2015 cataract and uncorrected refractive error were the major causes of vision loss in the NAME region. Proportions of vision impairment from cataract, corneal opacity and trachoma are expected to decrease by 2020, and those from uncorrected refractive error, glaucoma, diabetic retinopathy and age-related macular degeneration are predicted to increase by 2020.
Kang JH, Boumenna T, Stein JD, Khawaja A, Rosner BA, Wiggs JL, Pasquale LR. Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma. JAMA Ophthalmol 2019;Abstract
Importance: The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. Objective: To assess the association of elevated cholesterol levels and statin use with incident POAG. Design, Setting, and Participants: This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Exposures: Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Main Outcomes and Measures: Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Results: Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction). Conclusions and Relevance: Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.
Kavitha S, Ramulu PY, Venkatesh R, Palaniswamy K, Kader MA, Raman GV, Rajendrababu S, Zebardast N. Resolution of Visual Dysphotopsias after Laser Iridotomy: Six-Month Follow-up. Ophthalmology 2019;126(3):469-471.e1.
Kaye R, Botten N, Lippestad M, Li D, Hodges RR, Utheim TP, Serhan CN, Dartt DA. Resolvin D1, but not resolvin E1, transactivates the epidermal growth factor receptor to increase intracellular calcium and glycoconjugate secretion in rat and human conjunctival goblet cells. Exp Eye Res 2019;180:53-62.Abstract
PURPOSE: To identify interactions of the epidermal growth factor receptor (EGFR) with the pro-resolving mediator receptors for RvD1 and RvE1 to stimulate an increase in intracellular [Ca] ([Ca]) and mucin secretion from cultured human and rat conjunctival goblet cells. METHODS: Goblet cells from human and rat conjunctiva were grown in culture using RPMI media. Cultured goblet cells were pre-incubated with inhibitors, and then stimulated with RvD1, RvE1, EGF or the cholinergic agonist carbachol (Cch). Increase in [Ca] was measured using fura-2/AM. Goblet cell secretion was measured using an enzyme-linked lectin assay with UEA-1. Western blot analysis was performed with antibodies against AKT and ERK 1/2. RESULTS: In cultured human conjunctival goblet cells RvE1 -stimulated an increase in [Ca]. RvD1-, but not the RvE1-, stimulated increase in [Ca] and mucin secretion was blocked by the EGFR inhibitor AG1478 and siRNA for the EGFR. RvD1-, but not RvE1-stimulated an increase in [Ca] that was also inhibited by TAPI-1, an inhibitor of the matrix metalloprotease ADAM 17. Inhibition of the EGFR also blocked RvD1-stimulated increase in AKT activity and both RvD1-and RvE1-stimulated increase in ERK 1/2 activity. Pretreatment with either RvD1 or RvE1 did not block the EGFR-stimulated increase in [Ca]. CONCLUSIONS: We conclude that in cultured rat and human conjunctival goblet cells, RvD1 activates the EGFR, increases [Ca], activates AKT and ERK1/2 to stimulate mucin secretion. RvE1 does not transactivate the EGFR to increase [Ca] and stimulate mucin secretion, but does interact with the receptor to increase ERK 1/2 activity.
Keeffe JE, Casson RJ, Pesudovs K, Taylor HR, Cicinelli MV, Das A, Flaxman SR, Jonas JB, Kempen JH, Leasher J, Limburg H, Naidoo K, Silvester AJ, Stevens GA, Tahhan N, Wong TY, Resnikoff S, Bourne RRA, of the of Study VLEGGBD. Prevalence and causes of vision loss in South-east Asia and Oceania in 2015: magnitude, temporal trends and projections. Br J Ophthalmol 2019;103(7):878-884.Abstract
BACKGROUND: To assess prevalence and causes of vision impairment in South-east Asia and Oceania regions from 1990 to 2015 and to forecast the figures for 2020. METHODS: Based on a systematic review of medical literature, prevalence of blindness (presenting visual acuity (PVA) <3/60 in the better eye), moderate and severe vision impairment (MSVI; PVA <6/18 but ≥3/60), mild vision impairment (PVA <6/12 but ≥6/18) and near vision impairment (>N5 or N8 in the presence of normal vision) were estimated for 1990, 2010, 2015 and 2020. RESULTS: The age-standardised prevalence of blindness for all ages and both genders was higher in the Oceania region but lower for MSVI when comparing the subregions. The prevalence of near vision impairment in people≥50 years was 41% (uncertainty interval (UI) 18.8 to 65.9). Comparison of the data for 2015 with 2020 predicts a small increase in the numbers of people affected by blindness, MSVI and mild VI in both subregions. The numbers predicted for near VI in South-east Asia are from 90.68 million in 2015 to 102.88 million in 2020. The main causes of blindness and MSVI in both subregions in 2015 were cataract, uncorrected refractive error, glaucoma, corneal disease and age-related macular degeneration. There was no trachoma in Oceania from 1990 and decreasing prevalence in South-east Asia with elimination predicted by 2020. CONCLUSIONS: In both regions, the main challenges for eye care come from cataract which remains the main cause of blindness with uncorrected refractive error the main cause of MSVI. The trend between 1990 and 2015 is for a lower prevalence of blindness and MSVI in both regions.
Kempen JH, Tekle-Haimanot R, Hunduma L, Alemayehu M, Pistilli M, Abashawl A, Lawrence SD, Alemayehu W. Fluorometholone 0.1% as Ancillary Therapy for Trachomatous Trichiasis Surgery: Randomized Clinical Trial. Am J Ophthalmol 2019;197:145-155.Abstract
PURPOSE: To assess the hypothesis that fluorometholone 0.1% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. DESIGN: Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. METHODS: Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1% twice daily for 4 weeks, 4 times daily for 4 weeks, 4 times daily for 8 weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs ≥5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. RESULTS: Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1%) completed 1 year's follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation ≥ 30 mm Hg (to 37 mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3% of placebo eyes vs 17.7%, 19.6%, and 23.2% among the respective fluorometholone groups (P = .29 comparing placebo vs all active treatments combined). CONCLUSIONS: The results suggest fluorometholone 0.1% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4 weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.
Khateb S, Nassisi M, Bujakowska KM, Méjécase C, Condroyer C, Antonio A, Foussard M, Démontant V, Mohand-Saïd S, Sahel J-A, Zeitz C, Audo I. Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B. JAMA Ophthalmol 2019;Abstract
Importance: A precise phenotypic characterization of retinal dystrophies is needed for disease modeling as a basis for future therapeutic interventions. Objective: To compare genotype, phenotype, and structural changes in patients with rod-cone dystrophy (RCD) associated with mutations in PDE6A or PDE6B. Design, Setting, and Participants: In a retrospective cohort study conducted in Paris, France, from January 2007 to September 2017, 54 patients from a cohort of 1095 index patients with RCD underwent clinical examination, including personal and familial history, best-corrected visual acuity (BCVA), color vision, slitlamp examination, full-field electroretinography, kinetic visual fields (VFs), retinophotography, optical coherence tomography, near-infrared fundus autofluorescence, and short-wavelength fundus autofluorescence imaging. Genotyping was performed using microarray analysis, targeted next-generation sequencing, and Sanger sequencing validation with familial segregation when possible. Data were analyzed from September 1, 2017, to February 1, 2018. Clinical variables were subsequently analyzed in 2018. Main Outcomes and Measures: Phenotype and genotype comparison of patients carrying mutations in PDE6A or PDE6B. Results: Of the 54 patients included in the study, 19 patients of 17 families (11 women [58%]; mean [SD] age at diagnosis, 14.83 [10.63] years) carried pathogenic mutations in PDE6A, and 35 patients of 26 families (17 women [49%]; mean [SD] age at diagnosis, 21.10 [11.56] years) had mutations in PDE6B, accounting for prevalences of 1.6% and 2.4%, respectively. Among 49 identified genetic variants, 14 in PDE6A and 15 in PDE6B were novel. Overall, phenotypic analysis revealed no substantial differences between the 2 groups except for night blindness as a presenting symptom that was noted to be more prevalent in the PDE6A than PDE6B group (80% vs 37%, respectively; P = .005). The mean binocular BCVA and VF decrease over time (measured as mean individual slopes coefficients) was comparable between patients with PDE6A and PDE6B mutations: 0.04 (0.12) vs 0.02 (0.05) for BCVA (P = .89) and 14.33 (7.12) vs 13.27 (6.77) for VF (P = .48). Conclusions and Relevance: Mutations in PDE6A and PDE6B accounted for 1.6% and 2.4%, respectively, in a cohort of French patients with RCD. The functional and structural findings reported may constitute the basis of disease modeling that might be used for better prognostic estimation and candidate selection for photoreceptor therapeutic rescue.
Kheirkhah A, Coco G, Satitpitakul V, Pham TT, Dana R. Limbal and Conjunctival Epithelial Thickness in Ocular Graft-Versus-Host Disease. Cornea 2019;38(10):1286-1290.Abstract
PURPOSE: To compare the thickness of the limbal epithelium (LE) and the bulbar conjunctival epithelium (BCE) between patients with dry eye disease (DED) with and without ocular graft-versus-host disease (GVHD). METHODS: This cross-sectional study enrolled 40 patients with moderate to severe DED including 20 with and 20 without chronic ocular GVHD. All patients had a comprehensive clinical ophthalmic assessment. Moreover, the thickness of the LE and BCE in both nasal and temporal regions of both eyes was measured using spectral domain optical coherence tomography. RESULTS: The average LE thickness in all patients with dry eye (GVHD and non-GVHD) was 65.8 ± 11.9 μm temporally and 69.7 ± 11.1 μm nasally (P = 0.02). The average BCE thickness was 55.8 ± 11.4 μm temporally and 60.1 ± 11.0 μm nasally (P = 0.03). There were no statistically significant differences between GVHD and non-GVHD groups in LE thickness (69.6 ± 11.7 vs. 66.1 ± 6.2 μm, respectively, P = 0.31) or BCE thickness (58.9 ± 9.6 vs. 57.3 ± 9.8 μm, respectively, P = 0.82). There was a significant correlation between LE thickness and BCE thickness (P = 0.01, Rs = 0.41). A statistically significant negative correlation was also observed between LE thickness and age (P = 0.002, Rs = -0.35). There were no significant correlations between the thickness of the LE or BCE and other clinical parameters. CONCLUSIONS: No difference exists in the thickness of the ocular surface epithelia between dry eyes with and without ocular GVHD, which would suggest that these epithelial changes may be independent of the underlying etiology and possibly only reflect the disease severity. Furthermore, there are regional variations in the thickness of the ocular surface epithelia in patients with DED.

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