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  • Rhegmatogenous Retinal Detachment In Children: Clinical Factors Predictive Of Successful Surgical Repair
    Ophthalmology (IF 7.479) Pub Date : 2018-11-10
    Jesse M. Smith, Laura T. Ward, Justin H. Townsend, Jiong Yan, Andrew M. Hendrick, Blaine E. Cribbs, Steven Yeh, Nieraj Jain, G. Baker Hubbard

    ObjectiveTo describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD).DesignRetrospective interventional case series.Subjects212 eyes of 191 patients, aged 0-18 years, undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow up of 3 months.MethodsPatients were divided into three age groups (0-6 years, 7-12 years, 13-18 years) and comparisons were made using bivariate and multivariable generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time.Main Outcome MeasuresComplete reattachment of the retina at final follow up.ResultsOf a total of 212 eyes, 166 (78%) achieved total reattachment at final follow up. Mean follow up was 36.3 months. RRD associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR] 0.45, 95 % confidence interval [CI] 0.22 - 0.91), while RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR 2.3, 95% CI 1.2 - 4.4). Subtotal RRD was more likely to be successfully repaired than total RRD (OR 3.6, 95% CI 1.5 - 8.4, p = 0.0100), and eyes with previous vitreoretinal surgery were less likely to have successful repair (OR 0.30, 95% CI 0.12 – 0.78, p = 0.0258). There was no significant difference between age groups in the rate of surgical success (p = 0.55). There was a significantly higher success rate with primary scleral buckle (SB) (63%, OR 2.2, 95% CI 1.1- 4.5) and combined scleral buckle/vitrectomy (SB/PPV) (68%, OR 2.3 95% CI 1.1-5.1) compared to vitrectomy (PPV) alone (51%).ConclusionsMost pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to present with RRD involving the macula but there was no difference between age groups in successful reattachment at final follow up. Primary PPV had a lower rate of success than SB or combined SB/PPV.

    更新日期:2018-11-10
  • Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-label Extension of RIDE and RISE Studies
    Ophthalmology (IF 7.479) Pub Date : 2018-11-09
    Jennifer K. Sun, Pin-wen Wang, Sarah Taylor, Zdenka Haskova

    Objective To evaluate durability of diabetic retinopathy (DR) improvements after a change in ranibizumab dosing from monthly to individualized pro re nata (PRN) therapy. Design Pooled analysis of the open-label extension (OLE) of RIDE/RISE (NCT00473382/NCT00473330) patients with DR and diabetic macular edema (DME). Participants Patients who completed 36-month participation in RIDE/RISE and entered the OLE. Methods In the RIDE/RISE studies, patients (N = 759) were randomized 1:1:1 to ranibizumab 0.3 mg monthly, 0.5 mg monthly, or monthly sham injections with rescue macular laser available after 6 months, per protocol-specified criteria. After 24 months, sham patients crossed over to ranibizumab 0.5 mg monthly. After 36 months in the core studies, patients in the OLE (n = 500) could receive ranibizumab 0.5 mg through an individualized PRN dosing regimen based on predefined DME re-treatment criteria. DR severity was evaluated photographically using the Early Treatment Diabetic Retinopathy Study DR severity scale. Main Outcome Measure Change in DR severity from months 36 to 48 by re-treatment status. Results Among patients who entered the OLE, 121/500 (24%) did not require additional ranibizumab injections. In total, 442 patients had evaluable DR outcomes during the OLE; 367 had evaluable DR at months 36 and 48. Among patients not requiring ranibizumab re-treatment from months 36 to 48 (88/367), 57% to 78%, 0% to 7%, and 22% to 36% experienced DR severity stability, ≥2-step improvement, and ≥2-step worsening, respectively. Among patients requiring ranibizumab re-treatment (279/367), 84% to 94%, 2%, and 3% to 14% experienced DR severity stability, ≥2-step improvement, and ≥2-step worsening, respectively. On average, vision improvements were maintained during the OLE regardless of change in DR severity. Conclusions DR severity improvements with ranibizumab were maintained in the majority of patients in the OLE after switching from ranibizumab monthly to an individualized best-corrected visual acuity– and optical coherence tomography–based ranibizumab 0.5 mg PRN dosing regimen. Because nearly one-third of OLE patients not requiring further therapy for DME experienced DR worsening, once DME resolves, patients should be watched carefully for worsening of DR and possible need for more frequent follow-up and/or treatment of vision-threatening disease with anti-VEGF or other modalities.

    更新日期:2018-11-09
  • 24-Hour Intraocular Pressure Control with Fixed-dose Combination Brinzolamide 1%/Brimonidine 0.2%: A Multicenter, Randomized Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-11-04
    Robert N. Weinreb, Jason Bacharach, Robert D. Fechtner, Malik Y. Kahook, David Wirta, Steve Burmaster, Xiangyi Meng, Douglas A. Hubatsch

    Purpose To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. Design Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and non-academic sites in the USA. Participants Subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT) aged ≥18 years, with mean baseline IOP measurements in at least one eye of ≥21 and <28 mmHg. Methods Duplicate, mean pneumatonometer IOP measurements were collected every 2 hours over a 24-hour period in controlled light conditions in overnight facilities. Daytime (8 AM–8 PM) and nocturnal (10 PM–6 AM) IOP measurements were collected in a sitting or supine position, respectively. Baseline 24-hour IOP was measured in untreated subjects after a washout phase (up to 4 weeks) and eligibility phase. Following the baseline visit, subjects were randomized 1:1 to receive masked BBFC or Vehicle, one drop three times daily (8 AM, 3 PM, 10 PM) for 4 weeks. At Week 4, IOP measurements were repeated in both groups under the same conditions. Main Outcome Measure Mean change from Baseline in 24-hour IOP at Week 4. Results Of 125 subjects randomized, 123 (98%; BBFC, n=62; Vehicle, n=61) completed the study. No subjects randomized to BBFC discontinued from the study. At Week 4, BBFC-treated eyes had significantly reduced mean 24-hour IOP vs Vehicle (least squares mean difference [95% confidence interval]: -2.5 [-3.3, -1.7]; P < 0.001); daytime (-3.4 [ 4.3, -2.6]; P < 0.001) and nocturnal (-1.2 [-2.3, 0.0]; P = 0.053) reductions were observed. Mean change from Baseline was significantly different between BBFC- and Vehicle-treated eyes at all day-time points and three of five nocturnal time points (10 PM, 12 AM, 6 AM; secondary endpoint). The frequency of adverse events was similar between treatment groups; in the BBFC arm, ocular hyperemia, corneal abrasion, and dysgeusia were the most frequently reported, consistent with events described in the drug label. Conclusions This first large, multicenter study of 24-hour IOP control with BBFC met its primary endpoint; BBFC demonstrated significantly superior 24-hour IOP-lowering efficacy vs Vehicle following 4 weeks of three-times-daily treatment in subjects with OAG or OHT.

    更新日期:2018-11-05
  • The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration
    Ophthalmology (IF 7.479) Pub Date : 2018-10-31
    Robert F. Mullins, Gerald McGwin, Karen Searcey, Mark E. Clark, Elizabeth L. Kennedy, Christine A. Curcio, Edwin M. Stone, Cynthia Owsley

    Objective To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD), and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD. Design Cross-sectional Subjects Older adults aged ≥60 years in normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9). Methods Single nucleotide polymorphisms were genotyped in the CFH and ARMS2 genes using a Taqman assay. RMDA was assessed in one eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking. Main Outcome Measure RIT. Results The sample consisted of 543 participants having both genotype and RIT determination; 408 were in normal macular health and 135 had AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted p=0.0001 and p=0.0023 respectively). For normal subjects the A69S variant in ARMS2 was associated with higher RIT (adjusted p=0.0011), whereas CFH Y402H was not (adjusted p=0.2175). For AMD cases, the A69S variant of ARMS2 and CFH Y402H were associated with higher RIT (adjusted p=0.0182 and p=0.0222 respectively). Those with a greater number of high-risk ARMS2 and CFH alleles had higher RIT, in both normal and AMD groups (adjusted p=0.0002 and p<0.0001 respectively). Conclusions We report a novel association wherein older adults with high risk ARMS2 and CFH genotypes are more likely to have delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those in normal macular health with the ARMS2 A69S allele have delayed RMDA. Understanding ARMS2 function is a research priority.

    更新日期:2018-10-31
  • Pre-operative vision and surgeon volume as predictors of visual outcomes following cataract surgery
    Ophthalmology (IF 7.479) Pub Date : 2018-10-25
    Bobeck S. Modjtahedi, Michaela M. Hull, John Adams, Stephen Munz, Tiffany Q. Luong, Donald S. Fong

    Purpose To evaluate the relationship between pre-operative vision and surgeon volume with visual outcomes following cataract surgery. Design Retrospective cohort study. Subjects Patients > 18 years old enrolled in Kaiser Permanente Southern California health plan that underwent cataract surgery by non-trainee surgeons. Methods Patients who underwent cataract surgery between December 31, 2013 and January 1, 2015 were included. A multivariate analysis using GAMM (Generalized Additive Mixed Models) was performed to determine the relationship between surgeon volume and post-operative visual acuity after controlling for patient age, pre-operative visual acuity, history of diabetes, and history of diabetic retinopathy. Modeling was done for the relationship between pre-operative vision and visual outcomes while controlling for surgeon volume, patient age, history of diabetes, and history of diabetic retinopathy. Main outcome measure Absolute letter change and percentage of patients to achieve of > 5 letter Early Treatment Diabetic Retinopathy Study (ETDRS) gain post-operatively. Results There were 103,920 cataract surgeries performed by 136 surgeons included in this analysis. Patients whose surgeons performed < 91.0 surgeries/year [95% Confidence Interval (CI) 61.1-139, p<0.05] gained fewer letters post-operatively while those whose surgeons performed >91 but < 227 surgeries/year (95% CI 169- ∞, p<0.05) gained more letters than average. Although statistically significant, the difference between the lowest and highest performing groups was approximately 1.25 letters. Surgeons who performed <110 surgeries/year (95% CI 81.7-149, p<0.05) had less patients who gained > 5 letters. Surgeons who performed >110 but <293 surgeries/year (95% CI 232- ∞, p<0.05) were as high as 15-20% more likely to have patients who gained > 5 letters. Patients with pre-operative vision < 74.7 letters (95% CI 74.7-74.8, p<0.05) and < 75.8 letters (95% CI 75.8-75.9, p<0.05) gained more letters and were more likely to gain > 5 letters post-operatively, respectively Conclusion Patients whose vision is approximately 20/32 or worse are more likely to have significant visual gains after cataract surgery. Although statistically significant differences exist in post-operative vision based on surgeon volume, these do not appear to be clinically meaningful. Overall, visual outcomes are clinically and functionally comparable across a wide range of surgeon volumes.

    更新日期:2018-10-26
  • Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Noninfectious Uveitis Affecting the Posterior Segment: 12-Month Results
    Ophthalmology (IF 7.479) Pub Date : 2018-10-25
    Glenn J. Jaffe, Stephen Foster, Carlos Pavesio, Dario Paggiarino, Gerard E. Riedel

    Objective To assess the safety and efficacy of an intravitreal fluocinolone acetonide insert (FAi) to manage inflammation associated with noninfectious posterior uveitis. Design Multi-center, randomized, prospective, doubled-masked, sham-controlled, 3-year, phase 3 clinical trial. Participants A total of 129 participants with recurrent noninfectious posterior uveitis were randomly assigned to FAi (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, optical coherence tomography, 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 FAi versus sham, respectively. Fewer recurrences per study eye (mean of 0.7 versus 2.5), lower incidence of ≥15 letter 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 FAi versus sham, respectively. FAi had higher rates of cataract. Intraocular pressure-lowering treatment use was similar. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. Conclusion Noninfectious posterior uveitis was successfully managed in this study population; FAi eyes had fewer uveitis recurrence episodes, required fewer adjunctive treatments, and had less visual acuity loss compared with sham eyes. FAi treatment had 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. [300/300 words]

    更新日期:2018-10-25
  • A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years of Age
    Ophthalmology (IF 7.479) Pub Date : 2018-10-22
    Jonathan M. Holmes, Ruth E. Manny, Elizabeth L. Lazar, Eileen E. Birch, Krista R. Kelly, Allison I. Summers, Stacy R. Martinson, Aparna Raghuram, Jeffrey D. Colburn, Christine Law, Justin D. Marsh, Derek P. Bitner, Raymond T. Kraker, David K. Wallace,

    Purpose To compare visual acuity (VA) improvement in children aged 7 to 12 years with amblyopia treated with a binocular iPad® game plus continued spectacle correction versus continued spectacle correction alone. Design Multi-center randomized clinical trial Participants One hundred thirty-eight participants aged 7 to 12 years with amblyopia (33 to 72 letters, i.e., approximately 20/200 to 20/40) resulting from strabismus, anisometropia, or both. Participants were required to have at least 16 weeks of optical treatment in spectacles if needed or demonstrate no improvement in amblyopic-eye visual acuity (VA) for at least 8 weeks prior to enrollment. Methods Eligible participants (mean age 9.6 years, mean baseline VA of 59.6 letters, history of prior amblyopia treatment other than spectacles in 96%) were randomly assigned to treatment for 8 weeks with the dichoptic binocular Dig Rush iPad game (prescribed for 1 hour per day 5 days per week) plus spectacle wear if needed (N=69) or continued spectacle correction alone if needed (N=69). Main Outcome Measures Change in amblyopic-eye VA from baseline to 4 weeks, assessed by a masked examiner. Results At 4 weeks, mean amblyopic-eye VA letter score improved from baseline by 1.3 (2-sided 95% confidence interval (CI): 0.1 to 2.6; 0.026 logMAR) with binocular treatment and by 1.7 (2-sided 95% CI: 0.4 to 3.0; 0.034 logMAR) with continued spectacle correction alone. After adjusting for baseline VA, the letter score difference between groups (binocular minus control) was -0.3 (95% CI: -2.2 to 1.5, p=0.71, difference of -0.006 logMAR). No difference in letter scores was observed between groups when the analysis was repeated after 8 weeks of treatment (adjusted mean: -0.1, 98.3% CI: -2.4 to 2.1). For the binocular group, adherence data from the iPad indicated that slightly more than half of the participants (58% and 56%) completed >75% of prescribed treatment by the 4- and 8-week visits, respectively. Conclusions In children aged 7 to <13 years, who have received previous treatment for amblyopia other than spectacles, there was no benefit to visual acuity or stereoacuity from 4 or 8 weeks of treatment with the dichoptic binocular Dig Rush iPad game.

    更新日期:2018-10-22
  • Genetic Architecture of Primary Open Angle Glaucoma in Individuals of African Descent: The African Descent & Glaucoma Evaluation Study (ADAGES) III
    Ophthalmology (IF 7.479) Pub Date : 2018-10-21
    Kent D. Taylor, Xiuqing Guo, Linda M. Zangwill, Jeffrey M. Liebmann, Christopher A. Girkin, Robert M. Feldman, Harvey Dubiner, Yang Hai, Brian C. Samuels, Joseph F. Panarelli, John P. Mitchell, Lama A. Al-Aswad, Sung Chul Park, Celso Tello, Jeremy Cotliar, Rajendra Bansal, Paul A. Sidoti, George A. Cioffi, Robert N. Weinreb

    Objective Find genetic contributions to glaucoma in African Americans. Design Cross-sectional, case-control study. Participants 1875 POAG cases and 1709 controls, self-identified as African Descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGESIII) and Wake Forest School of Medicine. Methods MegaChip genotypes were imputed to Thousand Genomes data. Association of SNPs with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by Receiver Operator Characteristics (ROC-AUC). Main Outcome: POAG defined by visual field loss without other non-ocular conditions (N=1875). Advanced POAG was defined by age-based mean deviation of visual field (N=946). Results 18,281,920 SNPs met imputation quality r2>0.7 and minor allele frequency>0.005. Association of a novel locus, ENO4, was observed for advanced POAG (rs185815146 beta 0.36, SE 0.065, p<3x10-8). For POAG, an AD signal was observed at 9p21 ED POAG signal (rs79721419; p<6.5x10-5) independent of the previously observed 9p21 ED signal (rs2383204; p<2.3x10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934, p<3.9x10-5) was observed, not in LD with the previously reported ED SNP. Additional previously identified loci associated with POAG in AD were: 8q22, AFAP1, TMCO1. An AUC of 0.62 was observed with an unweighted genetic risk score composed of 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC=0.74 and AUC=0.94, respectively. Conclusions A novel association with advanced POAG in the ENO4 locus was putatively identified in subjects of African descent. In addition to this finding, this GWAS in AD POAG subjects contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine-mapping of regions due to shorter average linkage disequilibrium (FNDC3B). While not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

    更新日期:2018-10-22
  • Potential lost productivity resulting from the global burden of myopia: systematic review, meta-analysis and modelling
    Ophthalmology (IF 7.479) Pub Date : 2018-10-17
    Kovin S. Naidoo, Timothy R. Fricke, Kevin D. Frick, Monica Jong, Thomas J. Naduvilath, Serge Resnikoff, Padmaja Sankaridurg

    Topic We estimated the potential global economic productivity loss due to vision impairment (VI) and blindness from uncorrected myopia and myopic macular degeneration (MMD) in 2015. Clinical relevance Understanding the economic burden of VI associated with myopia is critical to addressing myopia as an increasingly prevalent public health problem. Methods We used systematic review and meta-analysis to estimate the number of people with myopia and MMD corresponding to critical visual acuity thresholds. Spectacle correction coverage was analyzed against country-level variables from the year of data collection; variation in spectacle correction was best described by a model based on human development index, with adjustments for urbanization and age. Spectacle correction and myopia data were combined to estimate the number of people with each level of VI from uncorrected myopia. We then applied disability weights, labor force participation rates, employment rates and gross domestic product per capita to estimate the potential productivity lost among individuals with each level and type of VI due to myopia in 2015 in US$. An estimate of care-associated productivity loss was also included. Results People with myopia are less likely to have adequate optical correction if they are older and live in a rural area of a less developed country. The global potential productivity loss associated with the burden of VI in 2015 was estimated at US$244 billion (95% confidence interval US$49 billion – US$697 billion) from uncorrected myopia, and US$6 billion (US$2 billion – US$17 billion) from MMD. Our estimates suggest that the Southeast Asia, South Asia, and East Asia Global Burden of Disease regions bear the greatest potential burden as a proportion of their economic activity, while East Asia bears the greatest potential burden in absolute terms. Conclusion Even under conservative assumptions, the potential productivity loss associated with VI and blindness from uncorrected myopia is substantially greater than the cost of correcting myopia.

    更新日期:2018-10-18
  • DICER1 Syndrome: Characterization of the ocular phenotype in a family-based cohort study
    Ophthalmology (IF 7.479) Pub Date : 2018-10-17
    Laryssa A. Huryn, Amy Turriff, Laura A. Harney, Ann Garrity Carr, Patricia Chevez-Barrios, Dan S. Gombos, Radha Ram, Robert B. Hufnagel, D. Ashley Hill, Wadih M. Zein, Kris Ann P. Schultz, Rachel Bishop, Douglas R. Stewart

    Purpose To characterize the ocular phenotype of DICER1 syndrome Design Prospective, single-center, case-control study Subjects, Participants, and/or Controls One hundred and three patients with an identified germline, pathogenic DICER1 variant (DICER1-carriers) and 69 family control subjects underwent clinical and ophthalmic examination at the National Institutes of Health between 2011 and 2016. Methods All participants were evaluated with a comprehensive ophthalmic exam including best corrected visual acuity, slit-lamp biomicroscopy and a dilated fundus examination. A subset of patients returned for a more detailed evaluation including spectral-domain optical coherence tomography, color fundus photography, fundus autofluorescence imaging, visual field testing, full field electroretinogram and genetic testing for inherited retinal degenerative diseases. Main Outcome Measures Visual acuity and examination findings Results Most DICER1-carriers (97%) maintained a visual acuity of 20/40 or better in both eyes. Twenty three DICER1-carriers (22%) had ocular abnormalities compared with four (6%) family controls (P=0.005). These abnormalities included retinal pigment abnormalities (N=6, 5.8%), increased cup-to-disc ratio (N=5, 4.9%), optic nerve abnormalities (N=2, 1.9%), epiretinal membrane (N=2, 1.9%) and drusen (N=2, 1.9%). Overall, we observed a significant difference (p= 0.03) in the rate of retinal abnormalities in DICER1-carriers (N=11, 11%) vs. controls (N=1; 1.5%). One patient had an unexpected diagnosis of retinitis pigmentosa with a novel variant of unknown significance in PRPF31, and one had optic nerve elevation in the setting of increased intracranial pressure of unclear etiology. Three patients (3%) had DICER1-related ciliary body medulloepithelioma (CBME), two of which were identified during routine examination, a significantly higher rate than that previously reported. Conclusions Ophthalmologists should be aware of the ophthalmic manifestations of the DICER1 syndrome and individuals and families should be counseled on the potential signs and symptoms. We recommend that children with a germline pathogenic variant in DICER1, especially those under the age of 10 years, undergo annual dilated ophthalmic examination, looking for evidence of CBME, signs of increased intracranial pressure and perhaps changes in the retinal pigment epithelium.

    更新日期:2018-10-17
  • Aravind Pseudoexfoliation Study (APEX) - Surgical and First Year Postoperative Results in Eyes Without Phacodonesis and Non-Miotic Pupils
    Ophthalmology (IF 7.479) Pub Date : 2018-10-17
    Aravind Haripriya, Pradeep Y. Ramulu, Shivkumar Chandrashekharan, Rengaraj Venkatesh, Kalpana Narendran, Madhu Shekhar, Rengappa Ramakrishnan, Ravilla D. Ravindran, Alan L. Robin

    Purpose To compare: (1) intraoperative complication rates, (2) one-year visual outcomes, and (3) post-operative complication rates over the first post-operative year in eyes with and without pseudoexfoliation (PEX) undergoing cataract surgery. Design Prospective comparative interventional study Participants Nine-hundred thirty eyes with cataract and uncomplicated PEX (without phacodonesis, clinically shallow anterior chambers, or pupil size < 4mm ) and 476 controls with cataract but without PEX recruited from four centers of the Aravind Eye Care System in Southern India. The PEX and control groups were each separately randomized to receive either a single (SA60AT) or three piece acrylic IOL (MA60AS). The PEX group was also randomized to receive or not receive a capsular tension ring (CTR). Methods All eyes underwent phacoemulsification with IOL implantation and were followed at 1 day, 1 month, 3 months and 1 year after surgery. Main Outcome Measures Association of PEX status on intraoperative complication rates, one-year best corrected visual acuity, and any other complications. Results Mean ages were 63.0 ± 6.9 years and 57.9 ± 7.3 years in the PEX and control groups, respectively (p<0.001). PEX subjects were more likely to be male (p=0.014), have a nuclear opalescence grade>4 (p=0.001) and a pupil <6 mm (p< 0.001) when compared to controls. Intraoperative complication rates were 2.9% and 1.9% in the PEX and control groups, respectively (p=0.29). One year post-operative best-corrected visual acuity was comparable (p=0.09). Complication rates at 1 year were 2.7% and 2.5% in the PEX and control groups (p=0.82). Average endothelial cell loss was 14.7% in PEX group and 12.7% in control group at 1 year (p=0.066) when adjusting for age and nuclear opacity). Conclusions We evaluated PEX eyes without shallow anterior chamber, small pupils or apparent zonulopathy. These may represent eyes with lower risks of complications. Despite smaller pupils and denser cataracts, PEX eyes without clinically apparent preoperative zonulopathy were not at a higher risk of intra or post-operative complications, or worse visual outcomes after cataract surgery.

    更新日期:2018-10-17
  • Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis
    Ophthalmology (IF 7.479) Pub Date : 2018-10-16
    Dyfrig A. Hughes, Giovanna Culeddu, Catrin Plumpton, Eifiona Wood, Andrew D. Dick, Ashley P. Jones, Andrew McKay, Paula R. Williamson, Sandrine Compeyrot Lacassagne, Ben Hardwick, Helen Hickey, Patricia Woo, Michael W. Beresford, Athimalaipet V. Ramanan

    Objectives To investigate the cost-effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with Juvenile Idiopathic Arthritis (JIA-U). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents aged 2 to 18 years with persistently active JIA-U, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE trial [ISRCTN10065623] of methotrexate (up to 25mg per week) with or without fortnightly administered adalimumab (20mg or 40mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main outcome measures Medical costs to the National Health Service in the UK, utility of defined health states, quality-adjusted life years (QALY), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39,316 with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129,025 per QALY gained. The probability of cost-effectiveness at a threshold of £30,000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost-effective. Conclusions Adalimumab is clinically effective in JIA-U, however its cost-effectiveness is not demonstrated compared with methotrexate alone in the UK setting.

    更新日期:2018-10-16
  • Efficacy and Safety of Sarilumab for Noninfectious Uveitis of Posterior Segment: Outcomes From the Phase 2 SATURN Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-10-11
    Jarmila Heissigerová, David Callanan, Marc D. de Smet, Sunil K. Srivastava, Michala Karkanova, Olga Garcia-Garcia, Sibel Kadayifcilar, Yilmaz Ozyazgan, Robert Vitti, Kristine Erickson, Aditya Athanikar, Karen Chu, Namrata Saroj, Preethi A. Sundaram, Rafael Varona, Valerie Corp-dit-Genti, Ronald Buggage, Yenchieh Cheng, Quan Dong Nguyen

    Purpose To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for the treatment of noninfectious uveitis (NIU) of posterior segment. Design Randomized, double-masked, placebo-controlled, phase 2 study. Participants Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or pan-uveitis. Methods Eyes were randomized 2:1 to treatment q2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. Main Outcome Measures Primary endpoint was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale, or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary endpoint was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. Results At week 16, the proportion of sarilumab and placebo patients with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was, respectively, 46.1% versus 30.0% (P=0.2354) based on central reading center assessment of VH, and 64.0% versus 35.0% (P=0.0372) based on investigator assessment of VH. In the subgroup of eyes with VH ≥grade 2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab versus placebo regardless of assessment by central reading center (-2.1 [n=11] versus -1.7 [n=3], respectively; P=0.0255) or investigator (-2.5 [n=19] versus -1.2 [n=11], respectively; P=0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab versus placebo in the overall population (8.9 versus 3.6 letters, respectively; P=0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n=13] versus 2.1 [n=7] letters, respectively; P=0.0517). Corresponding changes in CST were -46.8 versus +2.6 μm (P=0.0683) in the overall population and -112.5 [n=13] versus -1.8 [n=6] μm (P=0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). Conclusions Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

    更新日期:2018-10-12
  • Eight-Year Incidence of Open-Angle Glaucoma in the Tema Eye Survey
    Ophthalmology (IF 7.479) Pub Date : 2018-10-12
    Jean-Claude Mwanza, Samantha E. Tulenko, Keith Barton, Leon W. Herndon, Elizabeth Mathenge, Alyson Hall, Hanna Y. Kim, Graham Hay-Smith, Donald L. Budenz

    Purpose To determine the incidence of open-angle glaucoma (OAG) and its risk factors in the Tema Eye Survey, a population-based eye survey in Ghana, West Africa. Design Longitudinal observational population-based study. Participants One thousand two hundred and five out of 1500 subjects aged 40 years or older, randomly selected from 5603 subjects originally drawn from the population and who had undergone a baseline examination. Method All participants underwent baseline and follow-up ophthalmologic examinations 8 years apart. Glaucoma diagnosis was determined based on the International Society for Geographical and Epidemiologic Ophthalmology criteria. Main Outcome Measures Incidence and odd ratio (OR). Results The response rate was 80.3%. Of 1101 non-glaucomatous participants at baseline who had complete follow-up data, 4.6% (95% CI, 3.7%-5.2%) developed OAG over the 8-year period, or 0.58% (CI, 0.4 to 0.8) per year. The 8-year incidence increased with age from 3.1% in 40-49 years to 7.0% in 60-69 years old subjects. Baseline risk factors for incident OAG were male gender (OR, 2.1; CI, 1.1 to 4.0; P = 0.025), older age relative to 40-49 years old subjects (OR, 2.6; CI, 1.2 to 5.7 for 50-50 years old, OR, 4.3; CI, 2.0 to 8.8 for 60-69 years old, and OR, 6.3; CI, 2.6 to 15.4 for 70 years and older subjects, all P < 0.001), higher IOP (OR, 1.4; CI, 1.1 to 1.8; P < 0.001), larger VCDR (OR, 5.8; CI, 5.2 to 6.6; P < 0.001), and thinner central cornea (OR, 1.2; CI, 1.03 to 1.5; P = 0.013). A separate analysis performed with CCT-based IOP correction did not change the outcome of the associative model of incident glaucoma. Conclusions The incidence of OAG is higher in this population than reported in non-black populations outside Africa. This is important not only in Ghana and probably other West African countries, but also wherever people of the West African diaspora reside. These data enhance our understanding of epidemiology of OAG in this setting, and may serve as reference for public health policy and planning.

    更新日期:2018-10-12
  • Retinopathy Associated with Biallelic Mutations in PYGM (McArdle Disease)
    Ophthalmology (IF 7.479) Pub Date : 2018-10-11
    Omar A. Mahroo, Kamron N. Khan, Genevieve Wright, Zoe Ockrim, Renata S. Scalco, Anthony G. Robson, Adnan Tufail, Michel Michaelides, Ros Quinlivan, Andrew R. Webster
    更新日期:2018-10-11
  • Greater physical activity is associated with slower visual field loss in glaucoma
    Ophthalmology (IF 7.479) Pub Date : 2018-10-10
    Moon Jeong Lee, Jiangxia Wang, David S. Friedman, Michael V. Boland, Carlos G. De Moraes, Pradeep Y. Ramulu

    Objective To determine the association between physical activity levels and the rate of visual field (VF) loss in glaucoma. Design Longitudinal, observational study. Participants Older adults with suspect or manifest glaucoma. Methods Participants wore accelerometers for one week to define average steps per day, minutes of moderate-to-vigorous activity (MVPA) and minutes of non-sedentary activity. All available VF measurements before and after physical activity assessment were retrospectively analyzed to measure rates of VF loss. Main Outcome Measures Pointwise changes in VF sensitivity associated with physical activity measures. Results One hundred forty-one participants (mean age 64.9 ± 5.8 years) were enrolled. Eye mean deviation (MD) at the time of physical activity assessment was -6.6 dB and average steps per day was 5613 ± 3158. The unadjusted average rate of VF loss as measured by pointwise VF sensitivity was 0.36 dB/year (95% CI: -0.37, -0.35). In multivariable models, slower VF loss was observed for patients demonstrating more steps (+0.007 dB/year/1000 daily steps, p<0.001), more moderate-to-vigorous activity (+0.003 dB/year/10 more minutes of MVPA per day, p<0.001), and more non-sedentary activity (+0.007 dB/year/30 more minutes of non-sedentary time per day, p=0.005). Factors associated with a faster rate of VF loss included older age, non-Caucasian race, glaucoma surgery, cataract surgery, and moderate baseline VF damage (-6 dB≥MD>– 12 dB) as opposed to mild VF damage (MD>-6 dB). Similar associations between baseline accelerometer-measured physical activity and rates of VF loss were observed over other time periods (e.g., within 1, 3 and 5 years of activity assessment). Conclusions Increased walking, greater time spent doing moderate-to-vigorous physical activity and more time spent in non-sedentary activity were associated with slower rates of VF loss in a treated population of glaucoma patients, with an additional 5,000 daily steps or 2.6 hours of non-sedentary physical activity decreasing the average rate of VF loss by roughly 10%. Future prospective studies are needed to determine if physical activity can slow VF loss in glaucoma and/or if progressive VF loss results in activity restriction. If the former is confirmed, this would mark physical activity as a novel modifiable risk factor for preventing glaucoma damage.

    更新日期:2018-10-10
  • Uveitis in Patients with Multiple Sclerosis in Clinical Trials of Fingolimod: Incidence, Prevalence and Impact on Disease Course
    Ophthalmology (IF 7.479) Pub Date : 2018-10-10
    Lyndell L. Lim, Diego G. Silva, Tiffany C. Lo, Ronald S. Pimentel, Helmut Butzkueven, Anthony J. Hall

    Objective To determine the incidence and prevalence of uveitis and its effect on multiple sclerosis (MS) disease activity and outcomes in patients with MS who participated in the fingolimod clinical trial program. Design Analysis of pooled data (N = 27 528) from patients enrolled in fingolimod clinical studies and their extensions. Patients were stratified into four cohorts based on the history of uveitis at baseline and uveitis events during the observation period: no history and no uveitis events (‘no uveitis’); history and no uveitis events (‘history’); no history and uveitis events (‘first event’); history and uveitis events (‘recurrent event’). Participants Adult patients diagnosed with relapsing or primary progressive MS. Intervention Patients received fingolimod (0.5, 1.25 or 5 mg/day), placebo or intramuscular interferon beta-1a (IFNβ-1a IM) during the core studies; patients receiving placebo or IFNβ-1a IM were switched to fingolimod 0.5 mg therapy for study extensions. Main Outcome Measures Incidence and prevalence of uveitis, and MS outcome measures including annualized relapse rate (ARR), time to first relapse, change in Expanded Disability Status Scale (EDSS) score from baseline, and proportion of patients with 6-month confirmed disability progression (CDP). Results 189 patients in the analysis population had uveitis. Of these, 162 patients had a history of uveitis (prevalence, 0.59%). Uveitis occurred as a first event in 27 patients (incidence, 0.1 per 100 patient-years) and as a recurrent event in 10 out of 162 patients (prevalence, 6.17%). Patients with uveitis had a significantly shorter time to first relapse (mean, 2.11 vs 8.12 years; P = 0.047) and a significantly higher ARR (0.31 vs 0.21; P = 0.025) than those without uveitis. Mean increase in EDSS score at month 120 and the proportions of patients with 6-month CDP and with EDSS score ≥ 4 during follow-up were similar in patients with uveitis compared with those without uveitis. Conclusions This pooled analysis involving a large patient cohort showed that patients with MS and uveitis had increased MS relapse activity compared with those without uveitis.

    更新日期:2018-10-10
  • Data Driven Scheduling for Improving Patient Efficiency in Ophthalmology Clinics
    Ophthalmology (IF 7.479) Pub Date : 2018-10-10
    Michelle R. Hribar, Abigail E. Huang, Isaac H. Goldstein, Leah G. Reznick, Annie Kuo, Allison R. Loh, Daniel J. Karr, Lorri Wilson, Michael F. Chiang

    Objective To improve clinic efficiency through development of an ophthalmology scheduling template developed using simulation models and electronic health record (EHR) data. Design We created a computer simulation model of one pediatric ophthalmologist’s clinic utilizing EHR timestamp data, which was used to develop a scheduling template based on appointment length (“short”, “medium”, or “long”). We assessed its impact on clinic efficiency after implementation in the practices of five different pediatric ophthalmologists. Subjects Participants, and/or Controls: We observed and timed patient appointments in-person (n=120) and collected EHR timestamps for two years of appointments (n=650). We calculated efficiency measures for 172 clinic sessions pre-implementation vs. 119 clinic sessions post-implementation. Methods Intervention, or Testing: We validated clinic workflow timings calculated from EHR timestamps and the simulation models based on them with observed timings. From simulation tests, we developed a new scheduling template and evaluated it with efficiency metrics pre- vs. post-implementation. Main Outcome Measures Measurements of clinical efficiency (mean clinic volume, patient wait time, exam time, and clinic length). Results Mean physician exam time calculated from EHR timestamps was 13.8 ± 8.2 minutes, and was not statistically different from mean physician exam time from in-person observation (13.3 ± 7.3 minutes) (p=0.7), suggesting that EHR timestamps are accurate. Mean patient wait time for the simulation model (31.2 ± 10.9 minutes) was not statistically different from the observed mean patient wait times ( 32.6 ± 25.3 minutes) (p = 0.9), suggesting that simulation models are accurate. After implementation of the new scheduling template, all five pediatric ophthalmologists showed statistically-significant improvements in clinic volume (mean increase of 1-3 patients/session, p≤0.05 for 2, p≤0.008 for 3), while four of five had improvements in mean patient wait time (average improvements of 3–4 minutes/patient, statistically-significant for 2 providers, p≤0.008). All of the ophthalmologists’ exam times remained the same pre- and post-implementation. Conclusions and Relevance: Simulation models based on “big data” from EHRs can test clinic changes before real-life implementation. A scheduling template using predicted appointment length improves clinic efficiency and may generalize to other clinics. EHRs have potential to become tools for supporting clinic operations improvement.

    更新日期:2018-10-10
  • Increased High Density Lipoprotein-levels associated with Age-related Macular degeneration. Evidence from the EYE-RISK and E3 Consortia
    Ophthalmology (IF 7.479) Pub Date : 2018-10-10
    J.M. Colijn, A.I den Hollander, A. Demirkan, A. Cougnard-Grégoire, T. Verzijden, E. Kersten, M.A. Meester, B.M.J. Merle, G. Papageorgiou, S. Ahmad, M.T. Mulder, M.A. Costa, P. Benlian, G. Bertelsen, A. Bron, B. Claes, C. Creuzot-Garcher, M.G. Erke, C.C.W. Klaver

    Purpose Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design (Pooled) analysis of cross-sectional data. Participants 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. Main Outcome Measures early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

    更新日期:2018-10-10
  • Intralesional Macular Atrophy in Anti–Vascular Endothelial Growth Factor Therapy for Age-Related Macular Degeneration in the IVAN Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-10-06
    Clare Bailey, Lauren J. Scott, Chris A. Rogers, Barnaby C. Reeves, Barbra Hamill, Tunde Peto, Usha Chakravarthy, Simon P. Harding,
    更新日期:2018-10-08
  • Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-10-04
    , Emily Y. Chew, Traci E. Clemons, Glenn J. Jaffe, Charles A. Johnson, Sina Farsiu, Eleonora M. Lad, Robyn Guymer, Philip Rosenfeld, Jean-Pierre Hubschman, Ian Constable, Henry Wiley, Lawrence J. Singerman, Mark Gillies, Grant Comer, Barbara Blodi, Dean Eliott, Jiong Yan, Martin Friedlander

    Purpose To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF) on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. Design Randomized sham-controlled clinical trial Participants 99 study eyes of 67 eligible participants were enrolled. Methods Single-masked randomized clinical trial of 24 months duration conducted May 2014 to April 2017 in eleven clinical centers of retinal specialists in United States and Australia. Participants were randomized 1:1 surgical implant of intravitreal sustained delivery of human ciliary neurotrophic factor (CNTF) vs. sham procedure. Main outcome measures The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral domain optical coherence tomography (SD-OCT) images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. Results Among the 67 participants who were randomized (mean age, 62 ± 8.9 years, 41 (61%) women, 58 (86%) white), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes, the difference in mean area of photoreceptor loss was 0.05 ± 0.03 mm2 (p = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were highly correlated with the changes in the area of photoreceptor loss (r = 0.86, p < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than the treated group (decrease of 15.81±8.93 dB [p=0.07]). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated eyes (p = 0.02). Serious adverse ocular effects were found in 2/51 (4%) of the sham group and 2/48 (4%) in the treated group. Conclusions In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

    更新日期:2018-10-04
  • Risk of Systemic Adverse Events Associated with Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema in Routine Clinical Practice
    Ophthalmology (IF 7.479) Pub Date : 2018-10-04
    Maya H. Maloney, Stephanie R. Schilz, Jeph Herrin, Lindsey R. Sangaralingham, Nilay D. Shah, Andrew J. Barkmeier

    Purpose Intravitreal anti-VEGF pharmacotherapy has become standard of care for the management of diabetic macular edema (DME). The systemic safety profile of this treatment in routine clinical practice remains incompletely understood. We used a large claims database to investigate the risk of systemic adverse events (SAEs) in patients receiving anti-VEGF for DME, compared to controls treated with macular laser photocoagulation or intravitreal corticosteroid. Design Retrospective cohort study Subjects Using a large U.S. insurance database, we identified privately insured and Medicare Advantage patients aged ≥18 years treated with anti-VEGF for DME between 1/1/2006 and 12/31/2015, along with control patients receiving macular laser or corticosteroid. We included patients with one year of medical coverage prior to initial DME treatment. Methods We assessed associations between treatment modalities and predefined systemic outcomes using Cox proportional hazards regression. We performed two separate comparisons, one between anti-VEGF and macular laser and one between anti-VEGF and corticosteroid. We used inverse propensity score weighting for the first comparison to account for treatment selection bias. For the second, we used 2:1 propensity score matching on demographics, year, and baseline comorbidities because of the smaller number of corticosteroid-treated patients. Main Outcome Measures Risk of cerebrovascular disease, myocardial infarction, major bleeding, and all-cause hospitalization occurring within six months of initial DME treatment as hazard ratios (HR) with 95% confidence intervals Results 23,348 patients receiving treatment for DME met inclusion criteria: 13,365 received macular laser, 9,219 received intravitreal anti-VEGF, and 764 received intravitreal corticosteroid as initial treatment. Anti-VEGF pharmacotherapy was not associated with an increased hazard of cerebrovascular disease (HR 0.96 [95% CI, 0.65-1.41], p=0.83), major bleeding (HR 1.23 [95% CI, 0.76-1.99], p=0.41), or myocardial infarction (HR 1.03 [95% CI, 0.73-1.44], p=0.88) when compared to macular laser for DME; however, there was an increased hazard of post-treatment all-cause hospital admission (HR 1.17 [95% CI, 1.05-1.30], p=0.01). The rates of all primary SAE outcomes were similar following treatment with anti-VEGF versus corticosteroid (p>0.05 for all). Conclusion We identified no increased risk of cerebrovascular disease, myocardial infarction, or major bleeding within six months following intravitreal anti-VEGF pharmacotherapy for the treatment of DME in routine clinical practice. A potential difference in all-cause hospitalization may merit further investigation.

    更新日期:2018-10-04
  • Cost-Effectiveness Analysis of Descemet Membrane Endothelial Keratoplasty Compared to Descemet Stripping Endothelial Keratoplasty in the United States of America
    Ophthalmology (IF 7.479) Pub Date : 2018-09-28
    Allister Gibbons, Ella H. Leung, Sonia H. Yoo

    Purpose To determine the cost-effectiveness of Descemet Membrane Endothelial Keratoplasty (DMEK) compared to Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) in the United States (U.S.) Setting Surgical center in the U.S. Design Cost-effectiveness analysis. Subjects Binocular adult patient undergoing endothelial keratoplasty. Methods: Patients A base case of a 70-year-old male undergoing his first endothelial keratoplasty for bilateral Fuchs’ endothelial dystrophy. Intervention The cost-effectiveness of DMEK was compared to DSAEK over a 15-year time horizon. The incidences and costs of complications were derived from PubMed English literature searches, Medicare reimbursements, and average wholesale prices. All costs were discounted 3% per annum and adjusted for inflation to 2018 U.S. dollars. Uncertainty was evaluated using deterministic and probabilistic sensitivity analyses (PSA). Main Outcome Measure Incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR), measured in cost per quality-adjusted-life-years (QALY). Results Performing a DMEK instead of a DSAEK generated an extra 0.4 QALYs over a 15-year period. From a societal and third-party payer perspective, DMEK was cost-saving when compared to DSAEK in improving visual acuity in the base case. PSA with variations in the costs and re-bubble rates revealed that DMEK was cost-saving compared to DSAEK in 38% of iterations and was within a societal willingness-to-pay threshold of $50,000 in 98% of models. Conclusions From the societal and third-party payer perspectives in the U.S., DMEK generated greater utilities and was less costly than DSAEK. Therefore, DMEK was the dominant procedure and was cost-saving with respect to DSAEK. The economic model was robust based on sensitivity analyses.

    更新日期:2018-09-29
  • Are patient self-reported outcome measures (PROMs) sensitive enough to be used as endpoints in clinical trials? Evidence from the United Kingdom Glaucoma Treatment Study
    Ophthalmology (IF 7.479) Pub Date : 2018-09-28
    Lee Jones, David F. Garway-Heath, Augusto Azuara-Blanco, David P. Crabb,

    Purpose The UK Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. We now test the hypothesis that responses on patient reported outcome measures (PROMs – secondary outcome measure) differ between patients receiving a topical prostaglandin analogue (Latanoprost) or placebo eye drops in UKGTS. Design Multi-centre, randomised, triple-masked, placebo-controlled trial. Participants Newly diagnosed glaucoma patients recruited into the UKGTS with baseline and exit PROM data (n= 182 and n=168 patients from the treatment and placebo group, respectively). Methods The UKGTS was a multi-centre, randomised, triple-masked, placebo-controlled trial, where patients with newly diagnosed open angle glaucoma were allocated to receive Latanoprost (treatment) or placebo (trial registration number: ISRCTN96423140); the observation period was 24-months. Patients completed general health PROMs (EQ-5D and SF-36) and PROMs specific to glaucoma (GQL-15 and GAL-9) at baseline and at exit from the trial. Percentage change between baseline and exit measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n=272) and those with glaucomatous progression (n=78), as determined by visual field change (primary outcome), were assessed. Main Outcome Measure PROMs on health-related and vision-related quality of life. Results Average percentage change on PROMs was similar for patients in both arms of the trial with no statistically significant differences between treatment and placebo groups (EQ-5D, p = 0.98; EQ-5D VAS, p = 0.88; SF-36, p = 0.94, GQL-15, p = 0.66; GAL-9, p = 0.87). There were statistically significant differences between stable and progressing patients, as determined by visual fields, on glaucoma-specific PROMs (GQL-15, p = 0.02; GAL-9, p = 0.02) but not on general health PROMs (EQ-5D, p = 0.62; EQ-5D VAS, p = 0.23; SF-36, p = 0.65) Conclusions Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo group in the UKGTS. PROMs, specifically those used in the UKGTS, may not be sensitive enough to be used as a primary endpoint in clinical trials when participants have newly diagnosed early stage glaucoma.

    更新日期:2018-09-29
  • SLT Versus ALT in Glaucoma Patients Treated Previously with 360-degree SLT:A Randomized, Single-Blind, Equivalence Clinical Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-09-29
    Cindy Hutnik, Cindy, Andrew Crichton, Bryce Ford, Marcelo Nicolela, Lesya Shuba, Catherine Birt, Enitan Sogbesan, Karim Damji, Michael Dorey, Hady Saheb, Neil Klar, Hui Guo, William Hodge

    Objective The effectiveness of selective laser trabeculoplasty (SLT) was compared to argon laser trabeculoplasty (ALT) in a randomized clinical trial for patients with medically uncontrolled open angle glaucoma who have previously received 360 degree SLT. Design An active equivalence parallel armed randomized control trial. Participants Patients with open angle glaucoma including pigmentary dispersion syndrome and pseudoexfoliation syndrome were enrolled into the study from seven different sites across Canada. Intervention One setting of 180 degrees of either SLT or ALT was assigned randomly and applied to each participant. Main outcome measures The change in intraocular pressure from baseline to 12 months was compared between the two groups. Results A total of 132 patients were recruited, two of which dropped out early in the study leaving 130 patients who completed the study as per protocol. For those, the study’s primary outcome was calculated. The IOP change at one year in comparison to baseline for SLT vs ALT was found to be different by 0.33 mmHg among the two groups (3.16 for SLT and 2.83 for ALT) and was not statistically significant (p=0.71) Further analysis though showed that SLT had a significantly lower IOP reduction at early time points: 1 week and 1 month, but this effect was lost by 3 months. Corresponding to this finding was the strong trend for ALT to fail more quickly than SLT.. Although repeatable, the first repeat SLT reduced IOP to only about half compared to initial SLT treatment. Conclusion The comparison at 12 months following the laser therapy showed that both modalities lowered the IOP with approximately 3 mm Hg yet essentially all of the time-to-failure analyses favored SLT over ALT. The repeat SLT effect was found to be half of the initial treatment.

    更新日期:2018-09-29
  • Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration
    Ophthalmology (IF 7.479) Pub Date : 2018-09-29
    Katherine G. Chen, Jason A. Alvarez, Mohammad Yazdanie, Chandana Papudesu, Wai T. Wong, Henry E. Wiley, Emily Y. Chew, Frederick L. Ferris, Catherine A. Cukras

    Purpose To investigate the natural history of dark adaptation (DA) function as measured by the change in rod intercept time (RIT) over four years and to correlate RIT change with age-related macular degeneration (AMD) severity. Design Longitudinal, single-center, observational study. Participants 77 participants ≥ 50 years of age with a range of AMD severities. Methods Participants each contributing a single study eye to the analysis were assigned into person-based AMD severity groups based on fundus characteristics (drusen, pigmentary changes, late AMD, and subretinal drusenoid deposits (SDD)). DA function was assessed in study eyes at baseline, 3, 6, 12, 18, 24, 36, and 48 months. Mean change in DA function over time was calculated using the slope of linear regression fits of longitudinal RIT data. Patient-reported responses on a low luminance questionnaire (LLQ) were obtained at baseline and yearly. Nonparametric statistical testing was performed on all comparisons. Main Outcome Measure Rod intercept time (RIT), defined as the time taken following a photobleach for visual sensitivity to recover detection of a 5 x 10-3 cd/m2 stimulus (a decrease of 3 log units), was monitored in study eyes over four years, and the mean rate of change was computed. Results Longitudinal analysis of 65 study eyes followed on the standard testing protocol (mean age, 71±9.3 years; 49% female) revealed that higher rates of RIT prolongation were correlated with AMD severity group assignment at baseline (p=0.026) and with severity group assignments at year 4 (p=0.0011). Study eyes that developed SDD during follow-up demonstrated higher rates of RIT prolongation relative to those that did not (p<0.0001). Overall, higher rates of RIT prolongation were significantly correlated with greater 4-year decreases in LLQ scores (total mean score, p=0.0032). Conclusion Longitudinal decline in DA function, which correlated with patient-reported functional deficits, was accelerated in eyes with greater AMD severity and especially in eyes with SDD both at baseline and at 4 years. RIT prolongation as a measure of changing DA function may be a functional outcome measure in AMD clinical studies.

    更新日期:2018-09-29
  • Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-09-27
    , , Jennifer E. Thorne, Elizabeth A. Sugar, Janet T. Holbrook, Alyce E. Burke, Michael M. Altaweel, Albert T. Vitale, Nisha R. Acharya, John H. Kempen, Douglas A. Jabs

    Purpose To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI). Design Multicenter, randomized clinical trial. Participants Patients with uveitic ME. Methods Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes. Main Outcome Measures The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks. Results All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65–0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56–0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71–1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91–3.65 and HR, 2.52; 95% CI, 1.29–4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups. Conclusions Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.

    更新日期:2018-09-28
  • Sub-Threshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-09-20
    Robyn H. Guymer, Zhichao Wu, Lauren AB. Hodgson, Emily Caruso, Kate H. Brassington, Nicole Tindill, Khin Zaw Aung, Myra B. McGuinness, Erica L. Fletcher, Fred K. Chen, Usha Chakravarthy, Jennifer J. Arnold, Wilson J. Heriot, Shane R. Durkin, Jia Jia Lek, Colin A. Harper, Sanjeewa S. Wickremasinghe, Sukhpal S. Sandhu, Chi D. Luu

    Purpose There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Sub-threshold nanosecond laser (SNL) treatment has been shown in preclinical studies and a pilot study in intermediate AMD (iAMD) to reverse the signs of AMD without causing damage to the overlying retina, thus demonstrating promise as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. Design The Laser intervention in Early stages of Age-related macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial conducted from 2012-2015. Participants 292 participants with bilateral large drusen and without optical coherence tomography signs of atrophy. Interventions Participants were randomly assigned to receive SNL or sham treatment to the study eye at six-monthly intervals. Main Outcomes and Measures The primary efficacy outcome was the time to develop late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. Results Overall, progression to late AMD was not significantly slowed with SNL compared to sham treatment (adjusted hazard ratio [HR] 0·61, 95% CI 0·33–1·14; p=0·122). However, a post-hoc analysis showed that progression was slowed for the 222 (76·0%) participants without coexistent reticular pseudodrusen (RPD) at baseline (adjusted HR 0·23, 95% CI 0·09–0·59; p=0·002), whilst an increased progression rate (adjusted HR 2·56, 95% CI 0·80–8.18; p=0·112) was observed for the 70 (24·0%) participants with RPD with SNL treatment (adjusted interaction p=0·002). Differences between the groups in serious adverse events were not significant. Conclusions In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RTTM laser, but they should not be extrapolated to other short pulse lasers.

    更新日期:2018-09-20
  • Long-term Regular Use of Low-dose Aspirin and Neovascular Age-related Macular Degeneration: National Sample Cohort 2010–2015
    Ophthalmology (IF 7.479) Pub Date : 2018-09-18
    Tyler Hyungtaek Rim, Tae Keun Yoo, Jiyong Kwak, Jihei Sara Lee, Seo Hee Kim, Dong Wook Kim, Sung Soo Kim

    Purpose The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration is controversial. This study was undertaken to estimate the risk of neovascular age-related macular degeneration with long-term regular use of low-dose aspirin. Design Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea. Participants Nonregular aspirin users and regular aspirin users under national health insurance, aged ≥45 years, who were followed from 2010 through 2015, were identified. Methods Incidence per 10,000 person-years for neovascular age-related macular degeneration was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of ≤100 mg aspirin with ≥1044 days-prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score-adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482,613); propensity score-matched analysis in a matched cohort (n = 74,196); and maximally adjusted analysis in the unmatched whole cohort (n = 482,613). Main Outcome Measures Incidence of newly developed neovascular age-related macular degeneration using the registration code for intractable disease under national health insurance. Results Incidence of neovascular age-related macular degeneration was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users, per 10,000 person-years in the unmatched whole cohort. However, propensity score-adjusted analyses revealed no association between aspirin use and neovascular age-related macular degeneration (adjusted hazard ratio, 0.98; 95% confidence interval, 0.73–1.30). Similarly, propensity score-matched analyses showed no association; incidences of neovascular age-related macular degeneration were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude hazard ratio, 0.94; 95% confidence interval, 0.70–1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted hazard ratio, 0.95; 95% confidence interval, 0.71–1.28). Conclusions We found no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular age-related macular degeneration. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular age-related macular degeneration.

    更新日期:2018-09-19
  • Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in High Myopia: A Prospective, Observational Study
    Ophthalmology (IF 7.479) Pub Date : 2018-09-05
    Min-Woo Lee, Ju-mi Kim, Yong-Il Shin, Young-Joon Jo, Jung-Yeul Kim

    Purpose To determine longitudinal change of peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with high myopia without ophthalmic disease. Design Prospective observational study. Participants Participants were divided into 2 groups: a high myopia group (80 eyes) that included eyes with an axial length ≥26.0 mm and a control group (80 eyes) that included eyes with a spherical equivalent (SE) between +3.0 and −6.0 diopters (D). Both groups were further divided into age subgroups by decade: 20s, 30s, 40s, and 50s. Each subgroup included 20 eyes. Methods After the initial visit, pRNFL thickness measurements were performed 2 times more with at least 1-year intervals between examinations using spectral-domain OCT. The mean pRNFL thickness was fitted with linear mixed models. Main Outcome Measures The pRNFL thickness and rate of pRNFL thickness reduction. Results The mean patient age and thickness of the pRNFL at the first visit were 39.5±12.5 years and 90.16±9.06 μm, and 41.5±12.2 years and 96.80±9.50 μm in the high myopia and control groups, respectively. The high myopia group showed a significant reduction in mean pRNFL thickness between the first and second visits, and between the second and third visits (P < 0.001 and P = 0.002, respectively). For individuals aged 50 to 59 years, the reduction rate was −1.69 and −0.63 μm/year in the high myopia and control groups, respectively; the interaction between group and duration was significant (P = 0.014). The reduction rate in individuals aged 40 to 49 years was −1.70 and −0.48 μm/year in the 2 groups, respectively; the interaction was also significant (P = 0.031). Among those aged 30 to 39 years and 20 to 29 years, no such significant interactions were observed (−0.95 vs. −0.57 μm/year, P = 0.086 and −0.31 vs. −0.19 μm/year, P = 0.858, respectively). Conclusions Highly myopic eyes had a significantly greater decrease in pRNFL over 2 years than normal eyes. In addition, the reduction rate of pRNFL thickness was greater in older patients with high myopia, whereas similar values were shown in normal controls except individuals aged 20 to 29 years.

    更新日期:2018-09-05
  • A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus Unilateral Recess-Resect for Basic-Type Intermittent Exotropia
    Ophthalmology (IF 7.479) Pub Date : 2018-09-03
    Sean P. Donahue,

    Purpose To compare long-term outcomes after bilateral lateral rectus recession (BLRc) or unilateral recess-resect (R&R) for primary treatment of childhood intermittent exotropia (IXT). Design Multicenter randomized clinical trial Participants 197 children, age 3 to <11 years, with basic-type IXT, largest deviation by prism and alternate cover test at any distance of 15-40Δ, and near stereoacuity of at least 400 arc-seconds Methods Random assignment to BLRc or R&R. Masked examinations were conducted every 6 months postoperatively for 3 years. Main Outcome Measure The proportion of participants who met suboptimal surgical outcome by 3 years, defined as: 1) exotropia ≥10Δ at distance or near using simultaneous prism and cover test (SPCT), or 2) constant esotropia ≥6Δ at distance or near using SPCT, or 3) loss of ≥2 octaves stereoacuity from baseline, at ANY masked examination; or 4) reoperation without meeting any of these criteria. Results The cumulative probability of suboptimal surgical outcome by 3 years was 46% (43/101) in the BLRc group versus 37% (33/96) in the R&R group (treatment-group difference of BLRc minus R&R = 9%; 95% CI = -6% to 23%). Reoperation by 3 years occurred in 9 (10%) participants in the BLRc group (8 of 9 met suboptimal surgical outcome criteria), and in 4 (5%) participants in the R&R group (3 of 4 met suboptimal surgical outcome criteria) (treatment-group difference of BLRc minus R&R = 5%; 95% CI = -2% to 13%). Among participants who completed the 3-year visit, 29% (25 of 86) in the BLRc group and 17% (13 of 77) in the R&R group underwent reoperation or met suboptimal surgical outcome criteria at the 3-year visit (treatment-group difference of BLRc minus R&R = 12% favoring R&R; 95% CI = -1% to 25%). Conclusions We did not find a statistically significant difference in suboptimal surgical outcome by 3 years between children with IXT treated with BLRc compared with R&R. Based on these findings, we are unable to recommend one surgical approach over the other for childhood IXT.

    更新日期:2018-09-04
  • Macular Morphology and Visual Acuity in Year Five of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT)
    Ophthalmology (IF 7.479) Pub Date : 2018-09-03
    Glenn J. Jaffe, Gui-Shuang Ying, Cynthia A. Toth, Ebenezer Daniel, Juan E. Grunwald, Daniel F. Martin, Maureen G. Maguire,

    Objective To evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT). Design Cohort study within a randomized clinical trial. Participants Participants in CATT. Methods Eyes with AMD-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists’ discretion thereafter. Main Outcome Measures VA; thickness and morphological features on optical coherence tomography; lesion size and foveal composition on fundus photography and fluorescein angiography. Results VA and image gradings were available for 523 of 914 (57%) participants alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had sub-retinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (SD) foveal center thickness (μm) was 148 (99) for retina, 5 (21) for SRF, 125 (107) for subretinal tissue complex, 11 (33) for SHRM, and 103 (95) for RPE+RPE elevation. SHRM, thinner retina, greater CNV lesion area and foveal center pathology (all p<0.001) and IRF (p<0.05), were independently associated with worse VA. Adjusted mean VA letters was 62 for no pathology in the foveal center, 61 for CNV, fluid, or hemorrhage, 65 for non-geographic atrophy (GA), 64 for non-fibrotic scar, 53 for GA, and 56 for fibrotic scar. Incidence or worsening of eight pathological features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF, retinal thinning, CNV lesion area, and GA area) between years 2 and 5 were independently associated with greater loss of VA from year 2 to 5, and VA loss from baseline to year 5 . Conclusions Associations between VA and morphologic features previously identified through year 1 were maintained or strengthened at year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning, development or worsening of foveal GA, and increased lesion size, are important contributers to the VA decline from year 2 to 5. A significant need to develop therapies to address these adverse pathological features remains.

    更新日期:2018-09-04
  • Outbreak of Adenovirus in a Neonatal Intensive Care Unit
    Ophthalmology (IF 7.479) Pub Date : 2018-09-01
    Julia S. Sammons, Erin H. Graf, Sara Townsend, Cindy L. Hoegg, Sarah A. Smathers, Susan E. Coffin, Katie Williams, Stephanie L. Mitchell, Ursula Nawab, David Munson, Graham Quinn, Gil Binenbaum

    Purpose Outbreaks of adenovirus in neonatal intensive care units (NICUs) can lead to widespread transmission and serious adverse outcomes. We describe the investigation, response, and successful containment of an adenovirus outbreak in a NICU associated with contaminated handheld ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. Design Epidemiologic outbreak investigation. Participants A total of 23 hospitalized neonates, as well as NICU staff and parents of affected infants. Main Outcome Measures Routine surveillance identified an adenovirus outbreak in a level IV NICU in August 2016. Epidemiologic investigation followed, including chart review, staff interviews, and observations. Cases were defined as hospital-acquired adenovirus identified from any clinical specimen (NICU patient or employee) or compatible illness in a family member. Real-time polymerase chain reaction (PCR) and partial- and whole-genome sequencing assays were used for testing of clinical and environmental specimens. Results We identified 23 primary neonatal cases and 9 secondary cases (6 employees and 3 parents). All neonatal case-patients had respiratory symptoms. Of these, 5 developed pneumonia and 12 required increased respiratory support. Less than half (48%) had ocular symptoms. All neonatal case-patients (100%) had undergone a recent ophthalmologic examination, and 54% of neonates undergoing examinations developed adenovirus infection. All affected employees and parents had direct contact with infected neonates. Observations revealed inconsistent disinfection of bedside ophthalmologic equipment and limited glove use. Sampling of 2 handheld lenses and 2 indirect ophthalmoscopes revealed adenovirus serotype 3 DNA on each device. Sequence analysis of 16 neonatal cases, 2 employees, and 2 lenses showed that cases and equipment shared 100% identity across the entire adenovirus genome. Infection control interventions included strict hand hygiene, including glove use; isolation precautions; enhanced cleaning of lenses and ophthalmoscopes between all examinations; and staff furlough. We identified no cases of secondary transmission among neonates. Conclusions Adenovirus outbreaks can result from use of contaminated ophthalmologic equipment. Even equipment that does not directly contact patients can facilitate indirect transmission. Patient-to-patient transmission can be prevented with strict infection control measures and equipment cleaning. Ophthalmologists performing inpatient examinations should take measures to avoid adenoviral spread from contaminated handheld equipment.

    更新日期:2018-09-03
  • Childhood lensectomy is associated with static and dynamic reduction in Schlemm canal size: a biomechanical hypothesis of post-lensectomy glaucoma
    Ophthalmology (IF 7.479) Pub Date : 2018-08-30
    Moritz C. Daniel, Adam M. Dubis, Maria Theodorou, Ana Quartilho, Gillian Adams, John Brookes, Maria Papadopoulos, Peng T. Khaw, Annegret H. Dahlmann-Noor

    Objective To compare Schlemm canal (SC) and trabecular meshwork (TM) in children with healthy eyes and those with and without glaucoma after lensectomy. Design Cross-sectional observational study Participants Fifty children age 4 to 16 years with healthy eyes and 48 children post lensectomy (124 healthy and 72 post-lensectomy eyes) Methods /Interventions: Anterior segment optical coherence tomography (AS-OCT, Tomey Casia) of the nasal iridocorneal angle, at two levels of accommodative effort (2.5D, 15D). For each parameter and state of accommodation, a random-effects model was fitted to estimate differences between healthy eyes and eyes with history of lensectomy. Main Outcome Measures Dimensions of SC and TM; conventional AS-OCT irido-corneal angle (ICA) measurements Results The horizontal diameter of SC and its cross-sectional area (SC-CSA) are significantly smaller in post-lensectomy than in healthy eyes. Accommodative effort increases SC size in healthy, but not in post-lensectomy eyes. Conclusions Lensectomy is associated with a reduction in SC size and a loss of physiological SC dilatation during accommodative effort, which may reflect a reduction in outflow facility and contribute to the development of post-lensectomy glaucoma.

    更新日期:2018-08-30
  • Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch’s Membrane
    Ophthalmology (IF 7.479) Pub Date : 2018-04-26
    Jordi Corominas, Johanna M. Colijn, Maartje J. Geerlings, Marc Pauper, Bjorn Bakker, Najaf Amin, Laura Lores Motta, Eveline Kersten, Alejandro Garanto, Joost A.M. Verlouw, Jeroen G.J. van Rooij, Robert Kraaij, Paulus T.V.M. de Jong, Albert Hofman, Johannes R. Vingerling, Tina Schick, Sascha Fauser, Eiko K. de Jong, Anneke I. den Hollander

    PurposeGenome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants.DesignGenome-wide case-control association study of WES data.ParticipantsOne thousand one hundred twenty-five AMD patients and 1361 control participants.MethodsA single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes.Main Outcome MeasuresGenetic variants associated with AMD.ResultsWe detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10–5). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch’s membrane.ConclusionsThis study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch’s membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch’s membrane, contributing to the accumulation of drusen and the development of AMD.

    更新日期:2018-07-14
  • Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE
    Ophthalmology (IF 7.479) Pub Date : 2018-05-08
    Rahul K. Reddy, Dante J. Pieramici, Shamika Gune, Avanti Ghanekar, Na Lu, Carlos Quezada-Ruiz, Caroline R. Baumal

    PurposeTo determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients’ potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months.DesignPost hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330).ParticipantsStudy eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline.MethodsTo measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest.Main Outcome MeasuresBaseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24.ResultsBaseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm.ConclusionsDespite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy.

    更新日期:2018-05-08
  • Phenotypic Characteristics of a French Cohort of Patients with X-Linked Retinoschisis
    Ophthalmology (IF 7.479) Pub Date : 2018-05-05
    Raphaëlle Orès, Saddek Mohand-Said, Claire-Marie Dhaenens, Aline Antonio, Christina Zeitz, Edouard Augstburger, Camille Andrieu, José-Alain Sahel, Isabelle Audo

    PurposeTo analyze the retinal structure in patients with X-linked retinoschisis (XLRS) using spectral-domain OCT and to correlate the morphologic findings with visual acuity, electroretinographic results, and patient age.DesignRetrospective, observational study.ParticipantsData from 52 consecutive male patients with molecularly confirmed XLRS were collected retrospectively.MethodsComplete clinical evaluation included best-corrected visual acuity, full-field electroretinography, fundus photography, spectral-domain OCT, and fundus autofluorescence. Spectral-domain OCT images were analyzed to determine full thickness of the retina and tomographic structural changes.Main Outcome MeasuresRelationships between age, OCT, and visual acuity were assessed.ResultsOne hundred four eyes of 52 patients were included. The mean age at inclusion was 24±15 years (range, 3–57 years). The best-corrected visual acuity ranged from no light perception to 0.1 logarithm of the minimum angle of resolution (mean, 0.6±0.38 logarithm of the minimum angle of resolution). Macular schisis was found in 88% of eyes and macular atrophy was found in 11% of eyes, whereas peripheral schisis was present in 30% of eyes. A spoke-wheel pattern of high and low intensity was the most frequently observed fundus autofluorescence abnormality (51/94 eyes [54%]). The b-to-a amplitude ratio on bright-flash dark-adapted electroretinography was reduced significantly in 45 of 64 eyes (70%). Spectral-domain OCT was available for 97 eyes and showed foveoschisis in 76 of 97 eyes (78%), parafoveal schisis in 10 of 97 eyes (10%), and foveal atrophy in 11 of 97 eyes (11%). Mean central macular thickness (CMT) was of 373.6±140 μm. Cystoid changes were localized mainly in the inner nuclear layer (85/97 eyes [88%]). Qualitative defects in photoreceptor structures were found in most eyes (79/97 eyes [81%]), and the most frequent abnormality was an interruption of the photoreceptor cell outer segment tips (79/79 eyes [100%]). Older age correlated well with lower CMT (correlation coefficient [CC], –0.44; P < 0.001) and with lower photoreceptor outer segment (PROS) length (CC, –0.42; P < 0.001). Lower visual acuity correlated strongly with lower PROS length (CC, –0.53; P < 0.001).ConclusionsThis study underlined the wide variety of clinical features of XLRS. It highlighted the correlation between visual acuity, patient age, and OCT features, emphasizing the relevance of the latter as potential outcome measure in clinical trials.

    更新日期:2018-05-06
  • Five-Year Graft Survival of Descemet Membrane Endothelial Keratoplasty (EK) versus Descemet Stripping EK and the Effect of Donor Sex Matching
    Ophthalmology (IF 7.479) Pub Date : 2018-05-03
    David A. Price, Meagan Kelley, Francis W. Price Jr., Marianne O. Price

    PurposeTo determine whether the reduced risk of immunologic rejection with Descemet membrane endothelial keratoplasty (DMEK) results in a 5-year survival advantage relative to Descemet stripping endothelial keratoplasty (DSEK) and to determine whether matching the donor and recipient sex affects the rejection episode and graft survival rates.DesignRetrospective cohort study.ParticipantsPatients with Fuchs’ endothelial corneal dystrophy treated with DSEK or DMEK.MethodsThis study reviewed 2017 consecutive cases (1312 DSEK and 705 DMEK) performed by 13 surgeons between 2003 and 2012 and included the surgeons’ first cases. Survival rates were calculated by Kaplan–Meier analysis.Main Outcome MeasuresImmunologic rejection episodes, graft failure or replacement for any reason, and endothelial cell loss.ResultsThe 5-year rejection episode rate was lower with DMEK (2.6% vs. 7.9% with DSEK, relative risk, 0.29; 95% confidence interval, 0.16–0.53) despite early reduction of topical corticosteroids in 25% of the DMEK cases. African Americans (n = 46) had a higher risk of rejection episodes than other races (relative risk, 4.4; 95% confidence interval, 2.0–9.6). The cumulative 5-year survival rate was 93% with DSEK and DMEK (P = 0.86). Forty-four DMEK and 69 DSEK grafts failed or were replaced within 5 years, but only 1 DMEK and 4 DSEK failures followed a rejection episode. Rejection episodes increased endothelial cell loss (P = 0.004) but were not a significant risk factor for graft failure within 5 years (P = 0.90). The mean 5-year endothelial cell loss was similar between DMEK (48%±19%) and DSEK (47%±19%) (P = 0.22). Graft rejection episode and survival rates were not significantly influenced by whether the sex of the donor matched that of the recipient (rejection episodes: P = 0.07 for female recipients and P = 0.33 for male recipients; graft survival: P = 0.67 for female recipients and P = 0.17 for male recipients).ConclusionsFive-year graft survival was similar between DMEK and DSEK. Although DMEK had a significantly lower risk of immunologic rejection, rejection episodes rarely resulted in graft failure within 5 years with either procedure. Sex matching the donor and recipient provided no survival advantage with DSEK or DMEK.

    更新日期:2018-05-03
  • Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration : A Randomized Clinical Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-04-30
    Philip J. Rosenfeld, Pravin U. Dugel, Frank G. Holz, Jeffrey S. Heier, Joel A. Pearlman, Roger L. Novack, Karl G. Csaky, John M. Koester, Jeffrey K. Gregory, Ryo Kubota

    PurposeTo determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment.DesignMulticenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial.ParticipantsPatients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2 were enrolled.MethodsSubjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25.Main Outcome MeasuresThe primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point.ResultsOf 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%).ConclusionsEmixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug’s mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.

    更新日期:2018-04-30
  • Ultrawide-Field OCT to Investigate Relationships between Myopic Macular Retinoschisis and Posterior Staphyloma
    Ophthalmology (IF 7.479) Pub Date : 2018-04-30
    Kosei Shinohara, Noriko Tanaka, Jost B. Jonas, Noriaki Shimada, Muka Moriyama, Takeshi Yoshida, Kyoko Ohno-Matsui

    PurposeTo investigate the relationships between myopic macular retinoschisis (MRS) and posterior staphylomas and to reveal the characteristics of other retinal lesions associated with MRS.DesignRetrospective, observational case series.ParticipantsSeven hundred twenty-nine eyes of 420 patients with high myopia, which was defined as myopic refractive error of more than –8.0 diopters or an axial length longer than 26.5 mm.MethodsHighly myopic eyes were examined by ultrawide-field (UWF) swept-source (SS) OCT with scan width of up to 23 mm and scan depth of 5 mm. The OCT features of MRS and posterior staphylomas and their spatial relationship were examined in UWF SS OCT images.Main Outcome MeasuresAssociations between MRS and staphylomas.ResultsIn 729 eyes with mean axial length of 30.2±2.1 mm, posterior staphyloma was detected in 482 eyes (66.1%) and MRS was detected in 136 eyes (18.7%). All 136 eyes with an MRS showed outer retinoschisis, and 40 eyes (29.4%) also showed inner retinoschisis. Posterior staphyloma was detected significantly more frequently in eyes with MRS (117/136 [86.0%]) than in eyes without MRS (365/593 [61.6%]; P < 0.001). In all eyes with both staphyloma and outer retinoschisis, the area of the outer retinoschisis was restricted to the area within the staphyloma. In 1 of the 19 eyes with outer retinoschisis but without staphyloma, the outer retinoschisis extended beyond the range of the scanned fundus area. Among the 40 eyes with inner retinoschisis, the inner retinoschisis was located within the region of the outer retinoschisis in 39 eyes (97.5%). In all eyes with inner retinoschisis, retinal lesions causing an inward-directed tractional force were found within the area of the inner retinoschisis.ConclusionsIn highly myopic eyes, the sites of the MRS and staphylomas were spatially related to each other. Posterior-directed force in association with staphylomas, and an inward-directed force resulting from epiretinal membranes or vitreoretinal attachments, may act as causative factors for MRS. However, the exact mechanisms related to the development of an MRS are probably diverse and complex.

    更新日期:2018-04-30
  • Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis
    Ophthalmology (IF 7.479) Pub Date : 2018-04-30
    Jiraporn Jitprapaikulsan, John J. Chen, Eoin P. Flanagan, W. Oliver Tobin, Jim P. Fryer, Brian G. Weinshenker, Andrew McKeon, Vanda A. Lennon, Jacqueline A. Leavitt, Jan-Mendelt Tillema, Claudia Lucchinetti, B. Mark Keegan, Orhun Kantarci, Cheryl Khanna, Sarah M. Jenkins, Grant M. Spears, Jessica Sagan, Sean J. Pittock

    PurposeTo determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment.DesignCross-sectional cohort study.ParticipantsThe study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000–March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing.MethodsSerum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG.Main Outcomes MeasuresAquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes.ResultsAmong 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1−positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG−positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG−positive patients, between counting fingers and hand movements in MOG IgG1−positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG−positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1−positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG−positive patients, 22% of idiopathic patients, 12% of MOG IgG1−positive patients, and 8% of MS patients were estimated to have severe visual loss.ConclusionsGlial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.

    更新日期:2018-04-30
  • Management of Acute Retinal Ischemia : Follow the Guidelines!
    Ophthalmology (IF 7.479) Pub Date : 2018-04-30
    Valérie Biousse, Fadi Nahab, Nancy J. Newman

    Acute retinal arterial ischemia, including vascular transient monocular vision loss (TMVL) and branch (BRAO) and central retinal arterial occlusions (CRAO), are ocular and systemic emergencies requiring immediate diagnosis and treatment. Guidelines recommend the combination of urgent brain magnetic resonance imaging with diffusion-weighted imaging, vascular imaging, and clinical assessment to identify TMVL, BRAO, and CRAO patients at highest risk for recurrent stroke, facilitating early preventive treatments to reduce the risk of subsequent stroke and cardiovascular events. Because the risk of stroke is maximum within the first few days after the onset of visual loss, prompt diagnosis and triage are mandatory. Eye care professionals must make a rapid and accurate diagnosis and recognize the need for timely expert intervention by immediately referring patients with acute retinal arterial ischemia to specialized stroke centers without attempting to perform any further testing themselves. The development of local networks prompting collaboration among optometrists, ophthalmologists, and stroke neurologists should facilitate such evaluations, whether in a rapid-access transient ischemic attack clinic, in an emergency department–observation unit, or with hospitalization, depending on local resources.

    更新日期:2018-04-30
  • Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population
    Ophthalmology (IF 7.479) Pub Date : 2018-04-30

    PurposeTo investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population.DesignCross-sectional meta-analysis.ParticipantsA total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3–82.1±4.2 years) of the European Eye Epidemiology (E3) consortium.MethodsWe examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis.Main Outcome MeasuresDeterminants of pRNFLT.ResultsMean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = –0.38 μm/year; 95% confidence interval [CI], –0.57 to –0.18), higher intraocular pressure (IOP) (β = –0.36 μm/mmHg; 95% CI, –0.56 to –0.15), visual impairment (β = –5.50 μm; 95% CI, –9.37 to –1.64), and history of systemic hypertension (β = –0.54 μm; 95% CI, –1.01 to –0.07) and stroke (β = –1.94 μm; 95% CI, –3.17 to –0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = –3.11 μm; 95% CI, –6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19–1.59) and smoking (β = 1.53 μm; 95% CI, 1.00–2.06 for current smokers compared with never-smokers).ConclusionsIn addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.

    更新日期:2018-04-30
  • Patterns of Progressive Ganglion Cell–Inner Plexiform Layer Thinning in Glaucoma Detected by OCT
    Ophthalmology (IF 7.479) Pub Date : 2018-04-25
    Joong Won Shin, Kyung Rim Sung, Sun-Won Park

    PurposeTo investigate the spatial characteristics and patterns of progressive macular ganglion cell–inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA).DesignLongitudinal, retrospective, observational study.ParticipantsTwo hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2–8.1 years) were included.MethodsMacular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index.Main Outcome MeasuresSpatial characteristics and patterns of progressive GCIPL thinning.ResultsSeventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°–339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression.ConclusionsThe use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

    更新日期:2018-04-26
  • Steroids versus No Steroids in Nonarteritic Anterior Ischemic Optic Neuropathy : A Randomized Controlled Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-04-25
    Rohit Saxena, Digvijay Singh, Medha Sharma, Mathew James, Pradeep Sharma, Vimla Menon

    PurposeTo examine the role of oral steroid therapy in the treatment of nondiabetic cases of acute nonarteritic anterior ischemic optic neuropathy (NAAION).DesignRandomized double-blind clinical trial.ParticipantsThirty-eight patients with acute nondiabetic NAAION divided into 2 arms of 19 patients each. One arm constituted the cases and the other constituted the controls.MethodsCases received oral steroid therapy and were designated the steroid group, whereas controls received placebo and were designated the nonsteroid group. Best-corrected visual acuity (BCVA), visual evoked response (VER), and OCT were performed at baseline, 1 month, 3 months, and 6 months after recruitment into the trial.Main Outcome MeasuresBest-corrected visual acuity, VER, and retinal nerve fiber layer changes on OCT.ResultsBoth groups showed significant improvement in BCVA, VER latency, and resolution of disc edema on OCT parameters over 6 months. Final outcome showed no statistically significant difference with regard to visual acuity, although VER was better in the steroid group (P = 0.011). Best-corrected visual acuity, VER amplitude, and VER latency (P = 0.02, P = 0.02, and P = 0.04, respectively) showed a greater percentage improvement in the steroid group, which also saw a faster resolution of disc edema on OCT (1-month follow-up).ConclusionsOral steroids in acute NAAION did not improve the visual acuity significantly at 6 months. However, they improved resolution of disc edema significantly and enabled a greater improvement in VER parameters. This subtle benefit of oral steroids in NAAION is clinically unimportant and does not provide support for its use.

    更新日期:2018-04-26
  • Effects of Prolonged Reading on Dry Eye
    Ophthalmology (IF 7.479) Pub Date : 2018-04-25
    Sezen Karakus, Devika Agrawal, Holly B. Hindman, Claudia Henrich, Pradeep Y. Ramulu, Esen K. Akpek

    PurposeTo demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters.DesignProspective, observational clinical study.ParticipantsA total of 177 patients with dry eye and 34 normal controls aged 50 years and older.MethodsAfter evaluating symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, the following tests were performed in consecutive order: automated noninvasive tear break-up time (TBUT), surface asymmetry and regularity indices, Schirmer’s testing without anesthesia, corneal staining using fluorescein, and conjunctival staining using lissamine green. The participants were then asked to read a 30-minute validated passage silently. The tests were repeated after the reading task.Main Outcome MeasuresChanges in tear film and ocular surface parameters after reading.ResultsAll parameters, with the exception of surface asymmetry index, worsened after the reading task in patients with dry eye and in controls. The worsening reached a statistical significance for corneal and conjunctival staining in the dry eye group (P < 0.001) and for corneal staining in the control group (P < 0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P < 0.001). Among postreading measurements, baseline OSDI scores correlated with TBUT (r = −0.15, P = 0.03) in addition to corneal and conjunctival staining (r = 0.25, P < 0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer’s test correlated significantly with their respective baseline values (r = −0.61, P < 0.001 and r = −0.44, P < 0.001), indicating that the more unstable the tear film and the lower the aqueous tear secretion, the worse they became after the prolonged reading task. Worsening in corneal staining directly correlated with the baseline conjunctival staining (r = 0.17, P = 0.02) and surface regularity index (r = 0.21, P = 0.01).ConclusionsEvaluating tear film and ocular surface parameters at rest may miss clinical findings brought about by common everyday tasks such as reading, leading to discordance between patient-reported symptoms and clinician-observed signs. Quantifying dry eye after visually straining activities such as prolonged silent reading may help better understand patient symptomatology.

    更新日期:2018-04-26
  • Long-Term Metastatic Risk after Biopsy of Posterior Uveal Melanoma
    Ophthalmology (IF 7.479) Pub Date : 2018-04-25
    Mette Bagger, Isabel Smidt-Nielsen, Mette K. Andersen, Peter K. Jensen, Steffen Heegaard, Klaus K. Andersen, Søren Friis, Jens F. Kiilgaard

    PurposeBiopsy of posterior uveal melanoma continues to be intensely debated in terms of the clinical benefits and safety profile. Although several studies have reported a low frequency of ocular complications after tumor biopsy, the potential long-term risk of iatrogenic dissemination remains unresolved. The purpose of this study was to assess the risk of metastatic disease after biopsy of posterior uveal melanoma.DesignRetrospective nationwide cohort study linking clinical and histopathologic records to pathology, cancer, and mortality registries.ParticipantsAll patients with posterior uveal melanoma treated in Denmark between January 1985 and December 2016.MethodsFor each patient, we recorded detailed information on age, gender, tumor characteristics, and diagnostic and therapeutic measures, including tumor biopsy, if any, and the primary treating hospital. Absolute risk of melanoma-specific death was presented by cumulative incidence curves that accounted for competing risks. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and melanoma-specific mortality of patients who underwent biopsy during primary treatment compared with nonbiopsied patients through November 1, 2017. Fine and Gray risk regression was used as a sensitivity analysis to evaluate the impact of competing risks.Main Outcome MeasuresAll-cause and melanoma-specific mortality.ResultsAmong 1637 patients, 567 (35%) underwent biopsy during primary treatment. At diagnosis, biopsied patients exhibited better prognostic characteristics, including smaller tumor size (P < 0.001) and younger age (P < 0.001), than nonbiopsied patients. In the adjusted analyses, we observed no apparent differences in all-cause mortality (HR, 1.07; 95% CI, 0.89–1.26; P = 0.47) or melanoma-specific mortality (HR, 1.11; 95% CI, 0.89–1.39; P = 0.35) among biopsied patients compared with nonbiopsied patients.ConclusionsAll-cause and melanoma-specific mortality after primary treatment were similar among biopsied and nonbiopsied patients with posterior uveal melanoma. Our findings do not support an increased metastatic risk after intraocular tumor biopsy.

    更新日期:2018-04-26
  • A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography
    Ophthalmology (IF 7.479) Pub Date : 2018-04-10
    Felix Grassmann, Judith Mengelkamp, Caroline Brandl, Sebastian Harsch, Martina E. Zimmermann, Birgit Linkohr, Annette Peters, Iris M. Heid, Christoph Palm, Bernhard H.F. Weber

    PurposeAge-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm.DesignAlgorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study.ParticipantsWe included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study.MethodsWe defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study.Main Outcome Measuresκ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification.ResultsA network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%–92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly.ConclusionsOur deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age.

    更新日期:2018-04-10
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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