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  • Paracentral Acute Middle Maculopathy following Vitrectomy for Proliferative Diabetic Retinopathy
    Ophthalmology (IF 7.479) Pub Date : 2018-08-17
    Hiroshi Nakashima, Yasuaki Iwama, Kensuke Tanioka, Kazuyuki Emi

    PurposeTo report the incidence of, risk factors for, and characteristics of paracentral acute middle maculopathy (PAMM) after 25-gauge pars plana vitrectomy for proliferative diabetic retinopathy (PDR).DesignRetrospective, consecutive, interventional case series.ParticipantsFive hundred thirty eyes of 427 patients who underwent primary vitrectomy for PDR from 2013 through 2016.MethodsThe patients underwent measurement of best-corrected visual acuity (BCVA), fundus photography, and OCT before and within 2 weeks after vitrectomy. A generalized linear mixed-effects model was used to evaluate risk factors for development of PAMM.Main Outcome MeasuresThe incidence, associated risk factors, and clinical characteristics of PAMM following vitrectomy, including the change in BCVA in eyes with PAMM and the distribution of PAMM as determined by en face OCT.ResultsFour hundred ninety-six eyes of 395 patients who met the eligibility criteria were evaluated. The incidence of PAMM was 3.8% (15/395) for patients and 3.6% (18/496) for eyes. Multivariate analysis showed the significant risk factors for PAMM development to be younger age (mean age, 49 years in patients and 59 years in control participants; odds ratio [OR] 0.94; 95% confidence interval [CI], 0.89–0.99; P = 0.021) and female gender (66.7% of patients and 31.3% of control participants; OR, 4.48; 95% CI, 1.57–12.6; P = 0.005). The PAMM was distributed on either side of the causative arterioles. In 14 of the 18 eyes (78%), PAMM was located within a 3-mm diameter of the fovea. In 10 eyes (56%), PAMM measured 1 disc diameter or more, and in 5 eyes (28%), PAMM measured one third disc diameter less. No emboli were found in any eyes; however, multiple segmental arterial constrictions were confirmed during vitrectomy in 1 eye. The BCVA decreased more than 2 lines in 2 eyes (5%).ConclusionsParacentral acute middle maculopathy can develop after pars plana vitrectomy for PDR, especially in patients who are younger and female. Impaired blood flow in arterioles, which leads to tissue hypoxia, was associated with development of PAMM.

    更新日期:2018-08-17
  • Mediterranean diet and incidence of advanced AMD: The EYE-RISK CONSORTIUM
    Ophthalmology (IF 7.479) Pub Date : 2018-08-13
    Bénédicte MJ. Merle, Johanna M. Colijn, Audrey Cougnard-Grégoire, Alexandra P.M. de Koning-Backus, Marie-Noëlle Delyfer, Jessica C. Kiefte-de Jong, Magda Meester-Smoor, Catherine Féart, Timo Verzijden, Cécilia Samieri, Oscar H. Franco, Jean-François Korobelnik, Caroline C.W. Klaver, Cécile Delcourt,

    Objective To investigate associations of adherence to the Mediterranean diet (MeDi) with incidence of advanced AMD (the symptomatic form of AMD) in two European population-based prospective cohorts. Design Prospective cohorts: the Rotterdam Study I (RS-I) and the Alienor Study. Participants 4 446 participants aged ≥55 years from RS-I (The Netherlands) and 550 French adults aged 73 years or older from Alienor Study with complete ophthalmologic and dietary data were included in the present study. Methods Examinations were performed approximately every 5 years over a 21-year period (1990 to 2011) in RS-I and every 2 years over a 4-year period (2006 to 2012) in Alienor Study. Adherence to the MeDi was evaluated using a 9 component score based on intake of vegetables, fruits, legumes, cereals, fish, meat, dairy products, alcohol and the monounsaturated-to-saturated fatty acids ratio. Associations of incidence of AMD with MeDi were estimated using multivariate Cox proportional Hazard models. Main outcomes measures Incidence of advanced AMD based on retinal fundus photographs. Results Among the 4 996 included participants, 155 developed advanced incident AMD (117 from RS-I and 38 from Alienor Study). The mean follow-up time was 9.9 years (range 0.6 to 21.7) in RS-I and 4.1 years (range 2.5 to 5.0) in Alienor Study. Pooling data for both RS-I and Alienor study, participants with a high (6-9) MeDi score had a significantly reduced risk for incident advanced AMD compared to participants with a low (0-3) MeDi score in the fully-adjusted Cox model (HR, 0.59 [95% CI, 0.37-0.95], p for trend=0.04). Conclusion Pooling data from RS-I and Alienor, higher adherence to the MeDi was associated with a 41% reduced risk of incident advanced AMD. These findings support the role of a diet rich in healthful nutrient-rich foods such as fruits, vegetables, legumes and fish in the prevention of AMD.

    更新日期:2018-08-14
  • A comparison between the Compass fundus perimeter and the Humphrey Field Analyzer
    Ophthalmology (IF 7.479) Pub Date : 2018-08-14
    Giovanni Montesano, Susan R. Bryan, David P. Crabb, Paolo Fogagnolo, Francesco Oddone, Allison M. McKendrick, Andrew Turpin, Paolo Lanzetta, Andrea Perdicchi, Chris A. Johnson, David F. Garway-Heath, Paolo Brusini, Luca M. Rossetti

    Purpose To evaluate relative diagnostic precision and test retest variability of two devices, the Compass (CMP, CenterVue, Italy) fundus perimeter and the Humphrey Field Analyzer (HFA, Zeiss, Dublin), in detecting glaucomatous optic neuropathy (GON). Design Multicentre cross-sectional case–control study. Subjects We sequentially enrolled 499 glaucoma patients and 444 normal subjects to analyse relative precision. A separate group of 44 glaucoma patients and 54 normal subjects was analysed to assess test – retest variability. Methods One eye of the recruited subjects was tested with the index tests: HFA (SITA Standard strategy) and CMP (ZEST strategy) with a 24-2 grid. The reference test for GON was specialist evaluation of fundus photographs or OCT, independent of the visual field. For both devices, linear regression was used to calculate the sensitivity decrease with age in the normal group to compute pointwise Total Deviation (TD) values and Mean Deviation (MD). We derived 5% and 1% pointwise normative limits. MD and the total number of TD values below 5% (TD 5%) or 1% (TD 1%) limits per field were used as classifiers. Main Outcome Measures We used partial Receiver Operating Characteristic (ROC) curves and partial Area Under the Curve (pAUC) to compare the diagnostic precision of the devices. Pointwise Mean Absolute Deviation (MAD) and Bland Altman plots for the mean sensitivity (MS) were computed to assess test- retest variability. Results Retinal sensitivity was generally lower with CMP, with an average mean difference of 1.85 ± 0.06 dB (Mean ± Standard Error, p < 0.001) in healthy subjects and 1.46 ± 0.05 dB (Mean ± Standard Error, p < 0.001) in patients with glaucoma. Both devices showed similar discriminative power. The MD metric had marginally better discrimination with CMP (pAUC difference ± Standard Error, 0.019 ± 0.009, p = 0.035). The 95% limits of agreement for the MS were reduced by 13% in CMP compared to HFA in glaucoma subjects, and by 49% in normal subjects. MAD was very similar, with no significant differences. Conclusions Relative diagnostic precision of the two devices is equivalent. Test-retest variability of mean sensitivity for CMP was better than for HFA.

    更新日期:2018-08-14
  • Spectral Domain-Optical Coherence Tomography Measurements in Alzheimer’s Disease: A Systematic Review and Meta-analysis
    Ophthalmology (IF 7.479) Pub Date : 2018-08-13
    Victor T.T. Chan, Zihan Sun, Shumin Tang, Li Jia Chen, Adrian Wong, Clement C. Tham, Tien Y. Wong, Christopher Chen, M. Kamran Ikram, Heather E. Whitson, Eleonora M. Lad, Vincent Mok, Carol Y. Cheung

    TopicOptical coherence tomography (OCT) is a non-invasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral domain-OCT (SD-OCT) measurements with Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD-OCT measurements in AD and MCI.Clinical RelevanceCurrent methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD-OCT, which are non-invasive, technically simple and inexpensive, are potential biomarkers of AD.MethodsWe conducted a literature search in PubMed and EMBASE to identify studies published before 31 December 2017 which assessed the associations between AD, MCI and measurements of SD-OCT: ganglion cell-inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume and choroidal thickness, in addition to retinal nerve fibre layer (RNFL) and macular thickness. We used a random-effect model to examine these relationships. We also conducted meta-regression, and assessed heterogeneity, publication bias and study quality.ResultsWe identified 30 eligible studies, involving 1257 AD subjects, 305 MCI subjects and 1460 controls; all of which were cross-sectional studies. In terms of the macular structure, AD subjects had significant differences in GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence interval [CI], -0.80 to -0.11; I2= 71%), GCC thickness (SMD, -0.84; 95% CI, -1.10 to -0.57; I2 = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I2 = 80%) and macular thickness of all inner and outer sectors (SMD ranged -0.52 to -0.74; all p<0.001) when compared to controls. Peripapillary RNFL thickness (SMD, -0.67; 95% CI, -0.95 to -0.38; I2 = 89%) and choroidal thickness (SMD ranged -0.88 to -1.03; all p<0.001) were also thinner in AD.ConclusionOur results confirmed the associations between retinal measurements of SD-OCT, and AD, highlighting the potential utility of SD-OCT measurements as biomarkers of AD.

    更新日期:2018-08-13
  • Association between Rates of Visual Field Progression and Intraocular Pressure Measurements Obtained by Different Tonometers
    Ophthalmology (IF 7.479) Pub Date : 2018-08-13
    Bianca N. Susanna, Nara G. Ogata, Fábio B. Daga, Carolina N. Susanna, Alberto Diniz-Filho, Felipe A. Medeiros

    PurposeTo investigate the associations between intraocular pressure (IOP) measurements obtained by different tonometric methods and rates of visual field loss in a cohort of glaucoma patients followed over time.DesignProspective observational cohort study.ParticipantsThis study included 213 eyes of 125 glaucomatous patients that were followed for an average of 2.4 ± 0.6 years.MethodsAt each visit, IOP measurements were obtained using Goldmann applanation tonometer (GAT), Ocular Response Analyzer (ORA) corneal-compensated IOP (IOPcc), and ICare rebound tonometer (RBT). Rates of visual field loss were assessed by Standard Automated Perimetry (SAP) mean deviation (MD). Linear mixed models were used to investigate the relationship between mean IOP by each tonometer and rates of visual field loss over time, while adjusting for age, race, central corneal thickness, and corneal hysteresis (CH).Main Outcome MeasuresStrength of associations (R2) between IOP measurements from each tonometer and rates of SAP MD change over time.ResultsAverage values for mean IOP over time measured by GAT, ORA and RBT were 14.4 ± 3.3, 15.2 ± 4.2, and 13.4 ± 4.2 mmHg, respectively. Mean IOPcc had the strongest relationship with SAP MD loss over time (R2=24.5%), and was significantly different from the models using mean GAT IOP (R2=11.1%; 95% confidence interval (CI) of the difference: 6.6% to 19.6%) and mean RBT IOP (R2=5.8%; 95% CI of the difference: 11.1% to 25.0%).ConclusionsMean ORA IOPcc was more predictive of rates of visual field loss than mean IOP obtained by GAT or RBT. By correcting for corneal-induced artifacts, IOPcc measurements may present significant advantages for predicting clinically relevant outcomes in glaucoma patients.

    更新日期:2018-08-13
  • Donor, Recipient and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study
    Ophthalmology (IF 7.479) Pub Date : 2018-08-09
    Mark A. Terry, Anthony J. Aldave, Loretta B. Szczotka-Flynn, Wendi Liang, Allison R. Ayala, Maureen G. Maguire, Christopher Croasdale, Yassine J. Daoud, Steven P. Dunn, Caroline K. Hoover, Marian S. Macsai, Thomas F. Mauger, Sudeep Pramanik, George OD. Rosenwasser, Jennifer Rose-Nussbaumer, R. Doyle Stulting, Alan Sugar, Elmer Y. Tu, Jonathan H. Lass

    Purpose To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). Design Cohort study within a multi-center, double-masked, randomized clinical trial. Participants 1,090 individuals (1,330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic/aphakic corneal edema (PACE, 6% of eyes). Methods Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0-7 days (N=675) or 8-14 days (N=655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as re-graft for any reason, a graft that failed to clear by 8 weeks post-operatively, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was further classified as primary or early donor failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and {99% confidence intervals} for graft failure. Main Outcome Measure Graft success at 3 years Results 1251/1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR: 2.35 {1.03, 5.33}) and operative complications (RR: 4.21 {1.42, 12.47}) were associated with increased risk for primary/early failure. Preoperative diagnosis of PACE (RR: 3.59 {1.05, 12.24}) was associated with increased risk for late failure by 3 years postoperatively compared to Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR: 1.19 {0.91, 1.56} per decade), preoperative donor endothelial cell density (RR: 1.10 {0.74, 1.63} per 500 cells), graft diameter (RR: 1.22 {0.39, 3.76} per mm) and injector use for graft insertion (RR: 0.92 {0.40, 2.10}). Conclusions DSAEK success in the early and entire postoperative period is more likely when the donor did not have diabetes and without operative complications, and in the long term postoperative period in recipients with Fuchs dystrophy compared to PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success following DSAEK warrant further study.

    更新日期:2018-08-10
  • Patient-Reported Visual Disability in Fuchs’ Endothelial Corneal Dystrophy Measured by the Visual Function and Corneal Health Status Instrument
    Ophthalmology (IF 7.479) Pub Date : 2018-08-10
    Katrin Wacker, Keith H. Baratz, William M. Bourne, Sanjay V. Patel

    Purpose Measuring patient-reported visual disability in Fuchs’ endothelial corneal dystrophy (FECD) may be helpful in determining when to intervene and for understanding the outcomes of intervention. In this study, we aimed to validate a new patient-reported visual disability questionnaire, the Visual Function and Corneal Health Status (V-FUCHS) instrument, in FECD before and after endothelial keratoplasty (EK). Design Cross-sectional study with instrument readministration at 6 weeks. Participants Patients with a range of severity of FECD, including after EK, and patients with healthy corneas. Methods The V-FUCHS instrument was developed based on patient interviews, expert consultations, and pretesting. Psychometric methods of classic test theory were applied to estimate reliability and validity, including testing V-FUCHS against Catquest-9SF, a cataract-specific visual disability questionnaire. Ordered polytomous Rasch-based partial credit models and item response theory diagnostics were used to define the response patterns. Main Outcome Measures Reliability (primary) and validity (secondary). Results The final instrument was completed by 65% of patients with a range of severity of FECD (n = 41), after undergoing EK for FECD (n = 70), and with healthy corneas (n = 28). Participants were phakic or pseudophakic. Exploratory factor analysis among FECD and patients who underwent EK showed 2 independent factors of visual disability: 7 items related to visual acuity and 8 items related to glare or diurnal variation. Retest reliability was substantial (intraclass correlation coefficient, ≥0.8, both factors). Among all patients, the visual acuity factor was correlated with Catquest-9SF scores (r = 0.65; P < 0.001; n = 96). The glare or diurnal variation factor increased with FECD severity (P < 0.001, n = 69) and was higher in FECD than healthy participants (P < 0.001). Diagnostics revealed that both factors were well calibrated and met Rasch model expectations. Conclusions The V-FUCHS instrument is valid and reliable for assessing visual disability in FECD. The instrument allows for standardized, comprehensive, and rapid assessment of disease-specific visual disability and may be useful in clinical practice and research as a patient-reported outcome measure.

    更新日期:2018-08-10
  • The phenotypic spectrum of albinism
    Ophthalmology (IF 7.479) Pub Date : 2018-08-08
    Charlotte C. Kruijt, Gerard C. de Wit, Arthur A. Bergen, Ralph J. Florijn, Nicoline E. Schalij-Delfos, Maria M. van Genderen

    Purpose To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity, and to define diagnostic criteria for the Caucasian population. We also estimated the prevalence of albinism in the Netherlands. Design Retrospective cohort study. Subjects We investigated the phenotype of 522 albinism patients from the databases of Bartiméus (452 patients), Leiden University Medical Center (44 patients) and the Academic Medical Center Amsterdam (26 patients). Methods We collected clinical, genetic and electrophysiological data of albinism patients. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia. Main Outcome Measures Visual acuity (VA), nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia and misrouting. Results In 7.7% (40/521) nystagmus was absent, iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496) had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia and in 16.1% (49/304) misrouting was not established. The VA varied from -0.1 to 1.3 logMAR. The foveal hypoplasia grading correlated best with the VA (r=0.69, p < 0.001), while iris translucency, fundus pigmentation and misrouting did not predict the VA significantly. We estimated a prevalence of albinism in the Netherlands of at least 1: 12 000. Conclusions None of the characteristics of albinism were consistently present in our cohort. To be able to distinguish albinism from other conditions with similar ocular features, especially in northern and western European countries, we propose major and minor clinical criteria. Major criteria would be 1) foveal hypoplasia grade 2 or more, 2) misrouting, and 3) ocular hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or more. Minor criteria would be 1) nystagmus, 2) hypopigmentation of skin and hair, 3) grade 1 fundus hypopigmentation, and 4) foveal hypoplasia grade 1. We propose that three major criteria, or two major and two minor criteria are necessary for the diagnosis. In the presence of a molecular diagnosis, one major criterion or two minor criteria will be sufficient.

    更新日期:2018-08-08
  • Rationale and Application of the Protocol S Anti-Vascular Endothelial Growth Factor Algorithm for Proliferative Diabetic Retinopathy
    Ophthalmology (IF 7.479) Pub Date : 2018-08-07
    Jennifer K. Sun, Adam R. Glassman, Wesley T. Beaulieu, Cynthia R. Stockdale, Neil M. Bressler, Christina Flaxel, Jeffrey G. Gross, Michel Shami, Lee M. Jampol

    Objective Present rationale, guidelines, and results of ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S. Design Post hoc analyses from a randomized clinical trial. Participants Three hundred and five participants with 394 study eyes having PDR without prior PRP. Intervention Post hoc analyses from a randomized clinical trial of 0.5-mg intravitreous ranibizumab versus panretinal photocoagulation (PRP) for PDR. Eyes assigned to ranibizumab (N=191) received monthly injections for 6 months unless resolution after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. PRP could be initiated for failure or futility criteria. Main outcome measures Neovascularization status through 2 years. Results At 1 month, 19% (35 of 188) of ranibizumab-assigned eyes had complete neovascularization resolution (including fibrous proliferans) and an additional 60% (113) were improved. At 6 months, 52% (80 of 153) had neovascularization resolution, 3% (4) were still improving, 37% (56) were stable, and 8% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1-7; N = 73) versus 7 (4-11; N = 67) (P<.001). Injections were deferred in 68 of 73 eyes (93%) meeting sustained stability at least once during the study; 62% (42 of 68) resumed injections within 16 weeks after deferral. At 2 years, 43% (66 of 154) had neovascularization resolution, 5% (7) were improved, 23% (36) were stable, and 27% (42) had worsened since the last visit. Only 3 eyes met criteria for failure or futility through 2 years. Conclusions The DRCR Network treatment algorithm for PDR can provide excellent clinical outcomes through two years for patients initiating anti-VEGF therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by consideration of the relative advantages of each therapeutic modality and anticipated patient compliance with follow-up and treatment recommendations.

    更新日期:2018-08-07
  • Relationship between retinal thickness profiles and visual outcomes in young adults born extremely preterm: The EPICure@19 Study
    Ophthalmology (IF 7.479) Pub Date : 2018-08-06
    Siva Balasubramanian, Joanne Beckmann, Hemal Mehta, SriniVas R. Sadda, Karntida Chanwimol, Marco Nassisi, Irena Tsui, Neil Marlow, Saurabh Jain

    Purpose To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). Design Prospective observational study with 19 years follow-up Participants A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period and 13% (30) had neonatal cryotherapy or laser ablation for ROP. Methods Subjects underwent eye examinations including best corrected visual acuity (BCVA) and Heidelberg Spectralis macular spectral domain optical coherence tomography (SD-OCT) imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. Main outcome measure Correlation between retinal sublayer thickness and BCVA. Results Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, p < 0.001) but outer retinal layer thickness was not (r = -0.01, p = 0.80). Multivariate regression indicated ganglion cell layer thickness was a significant independent predictor of BCVA. Conclusions Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

    更新日期:2018-08-06
  • Oral Memantine for the Treatment of Glaucoma
    Ophthalmology (IF 7.479) Pub Date : 2018-08-03
    Robert N. Weinreb, Jeffrey M. Liebmann, George A. Cioffi, Ivan Goldberg, James D. Brandt, Chris A. Johnson, Linda M. Zangwill, Susan Schneider, Hanh Badger, Marina Bejanian
    更新日期:2018-08-03
  • Six-year incidence of and risk factors for cataract surgery in a multi-ethnic Asian population: The Singapore Epidemiology of Eye Diseases Study
    Ophthalmology (IF 7.479) Pub Date : 2018-08-02
    Ava Grace Tan, Annette Kifley, Yih Chung Tham, Yuan Shi, Miao Li Chee, Charumathi Sabanayagam, Nicholas Yi Qiang Tan, Kah Hie Wong, Paul Mitchell, Robert G. Cumming, Tien Yin Wong, Jie Jin Wang, Ching-Yu Cheng

    Purpose To report the 6-year incidence of cataract surgery in an Asian population-based cohort of Malays, Indians and Chinese living in Singapore, and factors associated with having cataract surgery over the follow-up period. Design Population-based, prospective cohort study. Subjects During 2004-2011, 10,033 participants (3,280 Malays, 3,400 Indians and 3,353 Chinese) aged 40+ years participated in the Singapore Epidemiology of Eye Diseases (SEED) Study. Six years later, 6762 participants (78.7% of eligible, including 1901 (72.1% of eligible) Malays, 2200 (75.5% of eligible) Indians and 2661 (87.7% of eligible) Chinese) were re-examined. Methods Detailed eye examinations including slit-lamp biomicroscopy were conducted at both visits. Logistic regression models were used to assess factors associated with cataract surgery after adjusting for age, sex, socioeconomic status and other risk factors. Main outcome measure Incident cataract surgery. Results The 6-year incidence of cataract surgery was 11.0% (9.5%, 12.6% and 11.1% for Malays, Indians and Chinese, respectively), and was strongly age-related (P for trend <.001). After adjustment, baseline factors associated with incident cataract surgery included older age (odds ratio, OR, 1.13 per year increase, 95% confidence interval, CI, 1.11-1.14), diabetes (OR 1.90, 95% CI 1.54-2.33), myopia (OR 1.78, 95% CI 1.44-2.20), and presence of any cataract: nuclear cataract (OR 3.78, 95% CI 2.91-4.89), cortical cataract (OR 3.01, 95% CI 2.45-3.71), posterior subcapsular cataract (OR 5.00, 95% CI 3.91-6.41). The population attributable risk of cataract surgery related to diabetes and myopia were 17.6% and 19.1%, respectively. Conclusions One in ten Malay, Indian and Chinese Singaporeans aged 40 years and above had cataract surgery in at least one eye over 6 years. In Asian populations, diabetes and myopia, two well-known factors associated with cataract prevalence, are significant and potentially modifiable factors associated with the need for cataract surgery.

    更新日期:2018-08-02
  • Outcomes of Eyes Lost to Follow-Up with Proliferative Diabetic Retinopathy that received Panretinal Photocoagulation vs Intravitreal Anti-Vascular Endothelial Growth Factor
    Ophthalmology (IF 7.479) Pub Date : 2018-08-02
    Anthony Obeid, Daniel Su, Samir N. Patel, Joshua H. Uhr, Durga Borkar, Xinxiao Gao, Mitchell S. Fineman, Carl D. Regillo, Joseph I. Maguire, Sunir J. Garg, Jason Hsu

    Purpose To compare anatomic and functional outcomes in eyes with proliferative diabetic retinopathy (PDR) that were lost to follow-up (LTFU) for more than 6 months after treatment with either intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents or panretinal photocoagulation (PRP). Design Retrospective cohort study. Participants Fifty-nine patients who were LTFU immediately after treatment for >6 months between September 2013 and September 2016. Methods Patients with eyes receiving either intravitreal anti-VEGF treatment or PRP with the next follow-up visit occurring > 6 months after treatment were identified. Visual acuity (VA) and anatomic outcomes at the visit before LTFU, the return visit, the 6-month visit after return, the 12-month visit after return, and the final visit were gathered and compared between the two treatment groups. Main Outcomes Measures VA and anatomic outcomes. Results Seventy-six eyes of 59 patients were included in the study of which 30 received IVI with anti-VEGF, and 46 received PRP. In the eyes that received intravitreal anti-VEGF, mean logMAR VA significantly worsened when comparing the visit before LTFU (0.43 [±0.38], Snellen 20/54) to the return visit (0.97 [±0.80], Snellen 20/187, p=0.001) as well as the final visit (0.92 [±0.94], Snellen 20/166, p=0.01). In eyes that received PRP, mean logMAR VA significantly worsened when comparing the visit before LTFU (0.42 [±0.34], Snellen 20/53) to the return visit (0.62 [±0.64], Snellen 20/83, p=0.03). However, no significant difference was observed at the final visit (0.46 [±0.47] Snellen 20/58, p=0.38). There was a significantly greater number of eyes with tractional retinal detachment in the IVI group compared to the PRP group at the return visit (5 vs 0, p=0.008) and the final visit (10 vs 1, p=0.005). There was a significantly greater incidence of neovascularization of the iris in the IVI arm compared to the PRP arm at the final visit (4 vs 0, p=0.02) Conclusion Eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after LTFU compared to eyes that received PRP. Given the potential sequelae of LTFU, the choice of treatment for PDR must be carefully considered.

    更新日期:2018-08-02
  • Safety and Efficacy of Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration
    Ophthalmology (IF 7.479) Pub Date : 2018-08-02
    Sophie J. Bakri, Jennifer E. Thorne, Allen C. Ho, Justis P. Ehlers, Scott D. Schoenberger, Steven Yeh, Stephen J. Kim

    Objective To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (AMD). Methods A literature search of the PubMed and Cochrane Library databases was last conducted in February 2017; there were no date restrictions and the search was limited to studies published in English. The combined searches yielded 191 citations, 28 of which were selected because they were clinical trials and were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous Panel to review in full. The panel methodologist then assigned a level of evidence rating to each study. Results Sixteen of the 28 citations provided level I evidence supporting the use of anti-VEGF agents for neovascular AMD, including intravitreal ranibizumab, aflibercept, and bevacizumab. Eight studies reviewed provided level II evidence and 4 provided level III evidence, but only the level I studies are included in this assessment. There is long-term follow-up data on the efficacy of ranibizumab and bevacizumab (≥5 years), but this is subject to the bias of incomplete follow-up. Conclusions Review of the literature indicates that intravitreal injection of anti-VEGF therapy is safe and effective for neovascular AMD over 2 years, the period for which data is available. Further research is needed to evaluate the long-term safety and comparative efficacy of these agents.

    更新日期:2018-08-02
  • Ophthalmic Technology Assessment: The Use of Beta-Blockers for the Treatment of Periocular Hemangiomas in Infants
    Ophthalmology (IF 7.479) Pub Date : 2018-08-01
    Amy K. Hutchinson, Raymond T. Kraker, Stacy L. Pineles, Deborah K. VanderVeen, Lorri B. Wilson, Jennifer A. Galvin, Scott R. Lambert

    Objective To review the published literature assessing the efficacy of beta-blockers for the treatment of periocular hemangioma in infants. Methods Literature searches were conducted in May 2018 in PubMed with no date restrictions and limited to studies published in English and in the Cochrane Library database without any restrictions. The combined searches yielded 437 citations. Of these,16 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Results None of the 16 studies included in this assessment were rated level I, 3 were rated level II, and 13 were rated level III. The most common treatment regimen was 2 mg/kg daily oral propranolol, but intralesional and topical beta-blockers were also used. Treatment effect was most often measured in terms of reduction in the size of the lesions, which occurred in the majority of patients. Beta-blockers were consistently shown to reduce astigmatism, but this reduction was shown to be statistically significant in only 2 series. The effect of beta-blockers on amblyopia was not adequately documented. Beta-blockers were generally well tolerated and had mild side effects (fatigue, gastrointestinal upset/diarrhea, restlessness/sleep disturbances, minor wheezing, and cold extremities). Complications severe enough to require cessation of treatment occurred in only 2 patients out of a total of 229 who received beta-blockers. Conclusions There is limited evidence to support the safety and efficacy of both topical and systemic beta-blockers to promote regression of periocular hemangiomas. Additional research may confirm the best dosage and route of administration to maximize efficacy in reducing induced astigmatism and amblyopia associated with periocular hemangiomas while minimizing side effects.

    更新日期:2018-08-01
  • Retinal vasculometry associations with cardiometabolic risk factors in the European Prospective Investigation of Cancer Norfolk study
    Ophthalmology (IF 7.479) Pub Date : 2018-08-01
    Christopher G. Owen, Alicja R. Rudnicka, Roshan A. Welikala, M Moazam Fraz, Sarah A. Barman, Robert Luben, Shabina A. Hayat, Kay-Tee Khaw, David P. Strachan, Peter H. Whincup, Paul J. Foster

    Purpose To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. Design Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye study. Participants 7411 participants underwent retinal imaging and clinical assessment. Retinal images were analysed using a fully automated validated computerised system, which provides novel measures of vessel morphometry. Methods Associations between cardiometabolic risk factors, chronic disease and retinal markers were analyzed using multi-level linear regression, adjusted for age, sex and within person clustering, to provide percentage differences in tortuosity and absolute differences in width. Main outcomes measures Retinal arteriolar and venular tortuosity and width. Results 279,802 arterioles, and 285,791 venules from 5947 participants (mean age 67.6 years, SD 7.6, 57% female) were analysed. Increased venular tortuosity was associated with higher BMI (2.5%, 95% CI 1.7,3.3% per 5 kg/m2) and HbA1c (2.2%, 95%CI 1.0,3.5% per %), and with prevalent type 2 diabetes (6.5%, 95%CI 2.8,10.4%); wider venules were associated with older age (2.6μm, 95%CI 2.2,2.9μm per decade), higher triglycerides (0.6μm, 95%CI 0.3,0.9μm per mmol/L), BMI (0.7μm, 95%CI 0.4,1.0 per 5 kg/m2) and HbA1c (0.4μm, 95%CI -0.1,0.9 per %) and being a current smoker (3.0μm, 95%CI 1.7,4.3μm); similarly smoking was also associated with wider arterioles (2.1μm, 95%CI 1.3,2.9μm). Thinner venules were associated with HDL (1.4μm, 95%CI 0.7,2.2 per mmol/L). Arteriolar tortuosity increased with age (5.4%, 95%CI 3.8,7.1% per decade), higher systolic blood pressure (1.2%, 95%CI 0.5,1.9% per 10mmHg), in females (3.8, 95%CI 1.4,6.4%) and with prevalent stroke (8.3%, 95%CI -0.6,18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8μm, 95%CI 0.6,1.0μm per decade), higher systolic blood pressure (0.5μm, 95%CI 0.4,0.6μm per 10mmHg), total cholesterol (0.2μm, 95%CI 0.0,0.3μm per mmol/L) and HDL (1.2μm, 95%CI 0.7,1.6μm per mmol/L). Conclusions Metabolic risk factors show a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlate more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These non-invasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease among apparently healthy individuals.

    更新日期:2018-08-01
  • Progression of Geographic Atrophy in Age-related Macular Degeneration
    Ophthalmology (IF 7.479) Pub Date : 2018-07-27
    Tiarnan D. Keenan, Elvira Agrón, Amitha Domalpally, Traci E. Clemons, Freekje van Asten, Wai T. Wong, Ronald G. Danis, SriniVas Sadda, Philip J. Rosenfeld, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L. Ferris, Emily Y. Chew

    Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P < 0.0001 for interaction in each case) but not with AREDS2 treatment assignment (P = 0.33) or smoking status (P = 0.05). Enlargement was significantly faster with ARMS2 risk (P < 0.0001), C3 non-risk (P = 0.0002), and APOE non-risk (P = 0.001) genotypes. Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

    更新日期:2018-07-27
  • Intravitreal Sirolimus for the Treatment of Noninfectious Uveitis
    Ophthalmology (IF 7.479) Pub Date : 2018-07-27
    Quan Dong Nguyen, Pauline T. Merrill, Yasir J. Sepah, Mohamed A. Ibrahim, Alay Banker, Andrea Leonardi, Michelle Chernock, Sri Mudumba, Diana V. Do

    In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1–3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 μg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 μg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-μg group than in the 44-μg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1–3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 μg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

    更新日期:2018-07-27
  • Differing Structural and Functional Patterns of Optic Nerve Damage in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
    Ophthalmology (IF 7.479) Pub Date : 2018-07-27
    Ting Shen, Yuyi You, Sukanya Arunachalam, Ariadna Fontes, Sidong Liu, Vivek Gupta, John Parratt, Chenyu Wang, Michael Barnett, Joshua Barton, Nitin Chitranshi, Ling Zhu, Clare L. Fraser, Stuart L. Graham, Alexander Klistorner, Con Yiannikas

    Purpose To assess differential patterns of axonal loss and demyelination in the optic nerve in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Design Cross-sectional study. Participants One hundred ninety-two participants, including 136 MS patients (272 eyes), 19 NMOSD patients (38 eyes), and 37 healthy control participants (74 eyes). Methods All participants underwent spectral-domain OCT scans and multifocal visual evoked potential (mfVEP) recordings. High-resolution magnetic resonance imaging (MRI) with the diffusion protocol also was performed in all patients. Main Outcome Measures Ganglion cell–inner plexiform layer (GCIPL) thickness and mfVEP amplitude and latency at 5 eccentricities; global and temporal retinal nerve fiber layer thickness. Results In optic neuritis (ON) eyes, the NMOSD patients had more severe GCIPL loss (P < 0.001) and mfVEP amplitude reduction (P < 0.001) compared with MS patients, whereas in contrast, mfVEP latency delay was more evident in MS patients (P < 0.001). The NMOSD patients showed more morphologic and functional loss at the foveal to parafoveal region, whereas the MS patients showed evenly distributed damage at the macula. Correlation analysis demonstrated a strong structure–function (OCT–mfVEP) association in the NMOSD patients, which was only moderate in the MS patients. In non-ON (NON) eyes, the MS patients showed significantly thinner GCIPL than controls (P < 0.001), whereas no GCIPL loss was observed in NON eyes in NMOSD. In addition, a significant correlation was found between all OCT and mfVEP measures in MS patients, but not in NMOSD patients. MRI demonstrated significant lesional load in the optic radiation in MS compared to NMOSD eyes (P = 0.002), which was related to the above OCT and mfVEP changes in NON eyes. Conclusions Our study demonstrated different patterns of ON damage in NMOSD and MS. In MS, the ON damage was less severe, with demyelination as the main pathologic component, whereas in NMOSD, axonal loss was more severe compared with myelin loss. The disproportional mfVEP amplitude and latency changes suggested predominant axonal damage within the anterior visual pathway as the main clinical feature of NMOSD, in contrast to MS, where demyelination spreads along the entire visual pathway.

    更新日期:2018-07-27
  • Distinguishing Highly Asymmetric Keratoconus Eyes Using Combined Scheimpflug and Spectral Domain OCT Analysis
    Ophthalmology (IF 7.479) Pub Date : 2018-07-25
    Eric S. Hwang, Claudia E. Perez-Straziota, Sang Woo Kim, Marcony R. Santhiago, J. Bradley Randleman

    PurposeTo determine optimal objective, machine-derived variables and variable combinations from Scheimpflug and spectral domain (SD) OCT imaging to distinguish the clinically unaffected eye in patients with asymmetric keratoconus (AKC) from a normal control population.DesignRetrospective case-control study.ParticipantsThirty clinically unaffected eyes with no physical findings on slit-lamp examination, no definitive abnormalities on corneal imaging, and corrected distance acuity of 20/20 or better from 30 patients with highly AKC eyes and 60 eyes from 60 normal control patients who had undergone uneventful LASIK with at least 2 years of stable follow-up (controls).MethodsScheimpflug and SD OCT imaging were obtained in all eyes, and receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity for each machine-derived variable and variable combination.Main Outcome MeasuresDistinguishing AKC eyes from controls as determined by AUC, sensitivity, and specificity.ResultsNo individual machine-derived metric from Scheimpflug or SD OCT technology yielded an AUC higher than 0.75. Combining 5 Scheimpflug metrics (index height decentration [IHD], index vertical asymmetry [IVA], pachymetry apex, inferior-superior value, and Ambrosio’s Relational Thickness Maximum [ARTmax]) yielded the best Scheimpflug results (AUC 0.86, sensitivity 83%, specificity 83%). Combining 11 SD OCT thickness metrics (minimum-median, temporal outer, superior nasal outer, minimum, epithelium minimum-maximum, epithelial standard deviation, superior inner, superior outer, superior temporal outer, superior nasal inner, central) yielded the best SD OCT results (AUC 0.96, sensitivity 89%, specificity 89%). Combining 13 total Scheimpflug/SD OCT metrics yielded the best results overall (AUC 1.0, sensitivity 100%, specificity 100%). The most impactful variables in combined models included epithelial thickness variability and total focal corneal thickness variability from SD OCT and anterior curvature and topometric indices from Scheimpflug technology. No posterior corneal metrics were impactful in modeling.ConclusionsIndividual machine-derived metrics from Scheimpflug and SD OCT imaging poorly distinguished normal eyes from minimally affected eyes from patients with highly AKC. Combined SD OCT metrics performed better than combined Scheimpflug metrics. Combining anterior curvature and asymmetry indices from Scheimpflug with regional total thickness and epithelial thickness variability metrics from SD OCT clearly distinguished the 2 populations. Posterior corneal indices were not useful in distinguishing populations.

    更新日期:2018-07-25
  • Joubert Syndrome: Ophthalmological Findings in Correlation with Genotype and Hepatorenal Disease in 99 Patients Prospectively Evaluated at a Single Center
    Ophthalmology (IF 7.479) Pub Date : 2018-07-25
    Brian P. Brooks, Wadih M. Zein, Amy H. Thompson, Maryam Mokhtarzadeh, Daniel A. Doherty, Melissa Parisi, Ian A. Glass, May C. Malicdan, Thierry Vilboux, Meghana Vemulapalli, James C. Mullikin, William A. Gahl, Meral Gunay-Aygun
    更新日期:2018-07-25
  • Contact Lens Correction of Aphakia in Children
    Ophthalmology (IF 7.479) Pub Date : 2018-04-07
    Scott R. Lambert, Raymond T. Kraker, Stacy L. Pineles, Amy K. Hutchinson, Lorri B. Wilson, Jennifer A. Galvin, Deborah K. VanderVeen

    Purpose To review the published literature to assess the visual outcomes and adverse events associated with the 2 most commonly used contact lenses for treating aphakia in children: silicone elastomer (SE) and rigid gas permeable (RGP). Methods Literature searches were last conducted in January 2018 in the PubMed, Cochrane Library, and ClinicalTrials.gov databases with no date or language restrictions. These combined searches yielded 167 citations, 27 of which were reviewed in full text. Of these, 10 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologist. Results The literature search identified 4 level II studies and 6 level III studies. There were insufficient data to compare visual outcomes for eyes treated using SE lenses versus RGP lenses. Silicone elastomer lenses have the advantage that they can be worn on an extended-wear basis, but they were associated with more adverse events than RGP lenses. These adverse events included microbial keratitis, corneal infiltrates, corneal edema, corneal scars, lenses adhering to the cornea, superficial punctate keratopathy, lid swelling, and conjunctival hyperemia. The lens replacement rate was approximately 50% higher for RGP lenses in the only study that directly compared SE and RGP lenses. Conclusions Limited evidence was found in the literature on this topic. Silicone elastomer and RGP contact lenses were found to be effective for treating aphakia in children. Silicone elastomer lenses are easier to fit and may be worn on an extended-wear basis. Rigid gas permeable lenses must be removed every night and require a more customized fit, but they are associated with fewer adverse events. The choice of which lens a practitioner prescribes should be based on the particular needs of each patient.

    更新日期:2018-07-23
  • Posterior Vitreous Detachment as Observed by Wide-Angle OCT Imaging
    Ophthalmology (IF 7.479) Pub Date : 2018-04-07
    Mayuka Tsukahara, Keiko Mori, Peter L. Gehlbach, Keisuke Mori

    Purpose Posterior vitreous detachment (PVD) plays an important role in vitreoretinal interface disorders. Historically, observations of PVD using OCT have been limited to the macular region. The purpose of this study is to image the wide-angle vitreoretinal interface after PVD in normal subjects using montaged OCT images. Design An observational cross-sectional study. Participants A total of 144 healthy eyes of 98 normal subjects aged 21 to 95 years (51.4±22.0 [mean ± standard deviation]). Methods Montaged images of horizontal and vertical OCT scans through the fovea were obtained in each subject. Main Outcome Measures Montaged OCT images. Results By using wide-angle OCT, we imaged the vitreoretinal interface from the macula to the periphery. PVD was classified into 5 stages: stage 0, no PVD (2 eyes, both aged 21 years); stage 1, peripheral PVD limited to paramacular to peripheral zones (88 eyes, mean age 38.9±16.2 years, mean ± standard deviation); stage 2, perifoveal PVD extending to the periphery (12 eyes, mean age 67.9±8.4 years); stage 3, peripapillary PVD with persistent vitreopapillary adhesion alone (7 eyes, mean age 70.9±11.9 years); stage 4, complete PVD (35 eyes, mean age 75.1±10.1 years). All stage 1 PVDs (100%) were observed in the paramacular to peripheral region where the vitreous gel adheres directly to the cortical vitreous and retinal surface. After progression to stage 2 PVD, the area of PVD extends posteriorly to the perifovea and anteriorly to the periphery. Vitreoschisis was observed in 41.2% at PVD initiation (stage 1a). Conclusions Whereas prior work suggests that PVD originates in the perifoveal region and after the sixth decade, our observations demonstrate that (1) PVD first appears even in the third decade of life and gradually appears more extensively throughout life; (2) more than 40% of eyes without fundus diseases at their PVD initiation are associated with vitreoschisis; and (3) PVD is first noted primarily in the paramacular-peripheral region where vitreous gel adheres to the retinal surface and is noted to be more extensive in older ages to ultimately involve the fovea.

    更新日期:2018-07-23
  • A Database Study of Visual Outcomes and Intraoperative Complications of Postvitrectomy Cataract Surgery
    Ophthalmology (IF 7.479) Pub Date : 2018-07-21
    Mohamed Kamel Soliman, Joshua S. Hardin, Fayez Jawed, Sami H. Uwaydat, Mohammed F. Faramawi, Colin J. Chu, Yit C. Yang, Ahmed B. Sallam

    Purpose To analyze the visual outcomes and rate of intraoperative complications of phacoemulsification surgery after prior pars plana vitrectomy (PPV). Design Retrospective, multicenter database study. Participants Eyes that underwent phacoemulsification between June 2005 and March 2015 at 8 sites in the United Kingdom. Methods Study eyes were classified as vitrectomized (prior PPV group) or nonvitrectomized (reference group) depending on the vitreous state at the time of cataract surgery. Eyes with multiple intraocular surgeries or history of ocular diseases known to cause cataract progression or increased risk of intraoperative complications during phacoemulsification were excluded. Main Outcome Measures Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), rate of intraoperative complications, and time interval to cataract surgery. Results Eyes in the prior PPV group (n = 2221) had worse preoperative logMAR VA (0.96±0.60 vs. 0.62±0.52, P < 0.0001), were from younger patients, and had longer axial lengths than the nonvitrectomized group (n = 136 533). At all postoperative time points measured up to 24 weeks, mean vision was poorer in the prior PPV group (0.41±0.47 vs. 0.17±0.29 at 4–12 weeks, P < 0.0001) and a smaller proportion of eyes achieved postoperative VA ≤0.30 logMAR (Snellen, ≥20/40) (60.8% vs. 86.5% at 4–12 weeks, P < 0.0001). The rate of posterior capsular rupture was not different between the prior PPV (1.5%) and the nonvitrectomized (1.7%) groups, but the incidences of zonular dialysis (1.3% vs. 0.6%) and dropped nuclear fragments (0.6% vs. 0.2%) were higher in the prior PPV group (P < 0.0001). The mean time interval between PPV and cataract surgery was 399 days. Conclusions We found a significant improvement in VA with postvitrectomy cataract surgery. However, compared with eyes without prior PPV, there was a worse mean postoperative vision of 0.2 logMAR units, a higher rate of zonular dialysis and dropped nuclear fragments, and a similar rate of posterior capsule rupture.

    更新日期:2018-07-22
  • Intraocular Foreign Body Trauma in Operation Iraqi Freedom and Operation Enduring Freedom
    Ophthalmology (IF 7.479) Pub Date : 2018-07-20
    Grant A. Justin, Katherine M. Baker, Daniel I. Brooks, Denise S. Ryan, Eric D. Weichel, Marcus H. Colyer

    Purpose We update the incidence of intraocular foreign bodies (IOFB) in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries in Operation Iraqi Freedom and Operation Enduring Freedom. Design This consecutive retrospective case series included 890 eyes of 652 patients. Methods Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were any American soldier or Department of Defense civilian with an IOFB injured in Operation Iraqi Freedom/Operation Enduring Freedom. Closed globe injuries with orbital foreign bodies, injury outside of a combat zone, or non–Department of Defense civilian trauma were the exclusion criteria. Main Outcome Measures Primary outcome measures were final visual outcome and the number, size, and location of IOFBs. Secondary outcome measures included surgical procedures, use of eye protection, associated complications, source of injury and Ocular Trauma Score. Results There were 890 eye injuries in 652 patients evacuated to Walter Reed Army Medical Center between 2001 and 2011. IOFBs were found in 166 eyes of 149 patients (18.6%; 95% confidence interval [CI], 16.2%–21.3%). Most patients had a single IOFB (80.7%). An IOFB was positively associated with Ocular Trauma Score grade 1 or 2 (0–65) injuries (odds ratio [OR], 1.58; 95% CI, 1.07–2.38; P = 0.01). There were 130 eyes (78.33%) that had recorded time from initial visual acuity to final visual acuity and it ranged from 8 to 2421 days (mean, 433.24 days). Thirty-eight (25.16%; 95% CI, 18.89%–32.67%) eyes had no change in visual acuity, 98 (64.90%; 95% CI, 57.00%–72.07%) had improved visual acuity, and 15 (9.93%; 95% CI, 6.01%–15.84%) had decreased visual acuity. IOFB was not found to predict final visual acuity of <20/200 in multivariate analysis when other injury features were known (P = 0.1). Pars plana vitrectomy was completed on 124 eyes (74.70%). Removal of IOFB was performed in 118 eyes (71.08%; average of 31.67 days after initial injury) with a delayed procedure occurring after primary closure and antibiotics owing to a lack of surgical capacity in Iraq and Afghanistan. Retinal detachment occurred in 48 eyes (28.92%) and proliferative vitreoretinopathy in 44 eyes (26.5%). Conclusions IOFBs occur frequently in combat ocular trauma and are significantly associated with more severe injuries. However, IOFBs were not found to be a significant risk factor for visual acuity of <20/200.

    更新日期:2018-07-21
  • Chemodenervation for the Treatment of Facial Dystonia
    Ophthalmology (IF 7.479) Pub Date : 2018-04-10
    Jurij R. Bilyk, Michael T. Yen, Elizabeth A. Bradley, Edward J. Wladis, Louise A. Mawn

    PurposeTo review the medical literature on the outcomes and complications of various Food and Drug Administration-approved botulinum toxins for benign essential blepharospasm (BEB) and hemifacial spasm (HFS).MethodsLiterature searches were last conducted in February 2017 in PubMed for articles published in English and in the Cochrane Library database without language limitations; studies published before 2000 were excluded. The combined searches yielded 127 citations. Of these, 13 articles were deemed appropriate for inclusion in this assessment, and the panel methodologist assigned ratings to them according to the level of evidence.ResultsA combined total of 1523 patients (1143 with BEB and 380 with HFS) were included in the 13 studies. Five studies provided level I evidence, 2 studies provided level II evidence, and 6 studies provided level III evidence. Pretarsal injections were more efficacious than preseptal injections (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher response rate on clinical scales (P < 0.05) and a longer duration of maximum response for both HFS and BEB. Patients with HFS require lower overall doses of onabotulinumtoxinA than patients with BEB for a similar duration of effect. Adverse events were dose related, and they occurred more frequently in patients who were given more units.ConclusionsLevel I evidence supports the efficacy of Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals, Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2 level II studies in this review are limited by differences in the methodologies used. Higher doses of Botox and Dysport result in more adverse events. Repeated treatments using Botox seem to maintain efficacy for treatment of facial dystonias over a follow-up period of at least 10 years, based on level III evidence.

    更新日期:2018-07-14
  • Phase 2 Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis
    Ophthalmology (IF 7.479) Pub Date : 2018-04-10
    Stefano Bonini, Alessandro Lambiase, Paolo Rama, Francesco Sinigaglia, Marcello Allegretti, Wendy Chao, Flavio Mantelli

    PurposeTo evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation.DesignPhase 2 multicenter, randomized, double-masked, vehicle-controlled trial.ParticipantsPatients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye.MethodsThe REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat.Main Outcome MeasuresCorneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining).ResultsAt week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 μg/ml (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P < 0.001) and 58.0% receiving rhNGF 20 μg/ml (+38.4%; 97.06% CI, 18.96–57.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 μg/ml (+31.4%; 97.06% CI, 11.25–51.49; P = 0.001) and 74.0% receiving rhNGF 20 μg/ml (+30.9%; 97.06% CI, 10.60–51.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient.ConclusionsTopical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK.

    更新日期:2018-07-14
  • 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:2018-07-14
  • 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:2018-07-14
  • 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:2018-07-14
  • Steroids versus No Steroids in Nonarteritic Anterior Ischemic Optic Neuropathy
    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:2018-07-14
  • 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:2018-07-14
  • 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
  • Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration
    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:2018-07-14
  • 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:2018-07-14
  • 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:2018-07-14
  • Management of Acute Retinal Ischemia
    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:2018-07-14
  • 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
    Matthias M. Mauschitz, Pieter W.M. Bonnemaijer, Kersten Diers, Franziska G. Rauscher, Tobias Elze, Christoph Engel, Markus Loeffler, Johanna Maria Colijn, M. Arfan Ikram, Johannes R. Vingerling, Katie M. Williams, Christopher J. Hammond, Catherine Creuzot-Garcher, Alain M. Bron, Rufino Silva, Sandrina Nunes, Cécile Delcourt, Audrey Cougnard-Grégoire, Jennyfer Zerbib

    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:2018-07-14
  • Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension
    Ophthalmology (IF 7.479) Pub Date : 2018-07-12
    Angelo P. Tanna, Mark Johnson

    In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the 1990s and systematically pursued, exposing novel cellular and molecular mechanisms of intraocular pressure (IOP) regulation. The critical discovery that pharmacologic manipulation of the cytoskeleton of outflow pathway cells decreased outflow resistance placed a spotlight on the Rho kinase pathway that was known to regulate the cytoskeleton. Ultimately, a search for Rho kinase inhibitors led to the discovery of several molecules of therapeutic interest, leaving us today with 2 new ocular hypotensive agents approved for clinical use: ripasudil in Japan and netarsudil in the United States. These represent members of the first new class of clinically useful ocular hypotensive agents since the US Food and Drug Administration approval of latanoprost in 1996. The development of Rho kinase inhibitors as a class of medications to lower IOP in patients with glaucoma and ocular hypertension represents a triumph in translational research. Rho kinase inhibitors are effective alone or when combined with other known ocular hypotensive medications. They also offer the possibility of neuroprotective activity, a favorable impact on ocular blood flow, and even an antifibrotic effect that may prove useful in conventional glaucoma surgery. Local adverse effects, however, including conjunctival hyperemia, subconjunctival hemorrhages, and cornea verticillata, are common. Development of Rho kinase inhibitors targeted to the cells of the outflow pathway and the retina may allow these agents to have even greater clinical impact. The objectives of this review are to describe the basic science underlying the development of Rho kinase inhibitors as a therapy to lower IOP and to summarize the results of the clinical studies reported to date. The neuroprotective and vasoactive properties of Rho kinase inhibitors, as well as the antifibrotic properties, of these agents are reviewed in the context of their possible role in the medical and surgical treatment of glaucoma.

    更新日期:2018-07-12
  • Low-Concentration Atropine for Myopia Progression (LAMP) Study
    Ophthalmology (IF 7.479) Pub Date : 2018-07-06
    Jason C. Yam, Yuning Jiang, Shu Min Tang, Antony K.P. Law, Joyce J. Chan, Emily Wong, Simon T. Ko, Alvin L. Young, Clement C. Tham, Li Jia Chen, Chi Pui Pang

    PurposeLow-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period.DesignRandomized, placebo-controlled, double-masked trial.ParticipantsA total of 438 children aged 4 to 12 years with myopia of at least −1.0 diopter (D) and astigmatism of −2.5 D or less.MethodsParticipants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. Visual Function Questionnaire was administered at the 1-year visit.Main Outcome MeasuresChanges in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using generalized estimating equation.ResultsAfter 1 year, the mean SE change was −0.27±0.61 D, −0.46±0.45 D, −0.59±0.61 D, and −0.81±0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo groups, respectively (P < 0.001), with a respective mean increase in AL of 0.20±0.25 mm, 0.29±0.20 mm, 0.36±0.29 mm, and 0.41±0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98±2.82 D, 1.61±2.61 D, 0.26±3.04 D, and 0.32±2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03±1.02 mm and 0.58±0.63 mm in the 0.05% atropine group, 0.76±0.90 mm and 0.43±0.61 mm in the 0.025% atropine group, 0.49±0.80 mm and 0.23±0.46 mm in the 0.01% atropine group, and 0.13±1.07 mm and 0.02±0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group.ConclusionsThe 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year.

    更新日期:2018-07-08
  • Spectral-Domain OCT: Helping the Clinician Diagnose Glaucoma
    Ophthalmology (IF 7.479) Pub Date : 2018-07-07
    Teresa C. Chen, Ambika Hoguet, Anna K. Junk, Kouros Nouri-Mahdavi, Sunita Radhakrishnan, Hana L. Takusagawa, Philip P. Chen

    PurposeTo review the current published literature on the use of spectral domain (SD) OCT to help detect changes associated with the diagnosis of glaucoma.MethodsSearches of the peer-reviewed literature were conducted on June 11, 2014, November 7, 2016, August 8, 2017, and April 19, 2018, in the PubMed and Cochrane Library databases and included only articles published since the last glaucoma imaging Ophthalmic Technology Assessment, which included articles up until February 2006. The abstracts of these 708 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 74 articles were selected, and the panel methodologist (K.N.-M.) assigned ratings to them according to the level of evidence. Two articles were rated level I, 57 articles were rated level II, and the 15 level III articles were excluded.ResultsSpectral-domain OCT is capable of detecting damage to the retinal nerve fiber layer (RNFL), macula, and optic nerve in patients with preperimetric and perimetric glaucoma (level I and II evidence). The most commonly studied single parameter was RNFL thickness. Of note, RNFL thickness measurements are not interchangeable between instruments. Various commercially available SD OCT instruments have similar abilities to distinguish patients with known glaucoma from normal subjects. Despite different software protocols, all SD OCT instruments are able to detect the same typical pattern of glaucomatous RNFL loss that affects primarily the inferior, inferior temporal, superior, and superior temporal regions of the optic nerve (level II evidence). Across many SD OCT instruments, macular imaging also can detect a preferential inferior, inferior temporal, and superior temporal thinning in patients with glaucoma compared with controls. Best disc parameters for detecting glaucomatous nerve damage are global rim area, inferior rim area, and vertical cup-to-disc ratio. Studies suggest that newer reference-plane independent optic nerve parameters may have the same or better detection capability when compared with older reference-plane dependent disc parameters (level II evidence).ConclusionsStructural glaucomatous damage can be detected by SD OCT. Optic nerve, RNFL, and macular parameters can help the clinician distinguish the anatomic changes that are associated with patients with glaucoma when compared with normal subjects.

    更新日期:2018-07-08
  • Targeting Interleukin-23 in the Treatment of Noninfectious Uveitis
    Ophthalmology (IF 7.479) Pub Date : 2018-07-04
    Kathryn L. Pepple, Phoebe Lin

    The interleukin (IL)-23/IL-17 axis plays a central role in the pathogenesis of immune-mediated diseases such as psoriasis, psoriatic arthritis, Crohn’s disease, and uveitis. Therefore, targeting the IL-23/IL-17 axis has become the focus of multiple clinical trials for drug development in patients with autoimmune diseases. We briefly describe the biology of the IL-23/IL-17 axis and its relevance to the pathogenesis of experimental and clinical uveitis, and review the monoclonal antibody therapies targeting this pathway. Finally, 2 ongoing phase 2 trials of the anti–IL-23 biologic therapy ustekinumab (STELARA, Janssen Biotech Inc, Horsham, PA) in patients with noninfectious uveitis are introduced.

    更新日期:2018-07-05
  • Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy
    Ophthalmology (IF 7.479) Pub Date : 2018-07-03
    Susan B. Bressler, Wesley T. Beaulieu, Adam R. Glassman, Jeffrey G. Gross, Michele Melia, Eric Chen, Michael R. Pavlica, Lee M. Jampol,

    Purpose To identify baseline factors associated with change in visual acuity or development of vision-impairing central-involved diabetic macular edema (DME) over 2 years when treating proliferative diabetic retinopathy (PDR) with ranibizumab or panretinal photocoagulation (PRP). Design Post hoc analyses of randomized, multicenter clinical trial data. Participants Eyes completing the 2-year visit (n = 328) or without vision-impairing central-involved DME at baseline (n = 302) in Diabetic Retinopathy Clinical Research Network Protocol S. Methods Intravitreous ranibizumab (0.5 mg/0.05 ml) or PRP. Main Outcome Measures Change in visual acuity (area under the curve) and development of vision-impairing (20/32 or worse) central-involved DME over 2 years. Results After multivariable model selection with adjustment for baseline visual acuity and central subfield thickness, no factors were identified as associated with change in visual acuity or development of vision-impairing central-involved DME within the ranibizumab group. In the PRP group, worse change in visual acuity was more likely with higher hemoglobin A1c level (–0.6 letters per 1% increase; 95% confidence interval [CI], –1.2 to –0.1 letters; continuous P = 0.03), more severe diabetic retinopathy (difference between high-risk PDR or worse vs. moderate PDR or better, –2.8 letters [95% CI, –5.5 to –0.2 letters]; continuous P = 0.003), and higher mean arterial pressure (difference between ≥100 mmHg vs. <100 mmHg, –2.0 letters [95% CI, –4.6 to 0.5 letters]; continuous P = 0.009). Development of vision-impairing central-involved DME was more likely with higher hemoglobin A1c level (hazard ratio [HR] per 1% increase, 1.31 [95% CI, 1.13–1.52]; continuous P < 0.001), more severe diabetic retinopathy (HR for high-risk PDR or worse vs. moderate PDR or better, 1.46 [95% CI, 0.73–2.92]; continuous P = 0.03), and the presence of cystoid abnormalities within 500 μm of the macula center (HR, 2.90 [95% CI, 1.35–6.24]; P = 0.006). Conclusions For eyes managed with PRP, higher hemoglobin A1c level and more severe diabetic retinopathy were associated with less vision improvement and an increased risk of vision-impairing central-involved DME developing. When managing PDR with ranibizumab, eyes gained vision, on average, with no baseline characteristics identified as associated with visual acuity or central-involved DME outcomes.

    更新日期:2018-07-04
  • Long-Term Shape, Curvature, and Depth Changes of the Lamina Cribrosa after Trabeculectomy
    Ophthalmology (IF 7.479) Pub Date : 2018-06-28
    Aistė Kadziauskienė, Ernesta Jašinskienė, Rimvydas Ašoklis, Eugenijus Lesinskas, Tomas Rekašius, Jacqueline Chua, Ching-Yu Cheng, Jean Martial Mari, Michaël J.A. Girard, Leopold Schmetterer

    Purpose To evaluate changes in lamina cribrosa (LC) shape, curvature, and depth after trabeculectomy. Design Prospective, observational case series. Participants A total of 112 patients (118 eyes) with open- or closed-angle glaucoma undergoing trabeculectomy. Methods The optic nerve head was imaged using enhanced depth imaging spectral-domain OCT before trabeculectomy and at 6 follow-up visits throughout the first postoperative year. The anterior LC surface and Bruch’s membrane opening were marked in the serial horizontal B scans for the analysis of LC parameters using Morphology 1.0 software. Postoperative morphologic LC changes were assessed. Main Outcome Measures The postoperative LC global shape index (GSI), nasal-temporal (N-T) and superior-inferior (S-I) curvatures, and mean and sectoral LC depth (LCD). Results The mean LC GSI increased only during the early postoperative period (P = 0.02), resulting in a change toward the saddle-rut shape. There was a flattening of the LC curvature in N-T (P < 0.001) and S-I (P = 0.003) meridians 12 months after trabeculectomy. A shallowing of the mean and sectoral LCD from baseline was significant throughout the entire follow-up period (P < 0.001) and progressed up to postoperative month 6. Twenty-eight patients showed a deepening of the LC from baseline in at least 1 visit. Eyes with shallower LCD compared with baseline responded to intraocular pressure (IOP) reduction with greater movement anteriorly than eyes with deeper LCD (P = 0.002). Greater IOP reduction (P = 0.007), less retinal nerve fiber layer thinning over the year (P = 0.003), and more superiorly-inferiorly curved baseline LC (P = 0.001) were associated with an increase in GSI. Younger age and IOP reduction were related to LC shallowing (P < 0.001, P = 0.002) and N-T flattening (P < 0.001). Conclusions In most eyes, trabeculectomy resulted in long-term flattening and shallowing of the LC. However, in some eyes, LC deepened from baseline. Change in LC global shape appeared to be temporal. Reduction in IOP plays an important role in the early phase of LC change; however, in the later phase, LC remodeling may play a crucial role in view of stable IOP.

    更新日期:2018-06-30
  • A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open-Angle Glaucoma and Cataract : The HORIZON Study
    Ophthalmology (IF 7.479) Pub Date : 2018-06-23

    Objective To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months. Design Prospective, multicenter, single-masked, randomized controlled trial. Participants Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. Methods Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. Main Outcome Measures The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events. Results A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%–27.8%, P < 0.001). The mean reduction in 24-month unmedicated MDIOP was −7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and −5.3±3.9 mmHg in the NMS group (difference = −2.3 mmHg; 95% CI, −3.0 to −1.6; P < 0.001). The mean number of medications was reduced from 1.7±0.9 at baseline to 0.3±0.8 at 24 months in the HMS group and from 1.7±0.9 to 0.7±0.9 in the NMS group (difference = −0.4 medications; P < 0.001). There were no serious ocular adverse events related to the microstent, and no significant differences in safety parameters between the 2 groups. Conclusions This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.

    更新日期:2018-06-25
  • Descemet Endothelial Thickness Comparison Trial : A Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty
    Ophthalmology (IF 7.479) Pub Date : 2018-06-23
    Winston Chamberlain, Charles C. Lin, Ariana Austin, Nicholas Schubach, Jameson Clover, Stephen D. McLeod, Travis C. Porco, Thomas M. Lietman, Jennifer Rose-Nussbaumer

    Purpose To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction. Design Patient and outcome-masked, randomized controlled clinical trial. Participants Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK. Methods Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery. Main Outcome Measures The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry. Results A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon Health & Science University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5–0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8–1.0 lines better; P < 0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2–0.7 lines better; P < 0.001). Average endothelial cell counts were 1963 cells/mm2 in DMEK and 2113 cells/mm2 in UT-DSAEK at 6 months (P = 0.17) and 1855 cells/mm2 in DMEK and 2070 cells/mm2 in UT-DSAEK at 12 months (P = 0.051). Intraoperative and postoperative complication rates were similar between groups. Conclusions Descemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.

    更新日期:2018-06-25
  • Baseline Lamina Cribrosa Curvature and Subsequent Visual Field Progression Rate in Primary Open-Angle Glaucoma
    Ophthalmology (IF 7.479) Pub Date : 2018-06-23
    Ahnul Ha, Tai Jun Kim, Michael J.A. Girard, Jean Martial Mari, Young Kook Kim, Ki Ho Park, Jin Wook Jeoung

    Purpose To investigate the relationship between the degree of posterior bowing of the lamina cribrosa (LC) at baseline and the rate of subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG). Design Prospective, observational study. Participants One hundred one early-stage (VF mean deviation [MD], –5.0 to –0.01 dB) POAG eyes that met the following conditions: (1) follow-up longer than 3.5 years, (2) more than 5 reliable standard automated perimetry tests, and (3) medically well-controlled intraocular pressure during follow-up. Methods All participants underwent swept-source OCT scanning of the LC at baseline. The area enclosed by a vertical line at the anterior laminar insertion, anterior LC plane, and reference plane of Bruch’s membrane opening (BMO) was divided by D (distance between the 2 cross-points made by vertical lines drawn from the anterior laminar insertion to the reference plane of BMO) to approximate the LC depth (LCD). The difference between the LCD and mean anterior laminar insertion depth was defined as the LC curvature index (LCCI). To consider the steepness of the LC curve, the adjusted LCCI (aLCCI) was calculated as LCCI divided by D and multiplied by 100. The mean LCD (mLCD), mean LCCI (mLCCI), and mean aLCCI (maLCCI) were computed by averaging the measurements on 12 radial scans. The subsequent MD slope and associated factors were analyzed. Main Outcome Measures Lamina cribrosa parameters and subsequent MD slope. Results The participants’ mean baseline MD was –3.8 ± 3.4 dB. The mean baseline mLCD, mLCCI, and maLCCI were 419.0 ± 111.2 μm, 76.4 ± 29.0 μm, and 4.8 ± 1.9, respectively. A greater MD slope was associated with a greater baseline maLCCI (P < 0.001). We found a statistically significant breakpoint for the maLCCI (4.12) above which a larger maLCCI showed a steeper MD slope (P < 0.001). Analysis by age revealed that significantly more VF progression with maLCCI changes occurred in the relatively younger group (≤69 years; P = 0.043). Conclusions The baseline maLCCI showed a significant correlation with the rate of subsequent VF deterioration. This suggests that, in POAG eyes with greater posterior bowing of the LC, the axons of retinal ganglion cells may be more vulnerable to further glaucomatous injury.

    更新日期:2018-06-25
  • Can Macula and Optic Nerve Head Parameters Detect Glaucoma Progression in Eyes with Advanced Circumpapillary Retinal Nerve Fiber Layer Damage?
    Ophthalmology (IF 7.479) Pub Date : 2018-06-19
    Fabio Lavinsky, Mengfei Wu, Joel S. Schuman, Katie A. Lucy, Mengling Liu, Youngseok Song, Julia Fallon, Maria de Los Angeles Ramos Cadena, Hiroshi Ishikawa, Gadi Wollstein

    Purpose To evaluate the ability of OCT optic nerve head (ONH) and macular parameters to detect disease progression in eyes with advanced structural glaucomatous damage of the circumpapillary retinal nerve fiber layer (cRNFL). Design Longitudinal study. Participants Forty-four eyes from 37 patients with advanced average cRNFL damage (≤60 μm) followed up for an average of 4.0 years. Methods All patients were examined with spectral-domain OCT and visual field (VF) assessment during at least 4 visits. Main Outcome Measurements Visual field mean deviation (MD) and VF index. OCT cRNFL (average, superior, and inferior quadrants), ganglion cell–inner plexiform layer (GCIPL) (average, superior, and inferior), rim area, cup volume, average cup-to-disc (C:D) ratio, and vertical C:D ratio. Results At baseline, patients had a median VF MD of –10.18 dB and mean cRNFL of 54.55±3.42 μm. The rate of change for MD and VF index were significant. No significant rate of change was noted for cRNFL, whereas significant (P < 0.001) rates were detected for GCIPL (–0.57±0.05 μm/year) and ONH parameters such as rim area (–0.010±0.001 mm2/year). Conclusions Macula GCIPL and ONH parameters may be useful in tracking progression in patients with advanced glaucoma.

    更新日期:2018-06-22
  • Detection of Bruch’s Membrane Opening in Healthy Individuals and Glaucoma Patients with and without High Myopia
    Ophthalmology (IF 7.479) Pub Date : 2018-06-19
    Feihui Zheng, Zhongheng Wu, Christopher K.S. Leung

    Purpose To determine the proportions of eyes with indiscernible Bruch’s membrane opening (BMO) in glaucoma patients and healthy individuals with and without high myopia and to investigate factors contributing to indiscernible BMO. Design Cross-sectional study. Participants Five hundred eyes from 315 participants, including 212 high myopic eyes (axial length [AL], ≥26 mm) from 80 glaucoma patients and 60 healthy individuals and 288 non-high myopic eyes (AL, <26 mm) from 96 glaucoma patients and 88 healthy individuals. Methods The optic disc was imaged by the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) using 24 equally spaced radial B-scans. The BMO was located independently by 2 trained observers and was recorded as discernible or indiscernible over 48 meridians in each eye. The BMO of a meridian was determined to be indiscernible when both observers failed to identify its location. The agreement between the observers was evaluated with κ statistics. Factors associated with indiscernible BMO were identified with multivariable, multilevel logistic regression modeling. Main Outcome Measures Proportions of eyes with indiscernible BMO and hazard ratios (HRs) of factors associated with indiscernible BMO. Results The agreement for assessment of BMO visibility between the observers was good (κ, 0.631; 95% confidence interval, 0.602–0.661). In the groups with and without high myopia, 32.1% and 8.2% of glaucomatous eyes had 1 or more meridians with indiscernible BMO, respectively. In the healthy eyes, the respective proportions were 28.0% and 3.9%. The proportions were significantly higher in eyes with high myopia compared to eyes without high myopia in the glaucoma group (P < 0.001) and the healthy group (P < 0.001). The temporal meridian, followed by the inferotemporal and superotemporal meridians, of the optic disc were the most frequent locations with indiscernible BMO. Increased AL, advanced glaucoma, β parapapillary atrophy, and young age were associated with an increased HR of indiscernible BMO (P ≤ 0.032). Conclusions A significant proportion of high myopic eyes have indiscernible BMO at the temporal, superotemporal, and inferotemporal meridians of the optic disc, which may compromise the measurement of neuroretinal rim in the diagnostic evaluation of glaucoma.

    更新日期:2018-06-22
  • Adrenal Suppression in Infants Treated with Topical Ocular Glucocorticoids
    Ophthalmology (IF 7.479) Pub Date : 2018-06-19
    Regitze Bangsgaard, Katharina M. Main, Gøril Boberg-Ans, Morten la Cour, Julie Lyng Forman, Birgitte Haargaard, Jens Folke Kiilgaard

    Purpose To analyze the incidence of adrenal suppression and the glucocorticoid (GC) dose per kilogram body weight given in infants treated with standard protocol for topical ophthalmic GCs after congenital cataract surgery. Design Retrospective, consecutive case series. Participants All children younger than 2 years of age who underwent operation for congenital cataract between January 2011 and May 2015 in 1 center. Methods Patient charts were reviewed to collect data on results and timing of a standard corticotropin (adrenocorticotropic hormone [ACTH]) stimulation test and GC dose per kilogram body weight. Main Outcome Measures Incidence of adrenal suppression in children tested on GC treatment. Glucocorticoid dose per kilogram body weight. Results Among 26 consecutive infants, 15 (58%) were tested while they were still on GC treatment. Ten of these 15 infants (67%) had adrenal suppression, 2 of whom had obvious clinical signs of Cushing's syndrome and 1 of whom had signs of Addisonian crises during general anesthesia. Eleven of the 26 infants (42%) were tested at a median time of 21 days (range, 6–89) after treatment cessation, and they all had normal test results. Children with suppressed adrenal function had received cumulative GC doses per body weight that were significantly higher the last 5 days before testing compared with children with normal test results. Infants with adrenal suppression were treated with hydrocortisone replacement therapy. Adrenal function recovered after a median of 3.1 months (range, 2.3 months to 2.3 years). Conclusions Two thirds of the infants tested during treatment with a standard GC protocol after congenital cataract surgery showed adrenal suppression. There was a significant association between the cumulative daily dose of GCs and the test result. Because adrenal suppression is a serious but treatable condition, we recommend a systematic assessment of adrenal function in infants treated with doses of topical ocular GCs comparable to our regimen and careful evaluations of other treatment regimens.

    更新日期:2018-06-22
  • The Associations between Near Visual Activity and Incident Myopia in Children : A Nationwide 4-Year Follow-up Study
    Ophthalmology (IF 7.479) Pub Date : 2018-06-20
    Po-Wen Ku, Andrew Steptoe, Yun-Ju Lai, Hsiao-Yun Hu, Dachen Chu, Yung-Feng Yen, Yung Liao, Li-Jung Chen

    Objective This nationwide population-based study aimed to examine the prospective association between near visual activities and incident myopia in Taiwanese children 7 to 12 years old over a 4-year follow-up period. Design Prospective cohort design. Participants There were 1958 children aged 7 to 12 years from the Taiwan 2009 National Health Interview Survey who were linked to the 2009 through 2013 claims data from the National Health Insurance system. Methods Multivariable Cox proportional hazard models were used to estimate the associations between 3 types of near visual activities in sedentary posture, namely reading (< 0.5, 0.5-0.9, ≥1.0 hours per day [h/d]), use of computer, Internet, and games (<0.5, 0.5-0.9, ≥1.0 h/d), and “cram school” attendance (<0.5, 0.5-1.9, ≥2.0 h/d), and incident myopia. Main Outcome Measures Prevalent myopia was defined as those who had ≥2 ambulatory care claims (International Classification of Diseases code 367.1) in 2008-2009. Incident myopia was defined by those who had at least 2 ambulatory care claims (International Classification of Diseases code 367.1) during the 4-year follow-up period (2010-2013) after excluding prevalent cases. Results Overall, 26.8% of children had myopia at baseline, and 27.7% of those without myopia at baseline developed incident myopia between 2010 and 2013. On average, they spent 0.68±0.86 h/d on computer/Internet use, 0.63±0.67 h/d on reading, and 2.78±3.53 h/d on cram school. The results showed that children attending cram schools ≥2 h/d (hazard ratio, 1.31; 95% confidence interval, 1.03-1.68) had a higher risk of incident myopia. The effects of these activities remained similar in sensitivity analyses. Conclusions Cram school attendance for ≥2 h/d may increase the risk of children’s incident myopia. This effect may be due to increased near visual activity or reduced time outdoors.

    更新日期:2018-06-22
  • Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy : The PLACE Trial
    Ophthalmology (IF 7.479) Pub Date : 2018-06-14
    Elon H.C. van Dijk, Sascha Fauser, Myrte B. Breukink, Rocio Blanco-Garavito, Joannes M.M. Groenewoud, Jan E.E. Keunen, Petrus J.H. Peters, Greet Dijkman, Eric H. Souied, Robert E. MacLaren, Giuseppe Querques, Susan M. Downes, Carel B. Hoyng, Camiel J.F. Boon

    Purpose To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC). Design Open-label, multicenter, randomized controlled clinical trial. Participants Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging. Methods Eligible patients were randomized in a 1:1 allocation ratio. Treatment was evaluated during a follow-up visit, and the same treatment was repeated in patients who still demonstrated subretinal fluid (SRF). Main Outcome Measures The primary end point was the complete disappearance of SRF at the first evaluation visit at 6 to 8 weeks after treatment. As a secondary outcome measure, we assessed this anatomic result at the final evaluation visit at 7 to 8 months after treatment. Other secondary outcomes covered functional improvement and included change in best-corrected visual acuity (BCVA; measured in Early Treatment Diabetic Retinopathy Study [ETDRS] letters), retinal sensitivity (measured using microperimetry), and vision-related quality of life using a validated questionnaire. Results Between November 2013 and September 2016, 179 patients were included: 89 patients were assigned randomly to half-dose PDT, and 90 were assigned randomly to HSML treatment. At their first evaluation visit, SRF had resolved in 51.2% and 13.8% of patients, respectively (P < 0.001). At their final evaluation visit, a significantly higher percentage of PDT-treated patients demonstrated no SRF (67.2% vs. 28.8%; P < 0.001). Moreover, at the first evaluation visit, the PDT-treated patients showed a significantly higher increase in BCVA (+4.60±6.62 ETDRS letters vs. +1.39±8.99 ETDRS letters; P = 0.011), and a significantly higher increase in retinal sensitivity on microperimetry (+2.01±3.04 dB vs. +0.92±3.65 dB; P = 0.046); however, the improvement in vision-related quality of life was similar (score of +2.87±8.35 vs. +2.56±7.36, respectively; P = 0.800). Conclusions Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement.

    更新日期:2018-06-14
  • Balloon Dacryoplasty for Congenital Nasolacrimal Duct Obstruction : A Report by the American Academy of Ophthalmology
    Ophthalmology (IF 7.479) Pub Date : 2018-06-07
    Edward J. Wladis, Vinay K. Aakalu, Michael T. Yen, Jurij R. Bilyk, Rachel K. Sobel, Louise A. Mawn

    Purpose To identify the efficacy and adverse event rates of balloon dacryoplasty in cases of congenital nasolacrimal duct obstruction in children who fail to respond to an initial nasolacrimal duct probing. Methods A literature search was last performed in September 2017 in the PubMed database to identify all reports of balloon dacryoplasty. All searches up to and including the last search were limited to the English language, and they yielded 104 articles that were assessed for relevancy. Thirty-six articles were selected for full review, and 8 of these were selected for inclusion in this assessment and assigned a quality of evidence rating by the panel methodologist. Results Three of the 8 studies included in this assessment were rated level II, and 5 were rated level III. Success rates varied from 75% to 100%. Only 2 complications were identified, and these were cases of self-limited postoperative emesis. The 2 studies that compared balloon dacryoplasty with lacrimal stenting reported that outcomes were comparable between the 2 techniques. Conclusions Although level I evidence was not available, the studies that were uncovered in the literature review indicate that balloon dacryoplasty is a safe, effective procedure to address congenital nasolacrimal duct obstruction that persists after standard probings. The outcomes of this intervention are similar to those of lacrimal stenting, and the absence of an implanted stent theoretically reduces the risk of complications.

    更新日期:2018-06-07
  • A Dosing Study of Bevacizumab for Retinopathy of Prematurity : Late Recurrences and Additional Treatments
    Ophthalmology (IF 7.479) Pub Date : 2018-06-07
    David K. Wallace, Trevano W. Dean, Mary Elizabeth Hartnett, Lingkun Kong, Lois E. Smith, G. Baker Hubbard, Mary Lou McGregor, Catherine O. Jordan, Iason S. Mantagos, Edward F. Bell, Raymond T. Kraker

    Purpose Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Design Masked, multicenter, dose de-escalation study. Participants A total of 61 premature infants with type 1 ROP. Methods If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Main Outcome Measures Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Results Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%–54%) received additional treatment: 3 (5%; 95% CI, 1%–14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%–30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%–30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%–52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%–52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%–55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%–31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Conclusions Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

    更新日期:2018-06-07
  • Development of Topographic Scoring System for Identifying Glaucoma in Myopic Eyes : A Spectral-Domain OCT Study
    Ophthalmology (IF 7.479) Pub Date : 2018-06-07
    Sung Uk Baek, Ko Eun Kim, Young Kook Kim, Ki Ho Park, Jin Wook Jeoung

    Purpose To develop a new scoring system that uses topographic diagnostic signs of spectral-domain (SD) OCT to enhance glaucoma diagnostic performance for myopic eyes and to validate the system’s diagnostic ability. Design Cross-sectional study. Participants A total of 517 patients (517 eyes; spherical equivalent [SE] <–1.0 diopters [D] or axial length >24.0 mm), including 175 highly myopic eyes (SE <–6.0 D or axial length >26.0 mm), were recruited and divided into 2, training (241 eyes) and validation (276 eyes) test sets. Methods Retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL) topographic signs were selected based on the morphologic patterns of RNFL (size, shape, location, and agreement between deviation and thickness maps) and GCIPL (size, shape, location, color tone, agreement between maps, and step sign) abnormalities indicative of higher likelihood of myopic glaucoma on deviation and thickness maps. The diagnostic score was compiled according to the sensitivity, specificity, and positive likelihood ratio (PLR) of each diagnostic sign using the training set. The area under the receiver operating characteristic curve (AUC) was plotted and compared between the OCT-provided parameters and the scoring system in the validation set. Main Outcome Measures The diagnostic performance of a new scoring system as validated by AUC. Results Among all of the RNFL and GCIPL parameters, the presence of temporal hemifield asymmetry on the GCIPL thickness map (PLR, 5.98) showed the highest diagnostic ability, followed by location of the RNFL defect (PLR, 5.79) and color tone of the GCIPL defect (PLR, 5.04). The AUC of the topographic scoring system in myopic eyes was 0.979, which was significantly higher than those of the inferior (0.895; P < 0.001) and average (0.894; P < 0.001) RNFL thickness parameters. For highly myopic eyes, the scoring system (AUC, 0.983) also showed a higher diagnostic performance than that of the RNFL and GCIPL thickness parameters (all P < 0.001). Conclusions Our scoring system including OCT topographic parameters demonstrated to be beneficial for clinicians to differentiate real glaucomatous damage from myopic healthy eyes. Our results support the value of using multitopographic OCT parameters for detecting glaucoma in myopic eyes.

    更新日期:2018-06-07
  • The DISCOVER Study 3-Year Results
    Ophthalmology (IF 7.479) Pub Date : 2018-03-02
    Justis P. Ehlers, Yasha S. Modi, Paula E. Pecen, Jeff Goshe, William J. Dupps, Aleksandra Rachitskaya, Sumit Sharma, Alex Yuan, Rishi Singh, Peter K. Kaiser, Jamie L. Reese, Carmen Calabrise, Allison Watts, Sunil K. Srivastava

    Purpose To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. Design Prospective, consecutive case series. Participants Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. Methods The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. Main Outcome Measures Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. Results Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%–98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%–49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%–33.0%). Conclusions The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

    更新日期:2018-06-03
  • Choroidal Microvasculature Dropout Is Associated with Progressive Retinal Nerve Fiber Layer Thinning in Glaucoma with Disc Hemorrhage
    Ophthalmology (IF 7.479) Pub Date : 2018-03-02
    Hae-Young Lopilly Park, Jin Woo Kim, Chan Kee Park

    Objective We used OCT angiography (OCT-A) to investigate parapapillary choroidal microvasculature dropout (MvD) in glaucomatous eyes with or without disc hemorrhage (DH), and the association with changes in retinal nerve fiber layer (RNFL) thickness. Design An observational case-control study. Participants Eighty-two open-angle glaucoma (OAG) eyes with DH and 68 OAG eyes without DH that underwent at least 4 serial OCT examinations were included. Methods MvD was defined as complete loss of microvasculature within the choroidal layer of the parapapillary region, as revealed by standardized assessment of OCTA-derived density maps of the vessels of the optic nerve head. The circumferential extent of MvD was measured on OCT-A images. The RNFL thinning rate was calculated using a linear mixed model. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between groups stratified by DH and MvD. Main Outcome Measures MvD detection rate, the extent of MvD as measured by the MvD angle, and RNFL thinning rate. Results MvD was found in 38 (46.3%) eyes with DH at the prior DH site, which was found in only 20 (29.4%) eyes without DH, which was significantly different between the 2 groups (P = 0.025). Patients with progressive glaucoma exhibited significantly more MvD than the stable patients in both DH and no-DH groups. There were statistically significant differences between groups subdivided by the presence of DH and MvD as assessed by Kaplan-Meier analysis (log-rank test, P < 0.001). The angle of MvD was significantly greater in eyes with recurrent DH compared with eyes with single DH. Presence of DH, recurrent DH, and presence of MvD were factors associated with progressive RNFL thinning. Conclusions We found that MvD was frequent in progressive OAG eyes on the choroidal map of OCT-A, which was more frequently found at the prior DH locations in eyes with DH. This means that observing the presence of MvD using OCT-A may provide a biomarker for glaucoma progression, especially in eyes with DH.

    更新日期:2018-06-03
  • Laser Peripheral Iridotomy in Primary Angle Closure
    Ophthalmology (IF 7.479) Pub Date : 2018-03-02
    Sunita Radhakrishnan, Philip P. Chen, Anna K. Junk, Kouros Nouri-Mahdavi, Teresa C. Chen

    Purpose To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). Methods Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. Results Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2% to 57% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0%-8% of PAC suspect (PACS), 42% to 67% of PAC, 21% to 47% of acute PAC (APAC), and 83%-100% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0% to 0.3% per year in PACS and 0% to 4% per year in PAC. Complications after LPI included IOP spike (8–17 mmHg increase from baseline in 6%–10%), dysphotopsia (2%–11%), anterior chamber bleeding (30%–41%), and cataract progression (23%–39%). Conclusions Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.

    更新日期:2018-06-03
  • Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs
    Ophthalmology (IF 7.479) Pub Date : 2018-03-02
    Zhixi Li, Yifan He, Stuart Keel, Wei Meng, Robert T. Chang, Mingguang He

    Purpose To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs. Design A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs. Participants We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm. Methods This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm. Main Outcome Measures The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON. Results In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%). Conclusions A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results.

    更新日期:2018-06-03
  • Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema
    Ophthalmology (IF 7.479) Pub Date : 2018-03-07
    Lee M. Jampol, Adam R. Glassman, Danni Liu, Lloyd Paul Aiello, Neil M. Bressler, Elia J. Duh, Susan Quaggin, John A. Wells, Charles C. Wykoff

    Purpose To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. Design Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. Participants Participants with available plasma samples (N = 436). Methods Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. Main Outcome Measures Changes in the natural log (ln) of plasma VEGF levels. Results Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar. Conclusions These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.

    更新日期:2018-06-03
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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