Medicare incentive payments to U.S. ophthalmologists for use of electronic health records: 2011-2016 Ophthalmology (IF 7.479) Pub Date : 2019-02-13 Michael V. Boland, Thomas S. Hwang, Michele C. Lim, Jessica L. Peterson, Flora Lum, Aaron Y. Lee
PurposeTo investigate ophthalmologists’ rate of attestation to meaningful use (MU) of their electronic health record (EHR) systems in the Medicare EHR Incentive Program and their continuity and success in receiving payments in comparison with other specialties.DesignAdministrative database study.ParticipantsEligible professionals participating in the Medicare EHR Incentive Program.MethodsBased on publicly available data sources, subsets of payment and attestation data were created for ophthalmologists and for other specialties. The number of eligible professionals attesting was determined using the attestation data for each year and stage of the program. The proportion of attestations by EHR vendor was calculated using all attestations for each vendor.Main Outcome MeasuresNumbers of ophthalmologists attesting by year and stage of the Medicare EHR Incentive Program, incentive payments, and number of attestations by EHR vendor.ResultsIn the peak year of participation, 51.6% of ophthalmologists successfully attested to MU, compared with 37.1% of optometrists, 50.2% of dermatologists, 54.5% of otolaryngologists, and 64.4% of urologists. Across the 6 years of the program, ophthalmologists received an average of $17 942 in incentive payments compared with $11 105 for optometrists, $16 617 for dermatologists, $20 203 for otolaryngologists, and $23 821 for urologists. Epic and Nextgen were the most frequently used EHRs for attestation by ophthalmologists.Conclusions:Ophthalmology as a specialty performed better than optometry and dermatology, but worse than otolaryngology and urology, in terms of the proportion of eligible professionals attesting to MU of EHRs. Ophthalmologists were more likely to remain in the program after their initial year of attestation compared with all eligible providers. The top 4 vendors accounted for 50% of attestations by ophthalmologists.
Ocular Immune-Related Adverse Events of Immunotherapy—A Single-Site Case Series Ophthalmology (IF 7.479) Pub Date : 2019-02-06 Jenna M. Kim, Miguel A. Materin, Mario Sznol, Harriet Kluger, Sarah Weiss, Jessica Chow, Kathleen Stoessel, Ninani Kombo, Lucian Del Priore, Renelle Pointdujour-Lim
Nivolumab and ipilimumab are immunotherapy agents used to treat various cancers. Ophthalmologists should be aware of the rare but diverse immune-related adverse events (IRAE) from these treatments. To the authors’ knowledge, this is the largest case series of nivolumab/ipilimumab-associated ophthalmic IRAE.
Agreement and Predictors of Discordance of Six Visual Field Progression Algorithms Ophthalmology (IF 7.479) Pub Date : 2019-02-04 Osamah J. Saeedi, Tobias Elze, Loris D’Acunto, Ramya Swamy, Vikram Hegde, Surabhi Gupta, Amin Venjara, Joby Tsai, Jonathan S. Myers, Sarah R. Wellik, Carlos Gustavo De Moraes, Louis R. Pasquale, Lucy Q. Shen, Michael V. Boland
Purpose To determine the agreement of six established visual field progression algorithms in a large dataset of visual fields from multiple institutions and to determine predictors of discordance amongst these algorithms. Design Retrospective Longitudinal Cohort Subjects, Participants, and/or Controls: Visual fields from five major eye care institutions in the United States. This analysis included a subset of eyes with at least five SITA-Standard 24-2 visual fields that met our reliability criteria. Of a total of 831,240 fields, a subset of 90,713 visual fields of 13,156 eyes of 8,499 patients met the inclusion criteria. Methods Six commonly used visual field progression algorithms (mean deviation slope, visual field index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen’s Kappa coefficient. Bivariate and multivariable analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). Main Outcome Measures Agreement and discordance between algorithms Results Individual algorithms showed poor to moderate agreement with each other when compared directly (Kappa range: 0.12 – 0.52). 11.7% of eyes progressed based on at least four algorithms. Major predictors of discordance, or lack of agreement among algorithms were more depressed initial MD (P <0.01) and older age at first available visual field (P < 0.01). A greater number of visual fields (P<0.01), more years of follow up (P < 0.01) and eye care institution (P = 0.03) were also associated with discordance. Conclusions This extremely large comparative series demonstrates that existing algorithms have limited agreement, and that agreement varies with clinical parameters including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying “big data” results to individual practices.
Evidence of Müller Glial Dysfunction in Patients with Aquaporin-4 Immunoglobulin G–Positive Neuromyelitis Optica Spectrum Disorder Ophthalmology (IF 7.479) Pub Date : 2019-02-01 Yuyi You, Ling Zhu, Ting Zhang, Ting Shen, Ariadna Fontes, Con Yiannikas, John Parratt, Joshua Barton, Angela Schulz, Vivek Gupta, Michael H. Barnett, Clare L. Fraser, Mark Gillies, Stuart L. Graham, Alexander Klistorner
Purpose To compare functional and structural changes in the retina in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Design Cross-sectional study; biochemical study of human retinas. Participants A total of 181 participants, including 22 consecutive patients (44 eyes) with NMOSD, 131 patients (262 eyes) with multiple sclerosis (MS), and 28 normal subjects (56 eyes). In addition, 8 eyeballs from healthy donors were used for biochemical analysis. Methods Full-field electroretinography (ERG) and spectral-domain OCT were performed in all the subjects. Topography of AQP4 expression and Müller glial distribution were analyzed using Western blotting and immunohistochemistry. Main Outcome Measures Full-field ERG parameters, including amplitudes and peak times. Tissue volume of each of the retinal layers at the fovea by OCT segmentation. Levels of AQP4 expression at different retinal regions. Results The b-wave amplitude was significantly reduced in patients with AQP4+ NMOSD in scotopic ERGs (compared with AQP4− subjects, patients with MS, and normal controls), but not in photopic ERGs. Further analysis showed that this b-wave change was mainly caused by reduction of the slow PII component, suggesting specific Müller cell dysfunction. We also found thinning of specific retinal layers at the fovea in patients with AQP4+ NMOSD, in the Henle fiber outer nuclear layer (HFONL) and the inner segment (IS) layer, but not in the inner nuclear layer (INL), outer plexiform layer (OPL), or outer segment (OS) layer. Furthermore, there was a significant association between foveal HFONL-IS complex thinning and scotopic b-wave amplitude reduction (P = 0.005∼0.01, fixed-effects model). Western blotting demonstrated that Müller cell–specific AQP4 was expressed at a higher level at the fovea than the peripheral retina. Immunohistochemical studies revealed that the specific foveal thinning reflected the topography of AQP4 expression and Müller glial distribution in the human macula. Conclusions This study provides in vivo structural and functional evidence of Müller glial dysfunction in eyes of patients with AQP4+ NMOSD. Topography of retinal structural change is supported by distribution of Müller cells and patterns of AQP4 expression. The study suggests that visual electrophysiology and retinal imaging could be useful biomarkers to assess the potential retinal astrocytopathy in NMOSD.
Autologous Retinal Transplant For Refractory Macular Holes: Multicenter International Collaborative Study Group Ophthalmology (IF 7.479) Pub Date : 2019-01-31 Dilraj S. Grewal, Steve Charles, Barbara Parolini, Kazuaki Kadonosono, Tamer H. Mahmoud
Purpose To report the structural and functional outcomes of the autologous neurosensory retinal transplant for closure of refractory large macular holes. Design Multicenter retrospective consecutive case series Participants Forty-one eyes of 41 patients (27 female and 14 male) with a full thickness macular hole refractory to prior vitrectomy with internal limiting membrane peel and tamponade. Methods All patients underwent pars-plana vitrectomy, autologous neurosensory retinal transplant with either gas, silicone oil tamponade, or short-term Perfluoro-n-octane heavy-liquid tamponade. All patients had at least six-months follow up. Main Outcome Measures Anatomic closure of macular hole, change in ellipsoid zone (EZ) and external limiting membrane (ELM) defect on optical coherence tomography (OCT), visual acuity (VA) recovery, and surgical complications were analyzed. Results Mean number of prior surgeries was 1.5±0.94 (range 1-3) and patients were followed for a mean of 11.1±7.7 months (range, 6–36 months). Complete anatomic closure of macular hole by OCT was achieved in 36/41 eyes (87.8%). Mean corrected VA (logMAR) improved (p=0.03) from 1.11±0.66 (range 0.48 to 3) to 1.03 ± 0.51 (range 0.1 to 2) at the last post-operative visit. VA improved (≥0.3 logMAR units) in 15 eyes (36.6%), was stable in 17 eyes (41.5%) and worsened in 9 eyes (21.9%). Among eyes with anatomic closure, VA improved in 52.3% and worsened in 13.8%, while in those without closure, VA worsened in 20% and improved in none. Mean preoperative largest basal diameter was 1468.1±656.4 μm (range 621-2600μm) and mean inner-opening diameter was 825 ± 422.5 μm (range 336-1649 μm). Mean preoperative EZ defect was 1777.3 ± 513.8 μm (range 963-2808μm) which reduced to 1370 ± 556.9 μm (range 288-2000 μm) at final followup (p=0.007). Mean preoperative ELM was 1681.5 ± 429 μm (range 1172-2606 μm) which reduced to 1408.5 ± 571.2 μm (range 200-2000 μm) at final follow up (p=0.017). Major post-operative complications were retinal detachment (n=1) and vitreous hemorrhage (n=1) There were no cases of proliferative vitreoretinopathy, endophthalmitis, suprachoroidal hemorrhage or choroidal neovascularization. Conclusion The autologous retinal transplant technique offers a high degree of anatomical success and proved safe in this initial experience for closure of refractory macular holes.
Optical Coherence Tomography-based Diagnostic Criteria for Different Stages of Myopic Maculopathy Ophthalmology (IF 7.479) Pub Date : 2019-01-29 Yuxin Fang, Ran Du, Natsuko Nagaoka, Tae Yokoi, Kosei Shinohara, Xian Xu, Hiroyuki Takahashi, Yuka Onishi, Takeshi Yoshida, Kyoko Ohno-Matsui
Purpose To analyze the choroidal thickness (CT) of each type of myopic maculopathy, and to establish an OCT-based classification of myopic maculopathy. Design Retrospective, hospital-based, cross-sectional study. Participants Highly myopic (HM) eyes that were examined by swept-source OCT. Methods The CT was measured at the subfovea and at 3 mm nasal, temporal, superior, and inferior to the fovea. Myopic maculopathy was classified as tessellation, diffuse atrophy, patchy atrophy, and macular atrophy (MA) based on the fundus photographs. Diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). Main Outcome Measures The CT of each type of myopic maculopathy and cut-off value for diagnosis of diffuse atrophy. Results We studied 1487 eyes of 884 patients (mean age: 58 years; mean axial length [AxL]: 29.9 mm). Subfoveal CT decreased with an increase in the severity of the myopic maculopathy. The mean subfoveal CT in HM eyes with normal fundus was 274.5 μm, with tessellation was 129.1 μm, with PDCA was 84.6 μm, with MDCA was 50.2 μm, with patchy atrophy was 48.6 μm, with choroidal neovascularization–related MA was 27.3 μm, and with patchy atrophy–related MA was 3.5 μm. Using receiver operating characteristic curves, the optimal CT to predict the presence of PDCA was 56.5 μm nasally, and the CT to predict the presence of MDCA was 62 μm subfoveally. The subfoveal CT was not significantly different in eyes with MDCA and patchy atrophy. A decrease of the subfoveal CT was associated with an older age (P < 0.001), female sex (P = 0.048), longer AxL (P < 0.001), presence of myopic maculopathy (P < 0.001), and presence of CNV (P = 0.001). The subfoveal CT was not a significant predictive factor of visual acuity. Conclusions Progressive and continuous choroidal thinning plays a key role in the progression from no maculopathy to tessellation and to diffuse atrophy. The cut-off value of CT can be used for diagnosing PDCA and MDCA. For progression from MDCA to patchy atrophy, factors other than further choroidal thinning such as Bruch membrane defect may be involved. The subfoveal CT was not a predictor of visual acuity in HM eyes without CNV.
A Clinical Phase 2 Study to Assess Efficacy, Safety and Tolerability of CyclASol® for Treatment of Dry Eye Disease (DED) Ophthalmology (IF 7.479) Pub Date : 2019-01-28 David L. Wirta, Gail L. Torkildsen, Helen R. Moreira, John D. Lonsdale, Joseph B. Ciolino, Garrit Jentsch, Michael Beckert, George Ousler, Philipp Steven, Sonja Krösser
Purpose To compare the efficacy, safety and tolerability of CyclASol® at two concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with Dry Eye Disease (DED). An open-label RestasisTM arm was included to allow a direct comparison with an approved therapy. Design An exploratory Phase 2, multicenter, randomized, vehicle controlled clinical trial, double-masked between CyclASol® and vehicle with an open-label comparator. Participants Two hundred and seven eligible patients with a history of dry eye were randomized 1:1:1:1 to one of four treatment arms (CyclASol® 0.05%, n=51; CyclASol® 0.1%, n=51; vehicle, n=52 and RestasisTM, n=53). Methods After a 2-week run-in period with twice daily dosing of SystaneTM Balance, patients were randomized to the respective treatment arm and dosed twice daily for 16-weeks. Main outcome measures The study was set up to explore efficacy on a number of sign and symptom endpoints including total and sub-region corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity and Ocular Surface Disease Index (OSDI©) questionnaire. Results CyclASol showed a consistent reduction in corneal and conjunctival staining compared to both vehicle and Restasis over the 16-week treatment period with an early onset of effect (at day 14). A mixed-effect-model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining p<0.1, central corneal staining p<0.001, conjunctival staining p<0.01). This model-based analysis suggests a significant CyclASol effect for OSDI© as symptom parameter (p<0.01). The number of ocular AEs were low in all treatment groups. Conclusions CyclASol® showed efficacy, safety and tolerability at two concentrations in moderate to severe DED. In a direct head to head against open-label RestasisTM, CyclASol® was found to have an earlier onset of action, as early as after two weeks of treatment in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.
Impact of vision loss on health-related quality of life in Trinidad and Tobago Ophthalmology (IF 7.479) Pub Date : 2019-01-28 T. Braithwaite, H. Bailey, D. Bartholomew, A. Saei, K. Pesudovs, S.S. Ramsewak, R. Bourne, A. Gray
Purpose To determine whether distance vision impairment (VI) (Logarithm of the Minimum Angle of Resolution (LogMAR) >0.30), or near VI (NVI) (LogMAR 0.32 to 1.30 at 40cm with <0.30 at 3m) independently predict health-related quality of life (HRQoL), and to estimate societal impact. Design The National Eye Survey of Trinidad and Tobago was a population-based, cross-sectional eye survey using multi-stage, cluster random sampling with probability-proportionate-to-size methods. Participants Adults aged > 40 years. Methods Responders rated general health level in the five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) of the EQ-5D 5-level instrument. Multivariable regression analysis with robust standard error estimation explored the relationship between utility score and presenting vision. Main Outcome Measures Utility value and Quality Adjusted Life Year (QALY) loss by vision category. Results 62.4% (2658/4263) adults completed the EQ-5D-5L. Mean age was 58.4 (SD 11.8, range 40 to 103) years and 56.3% were female. Blindness had the largest independent effect on utility coefficient, at -0.140 (95% CI -0.092 to -0.192), with mean utility value 0.727 (95% CI 0.671-0.784) and mean EQ-VAS score 69.9 (95% CI 62.0-77.8). Near VI was also independently associated with utility loss of -0.012 (95% CI -0.004 to -0.021). Independent predictors of utility<1.000 included female sex, older age, being uninsured, lower educational attainment, ethnicity, and multiple medical co-morbidities. A hypothetical person, experiencing onset of a stable vision state at 40 years, would be expected to accrue lifetime loss of 0.45 QALYs for near VI, 0.72 QALYs for mild VI, 1.64 QALYs for moderate VI, 3.30 QALYs for severe VI and 5.13 QALYs for blindness. VI caused 762.3 QALYs lost per 100,000 population per year, of which 36.5% were attributed to near VI, exceeding the equivalent QALY loss from stroke (307 QALYs), depression (284 QALYs), and arthritis (522 QALYs). 91% (694.9/762.3) of the VI-related QALY loss was potentially avoidable. Conclusions This is the first population-based survey to identify that both distance and near VI independently reduce HRQoL. The estimated QALY loss highlights the societal importance of efforts to address all degrees of avoidable VI.
Three-year Observation of Children Age 3 to 10 Years Old with Untreated Intermittent Exotropia Ophthalmology (IF 7.479) Pub Date : 2019-01-26 Brian G. Mohney, Susan A. Cotter, Danielle L. Chandler, Jonathan M. Holmes, David K. Wallace, Tomohiko Yamada, David B. Petersen, Raymond T. Kraker, Christie L. Morse, B.Michele Melia, Rui Wu,
Purpose To describe the course of intermittent exotropia (IXT) in children followed without treatment for three years Design Observation arm from randomized trial of short-term occlusion vs. observation Participants 183 children 3 to 10 years old with previously untreated IXT and 400 arcsec or better near stereoacuity Methods Participants were to receive no treatment unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, or 6-month intervals thereafter for 3 years Main Outcome Measures The primary outcome was deterioration by 3 years, defined as meeting motor criterion (constant XT ≥10 prism diopters (Δ) at distance and near) or near stereoacuity criterion (≥ 2 octaves decrease from best previous measure). For the primary analysis, participants also were counted as deteriorated if treatment was prescribed without meeting either deterioration criterion. Results The protocol-specified estimate of cumulative probability of deterioration by 3 years was 15% (95% CI = 10% to 22%), but it is likely an overestimate, partly due to misclassification. Among 25 deteriorations, 2 met motor deterioration, 11 met stereoacuity deterioration, and 12 started treatment without meeting either criteria (7 for social concern, 1 for diplopia, 4 for other reasons). Among the 132 participants who completed the 3-year visit and had not been treated during the study, only 1 (<1%) met motor or stereoacuity deterioration criteria at 3 years. Of the 4 participants completing the 3-year visit who met deterioration criteria previously and had not started treatment, none still met deterioration criteria. Between the baseline and 3-year exam for these 132, improvement occurred in distance and near stereoacuity (mean improvement = 0.14 and 0.14 log arcsec; P = <0.001 and <0.001, respectively), distance exotropia control (mean improvement = 0.6 points; P = <0.001), and distance exodeviation magnitude (mean improvement = 2.2Δ; P = 0.002). Conclusions Among children 3 to 10 years old with IXT and for whom surgery was not considered as the immediately-needed treatment, stereoacuity deterioration or progression to constant exotropia over 3 years was uncommon, and exotropia control, stereoacuity, and magnitude of deviation remained stable or improved slightly.
Plus Disease in the Telemedicine Approaches to Evaluating of Acute-Phase ROP (e-ROP) Study: Characteristics, Predictors and Accuracy of Image Grading Ophthalmology (IF 7.479) Pub Date : 2019-01-25 Qianqian Ellie Cheng, Ebenezer Daniel, Wei Pan, Agnieshka Baumritter, Graham E. Quinn, Gui-shuang Ying,
Purpose To describe characteristics and predictors of plus disease, and the accuracy of image grading for plus disease in the e-ROP Study. Design Secondary analyses of data from 13 North American centers. Participants Premature infants with birth weight (BW) <1251g. Methods Infants underwent regularly scheduled diagnostic exams by ophthalmologists and digital imaging by trained imagers using a wide-field digital camera. Two masked non-physician trained readers independently evaluated images for posterior pole abnormality (normal, preplus, plus) with discrepancies adjudicated by a reading supervisor. Logistic regression models were used to determine predictors for plus disease. The sensitivity and specificity of image grading for plus disease were calculated using the clinical exam finding as reference standard. Main Outcome Measures Odds ratios (OR), sensitivity and specificity. Results Among 1239 infants (mean BW 864g, mean gestational age (GA) 27 weeks), 129 (10%) infants (226 eyes, 75% bilateral) had plus disease from clinical examination. When plus disease was first diagnosed in clinical exam at median postmenstrual age (PMA) of 36 (range: 32-43) weeks, 94-96% of plus occurred in superior or inferior temporal quadrant. Significant predictors for plus disease from multivariate analysis were: GA (OR=3.2 for ≤24 vs. ≥28 weeks, p=0.004), race (OR=2.4 for White vs. Black, p=0.01), respiratory support (OR=7.1, p=0.006), weight gain (OR=1.5 for weight gain ≤12 vs. >18 g/day, p=0.03), and image findings at the first image session including: presence of preplus/plus disease (OR=2.7, p=0.003), ROP stage (OR=4.2 for stage 3 ROP vs. no ROP, p=0.006) and blot hemorrhage (OR=3.1, p=0.003). These features predicted plus disease with an area under ROC curve of 0.89 (95% CI: 0.85-0.92). The image grading using preplus as the cutpoint had sensitivity 94% (95% CI: 90-97%) and specificity 81% (95% CI: 79-82%) for detecting plus disease in an eye. Conclusions Among e-ROP infants, plus disease developed in 10% of infants at median PMA of 37 weeks, with majority being bilateral, and mostly in superior or inferior temporal quadrant. GA, race, respiratory support, postnatal weight gain, image findings of posterior pole and ROP predict development of plus disease. Non-physician image grading can detect almost all plus disease with good specificity.
Canadian Treat and Extend Analysis Trial with Ranibizumab in Patients with Neovascular Age-related Macular Disease: 1-Year Results of the Randomized CANTREAT Study Ophthalmology (IF 7.479) Pub Date : 2019-01-21 Peter J. Kertes, Ivan J. Galic, Mark Greve, R. Geoff Williams, Emmanouil Rampakakis, Andrea Scarino, Tom Sheidow
Objective To compare the efficacy of ranibizumab using a treat-and-extend (T&E) regimen to monthly dosing in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Design Prospective, randomized, open-label, multicenter, non-inferiority, post-authorization study. Participants Treatment-naïve patients with choroidal neovascularization secondary to AMD. Methods Subjects with nAMD were randomized 1:1 to receive intravitreal ranibizumab at a dose of 0.5 mg in either a T&E or monthly dosing regimen. The non-inferiority of T&E compared to the monthly dosing regimen was to be shown using a margin of 5 letters in best-corrected visual acuity (BCVA) improvement. Main Outcome Measures Mean change in BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) from Baseline to Month 12. Results Baseline and 12-month visual acuity data are available for 526 patients (T&E: n=268; monthly: n=258). At baseline mean (standard deviation [SD]) age was 78.8 (7.8) years, 60.3% were females, and 94.3% were Caucasian. No significant between-group baseline differences were observed. The primary outcome of non-inferiority regarding visual acuity was met with mean (SD) BCVA improvement of 8.4 (11.9) and 6.0 (11.9) letters (P=0.017), in the T&E and monthly regimens, respectively, with a between-group mean difference of 2.38 (95% CI: 0.32, 4.45). As per protocol, a secondary analysis was then performed to test for superiority of number of injections received up to Month 12. This analysis demonstrated significantly fewer injections with T&E vs monthly dosing (9.4 and 11.8, respectively), with a mean difference of -2.46 (95% CI: -2.68, -2.23). Conclusions The 12-month results of this 2-year study demonstrate that in regard to visual outcomes, the T&E regimen was non-inferior to a monthly dosing regimen. Similar visual outcomes in the T&E group as in the monthly dosing group were achieved with significantly fewer injections.
Changes in EHR use time and documentation over the course of a decade Ophthalmology (IF 7.479) Pub Date : 2019-01-18 Isaac H. Goldstein, Thomas Hwang, Sowjanya Gowrisankaran, Ryan Bales, Michael F. Chiang, Michelle R. Hribar
Objective With the current wide adoption of Electronic Health Records (EHRs) by ophthalmologists, there are widespread concerns about the amount of time spent using the EHR. The goal of this study was to examine how EHR use time as well as related documentation behaviors changed a decade after EHR adoption. Design Single center cohort study Subjects 685,361 office visits from 70 ophthalmology providers. Methods We calculated time spent on the EHR associated with each individual office visit using EHR audit logs, and determined chart closure times and progress note length from secondary EHR data. We tracked and modeled how these metrics changed from 2006 to 2016 with linear mixed models. Main Outcome Measures Minutes spent on the EHR associated with an office visit, chart closure time in hours from the office visit check-in time, and progress note length in characters. Results Median EHR time per office visit in 2006 was 4.2 (Interquartile range [IQR] 3.5) minutes, and increased to 6.4 (IQR 4.5) minutes in 2016. Median chart closure time was 2.8 (IQR 21.3) hours in 2006 and decreased to 2.3 (IQR 18.5) hours in 2016. In 2006, Median note length was 1,530 (IQR 1,435) characters, and increased to 3,838 (IQR 2,668.3) in 2016. Linear Mixed models found EHR time per office visit was 31.9 ± .2 % (p<.001) greater in 2014-2016 than in 2006-2010, chart closure time was 6.7 ± .3 hours (p<.001) shorter in 2014-2016 versus 2006-2010, and note length was 1807.4 ± 6.5 characters (p<.001) longer in 2014-2016 versus 2006-2010. Conclusions After a decade of use providers spend more time using the EHR for an office visit, generate longer notes, and close the chart faster. These changes are likely to represent increased time and documentation pressure for providers, and EHR redesign and new documentation regulations may help address these issues.
Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy Ophthalmology (IF 7.479) Pub Date : 2019-01-17 Sarah Mrejen, Chandrakumar Balaratnasingam, Talia R. Kaden, Alexander Bottini, Kunal Dansingani, Kavita V. Bhavsar, Nicolas A. Yannuzzi, Samir Patel, Kevin C. Chen, Suqin Yu, Guillaume Stoffels, Richard F. Spaide, K.Bailey Freund, Lawrence A. Yannuzzi
Purpose To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). Design Retrospective, longitudinal study Subjects One-hundred and thirty-three subjects (217 eyes) with chronic CSC. Methods A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF) and optical coherence tomography (OCT). Main Outcome Measures Best corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1, 5 and 10-year follow-up visits, and causes of vision loss at final visit. Results Data from 6,228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 males (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least one eye and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1 or 5-year follow-up visits (both p≥0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (p=0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization, outer retinal disruption on OCT and FAF changes were associated with poorer vision at final visit (all p≤0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (p=0.001). Conclusion Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.
Evolution in the Risk of Cataract Surgical Complications among Patients Exposed to Tamsulosin Ophthalmology (IF 7.479) Pub Date : 2019-01-14 Robert J. Campbell, Sherif R. El-Defrawy, Sudeep S. Gill, Marlo Whitehead, Erica de L.P. Campbell, Philip L. Hooper, Chaim M. Bell, Martin W. ten Hove
Purpose Tamsulosin is associated with intraoperative floppy iris syndrome (IFIS), an important risk factor for complications during cataract surgery. Significant efforts have been made to increase awareness of the risks associated with tamsulosin, and educational initiatives have fostered the uptake of technical adjustments to decrease adverse event rates among tamsulosin-exposed patients. However, the effectiveness of these efforts at the population level has not been studied. Design Population-based study to evaluate cataract surgical adverse event rates over time among patients exposed to tamsulosin and those not exposed to this drug. Participants All male patients 66 years of age and older undergoing cataract surgery in Ontario, Canada, between January 1, 2003, and December 31, 2013, were included in the study. Methods Linked healthcare databases were used to study the evolution in the risk of cataract surgical adverse events over time among tamsulosin-exposed and non–tamsulosin-exposed patients adjusting for patient-, surgeon-, and institution-level covariates. The study timeframe incorporated periods before and after the first reports of tamsulosin-associated IFIS. Main Outcome Measures Four important cataract surgical adverse events were evaluated: posterior capsule rupture, dropped lens fragments, retinal detachment, and suspected endophthalmitis. Results Among patients exposed to tamsulosin, the risk of surgical adverse events decreased over time (odds ratio, 0.95 per year; 95% confidence interval, 0.91–0.99 per year). This trend was observed across patient age strata. Among patients not recently exposed to tamsulosin, the risk of surgical adverse events also decreased over time (odds ratio, 0.96 per year; 95% confidence interval, 0.95–0.98 per year). Conclusions The risk of cataract surgical complications among both tamsulosin-exposed and non–tamsulosin-exposed patients declined between 2003 and 2013. Tamsulosin remains an important risk factor for cataract surgical adverse events, and ongoing efforts will be needed to develop and disseminate surgical approaches that mitigate the risks posed by tamsulosin.
The Oculome panel test: next-generation sequencing to diagnose a diverse range of genetic developmental eye disorders Ophthalmology (IF 7.479) Pub Date : 2019-01-14 Aara Patel, Jane D. Hayward, Vijay Tailor, Rodney Nyanhete, Helena Ahlfors, Camila Gabriel, Tommaso B. Jannini, Yassir Abbou-Rayyah, Robert Henderson, Ken K. Nischal, Lily Islam, Maria Bitner-Glindzicz, Jane Hurst, Leonardo E. Valdivia, Mario Zanolli, Mariya Moosajee, John Brookes, Maria Papadopoulos, Jane C. Sowden
Purpose To develop a comprehensive next-generation sequencing panel assay which screens genes known to cause developmental eye disorders and inherited eye disease (Oculome test) and to evaluate its diagnostic yield in a paediatric cohort with malformations of the globe, anterior segment anomalies and/or childhood glaucoma. Design Evaluation of diagnostic test. Participants 277 children age 0-16 years diagnosed with nonsyndromic or syndromic developmental eye defects without a genetic diagnosis. Methods We developed a new Oculome panel using a custom-designed Agilent SureSelect QXT target capture method to capture and perform parallel high through put sequencing analysis of 429 genes associated with eye disorders. We confirmed suspected pathogenic variants by bidirectional Sanger sequencing. Main outcome measures We collated clinical details and the oculome molecular genetic results. Results The Oculome design covers 429 known eye disease genes; these are subdivided into 5 overlapping virtual sub-panels for anterior segment developmental anomalies and glaucoma (ASDA; 59 genes), microphthalmia-anophthalmia-coloboma (MAC; 86 genes), congenital cataracts and lens-associated conditions (CAT; 70 genes), retinal dystrophies (RET; 235 genes), and albinism (15 genes), and as well as additional genes implicated in optic atrophy and complex strabismus (10 genes). Panel development and testing included analysing n = 277 clinical samples and 3 positive control samples using Illumina sequencing platforms; >30 X read-depth was achieved for 99.5% of the targeted 1.77 Mb region. Bioinformatics analysis performed using a pipeline based on Freebayes and ExomeDepth to identify coding sequence and copy number variants respectively, resulted in a definitive diagnosis in 68 / 277 cases with variability in diagnostic yield between phenotypic sub-groups; MAC: 8.2% (8 of 98 cases solved), ASDA: 24.8% (28 of 113 cases solved), other / syndromic 37.5% (3 of 8 cases solved); RET: 42.8% (21 of 49 cases solved); CAT: 88.9% (8 of 9 cases solved). Conclusion The Oculome test diagnoses a comprehensive range of genetic conditions affecting the development of the eye, potentially replacing protracted and costly multidisciplinary assessments and allowing for faster targeted management. The Oculome enabled the molecular diagnosis of a significant number of cases in our sample cohort of varied ocular birth defects.
Simulating an Anti–Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration: A HARBOR Subanalysis Ophthalmology (IF 7.479) Pub Date : 2019-01-11 Marco Zarbin, Min Tsuboi, Lauren F. Hill, Ivaylo Stoilov
Objective A simulated switching study assessed the effects of continuing the same anti–vascular endothelial growth factor (VEGF) treatment among patients who are typically considered for a therapy switch. Post hoc analysis of data from HARBOR (NCT00891735) was undertaken. Patients with neovascular age-related macular degeneration who demonstrated a suboptimal response after 3 or 6 months of ranibizumab treatment were identified as switching candidates. Rather than switching, however, patients continued on ranibizumab treatment, and visual/anatomic outcomes from the timepoint of “hypothetical switch” were examined. Design Post hoc analysis of the phase 3 HARBOR clinical trial. Subjects Patients were included in 3- and 6-month “switcher” analyses if they received 3/3 initial monthly ranibizumab doses and 5/6 initial monthly ranibizumab doses, respectively, and met all the following: ≤ 5-letter gain from baseline, best-corrected visual acuity (BCVA) 20/40 or worse, intraretinal or subretinal fluid with central foveal thickness (CFT) ≥ central subfield thickness. Methods Patient data were examined at months 3 and 6 to identify those who met predetermined switching criteria. BCVA and CFT were examined from the point at which switching criteria were met through months 6, 12, 18, and 24 of HARBOR and compared with those who did not meet the criteria. Main Outcome Measures Outcome measures included mean BCVA and CFT change over time from the point (month 3 or 6) at which switching criteria were met. Results By months 3 and 6, only 44 of 1059 (4.2%) and 37 of 769 (4.8%) patients, respectively, met the inclusion criteria for hypothetical switching. Patients who met switching criteria at month 3 gained, on average, 5.3 letters from months 3 to 12 and 2.7 letters from months 3 to 24. Month 6 switchers gained, on average, 1.6 letters from months 6 to 12 and 1.8 letters from months 6 to 24. Both groups experienced significant CFT reductions over 24 months. Conclusion Month 3 hypothetical switchers achieved vision and anatomic improvement while remaining on their original ranibizumab treatment. Month 6 switcher outcomes replicated those commonly reported in published anti-VEGF switching studies: stable vision or nominal improvements in vision with continued substantial anatomic improvement.
A Randomized Clinical Trial Of Immediate versus Delayed Spectacles for Moderate Hyperopia in 1- and 2-Year-Olds Ophthalmology (IF 7.479) Pub Date : 2019-01-04 Marjean T. Kulp, Jonathan M. Holmes, Trevano W. Dean, Donny W. Suh, Raymond T. Kraker, David K. Wallace, David B. Petersen, Susan A. Cotter, Ruth E. Manny, Rosanne Superstein, Tawna L. Roberts, John M. Avallone, Deborah R. Fishman, S. Ayse Erzurum, David Leske, Alex Christoff,
Objective Two strategies were compared for managing moderate hyperopia without manifest strabismus among 1- and 2-year-old children: 1) immediate prescription of glasses vs 2) observation without glasses unless reduced distance visual acuity (VA), reduced stereoacuity, or manifest strabismus. Design Prospective randomized clinical trial Participants 130 children 1 to 2 years old with hyperopia between +3.00 diopters (D) and +6.00D spherical equivalent (SE) in at least one eye, anisometropia ≤1.50D SE and astigmatism ≤1.50D based on cycloplegic refraction, and no manifest strabismus. Methods Participants were randomly assigned to glasses (1.00D less than full cycloplegic hyperopia) versus observation and followed every 6 months for 3 years. Glasses were prescribed to those assigned to observation if they met pre-specified deterioration criteria of distance VA or near stereoacuity below age norms, or development of manifest strabismus. Main Outcome Measure At the 3-year primary outcome examination, participants were classified as failing the randomized management regimen if distance VA or stereoacuity were below age norms, or manifest strabismus was observed (each with and without correction in trial frames, confirmed by masked retest, irrespective of whether deterioration had occurred previously), or if strabismus surgery had been performed. Results Of the 106 (82%) participants completing the 3-year primary outcome examination, failure occurred in 11 (21%) of 53 in the glasses group and 18 (34%) of 53 in the observation group (difference = -13%; 95% CI = -31% to 4%; p=0.14). The reasons for failure in the glasses and observation groups were reduced stereoacuity in 6 (11%) and 16 (30%) respectively, reduced VA in 3 (6%) and 4 (8%), and manifest strabismus in 5 (9%) in each group. Fifty-eight percent (95% CI = 46% to 70%) in the observation group, and 33% (95% CI = 22% to 46%) in the glasses group met deterioration criteria (requiring glasses if not wearing). Conclusion For 1- and 2-year-olds with uncorrected moderate hyperopia (+3.00D to +6.00D SE), our estimates of failure, after 3 years of 6-monthly follow-up, are inconclusive, and consistent with either a small to moderate benefit or no benefit of immediate prescription of glasses compared with careful observation (with glasses only if deteriorated).
Factors Associated with Progression of Japanese Open-Angle Glaucoma with Lower Normal Intraocular Pressure Ophthalmology (IF 7.479) Pub Date : 2018-12-31 Rei Sakata, Takeshi Yoshitomi, Aiko Iwase, Chota Matsumoto, Tomomi Higashide, Motohiro Shirakashi, Makoto Aihara, Kazuhisa Sugiyama, Makoto Araie,
Purpose To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. Design Prospective 5-year study. Participants Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. Methods Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. Main Outcome Measures Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. Results We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], −2.8 decibels [dB]). The MD slope averaged −0.33 dB/year (median, −0.23; 95% confidence interval [CI], −0.44 to −0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55–78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37–60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38–71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. Conclusions In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was –0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression. Supplementary material available at www.aaojournal.org.
Calculation of axial length using a single group refractive index versus using different refractive indices for each ocular segment: theoretical study and refractive outcomes Ophthalmology (IF 7.479) Pub Date : 2018-12-31 Li Wang, Danmin Cao, Mitchell P. Weikert, Douglas D. Koch
Purpose To investigate the difference between the segmented axial length (AL) and the displayed AL on an optical low-coherence reflectometry (OLCR) biometer (Part I) and to compare the refractive prediction errors calculated using the segmented and displayed ALs (Part II). Design Retrospective case series. Participants 4992 eyes from 4992 subjects in Part I and 1758 eyes from 1758 subjects in Part II. Methods In Part I, we calculated the segmented AL as the sum of geometrical ocular segments converted from the optical path length (OPL) in each medium. To convert the OPL to a geometrical distance in each medium, we used four sets of group refractive indices. In Part II, the mean absolute prediction error (MAE) was calculated with the displayed AL and segmented AL using 6 intraocular lens power formulas: Olsen, Barrett Universal II (Barrett), Haigis, Hoffer Q, Holladay 1, and SRK/T. Main outcome measures Segmented AL, difference in AL (segmented AL - displayed AL), MAE, and percentage of eyes within 0.5 D of error. Results The segmented ALs were up to 0.29 mm longer in short eyes and 0.50 mm shorter in long eyes. The differences in ALs were negatively correlated with the displayed ALs (r values -0.941 to -0.913, P<0.001). MAEs were significantly lower using segmented ALs for all formulas except the Olsen in both the group as a whole and in the long eye subgroup (AL≥26 mm) and for the Holladay 1 and Hoffer Q in short eye subgroup (AL≤ 22 mm). Use of segmented ALs produced a greater percentage of eyes within 0.5 D of error for all formulas except the Olsen and Haigis for both the group as a whole and for long eyes and for the Holladay 1 in short eyes. Conclusion The segmented ALs were longer in short eyes and shorter in long eyes compared to the displayed ALs calculated with a single group refractive index for the whole eye. The refractive accuracy with segmented ALs was improved in short eyes with the Hoffer Q and Holladay 1 and in long eyes with all formulas except the Olsen formula.
A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study Ophthalmology (IF 7.479) Pub Date : 2018-12-27 Andrea Leonardi, Serge Doan, Mourad Amrane, Dahlia Ismail, Jesús Montero, János Németh, Pasquale Aragona, Dominique Bremond-Gignac,
Background Vernal keratoconjunctivitis (VKC) is a chronic, allergic, and potentially severe ocular disease affecting children and adolescents that can lead to impaired quality of life (QoL) and loss of vision. Purpose This study evaluated the efficacy and safety of an investigational therapy for severe VKC, cyclosporine A cationic emulsion (CsA CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations. Design VEKTIS is a phase 3, multicenter, double-masked, vehicle-controlled trial. Participants Pediatric patients (4-18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale). Methods 169 patients were randomized to CsA CE 0.1% (1 mg/mL) eye drops four times daily (QID, high-dose), CsA CE twice daily (BID, low-dose) + vehicle BID, or vehicle QID for 4 months. Main Outcome Measures The primary endpoint was a mean composite score that reflected CFS, rescue medication use (dexamethasone 0.1% QID), and corneal ulceration over the 4 months. Results Differences in least-squares means versus vehicle for the primary endpoint were statistically significant for both the high-dose (0.76, P=0.007) and the low-dose group (0.67, P=0.010), with treatment effect mainly driven by CFS score. Significant differences were found between both active treatment groups and vehicle for use of rescue medication. VKC symptoms and patient QoL (assessed by visual analogue scale and the Quality of Life in Children with Vernal Keratoconjunctivitis [QUICK] questionnaire) improved in all 3 groups, with significant improvements for high-dose CsA CE versus vehicle. Conclusions The efficacy of high-dose CsA CE in improving keratitis, symptoms, and QoL for those with severe VKC was demonstrated in these study patients. In addition, in this study cohort, CsA CE was well-tolerated.
Lamina cribrosa morphology in glaucomatous eyes with hemifield defect in a Korean population Ophthalmology (IF 7.479) Pub Date : 2018-12-24 Ji-Ah Kim, Tae-Woo Kim, Eun Ji Lee, Michael J.A Girard, Jean Martial Mari
Purpose To compare regional variations in lamina cribrosa (LC) curvature and depth between healthy eyes (Group 1) and naïve eyes with primary open-angle glaucoma (POAG) having superior (Group 2), inferior (Group 3), and both (Group 4) hemifield retinal nerve fiber layer (RNFL) defects. Design Cross-sectional study Participants Each group consisted of 39 eyes of 39 Korean patients who were matched for age, sex, and axial length. Methods The LC curvature index (LCCI) and LC depth (LCD) were measured in B-scan images obtained using enhanced depth imaging optical coherence tomography at seven locations spaced equidistantly across the vertical optic disc diameter. Superior and inferior LCCI and LCD were compared by calculating the superior-to-inferior ratios (Sup/Inf ratio). Main Outcome Measures Comparisons of LCCI, LCD, and Sup/Inf ratio among the four groups. Results Compared with healthy eyes (group 1), LCCIs were larger at the superior and middle planes in group 2, at the inferior and middle planes in group 3, and at all planes in group 4 (P ≤ 0.004). LCD showed similar results, but there was no difference in superior planes between groups 1 and 2. The Sup/Inf ratio of LCCI differed significantly between groups 1 (1.03) and 2 (1.20), groups 1 and 3 (0.79), groups 2 and 3, groups 2 and 4 (0.96), and groups 3 and 4 (all P < 0.001), but not between groups 1 and 4 (P = 0.273). The Sup/Inf ratio of LCD differed only between groups 2 and 3 (P = 0.002). Conclusions Eyes with POAG showed regional differences in LC morphology, corresponding with the location of RNFL defects. The regional variations in LCCI suggest that LC morphology in POAG would be better assessed on a regional basis than by a global index.
From Machine to Machine: An OCT-trained Deep Learning Algorithm for Objective Quantification of Glaucomatous Damage in Fundus Photographs Ophthalmology (IF 7.479) Pub Date : 2018-12-20 Felipe A. Medeiros, Alessandro A. Jammal, Atalie C. Thompson
Purpose Previous approaches using deep learning algorithms to classify glaucomatous damage on fundus photographs have been limited by the requirement for human labeling of a reference training set. We propose a new approach using quantitative spectral-domain optical coherence tomography (SDOCT) data to train a deep learning algorithm to quantify glaucomatous structural damage on optic disc photographs. Design : Cross-sectional study Participants : 32,820 pairs of optic disc photos and SDOCT retinal nerve fiber layer (RNFL) scans from 2,312 eyes of 1,198 subjects. Methods The sample was randomly divided into validation plus training (80%) and test (20%) sets, with randomization performed at the patient level. A deep learning convolutional neural network was trained to assess optic disc photographs and predict SDOCT average RNFL thickness. Main Outcome Measures The performance of the deep learning algorithm was evaluated in the test sample by evaluating correlation and agreement between the predictions and actual SDOCT measurements. We also assessed the ability to discriminate eyes with glaucomatous visual field loss from healthy eyes with the area under the receiver operating characteristic curve (ROC). Results : The mean prediction of average RNFL thickness from all 6,292 optic disc photos in the test set was 83.3 ± 14.5 μm, whereas the mean average RNFL thickness from all corresponding SDOCT scans was 82.5 ± 16.8 μm (P = 0.164). There was a very strong correlation between predicted and observed RNFL thickness values (Pearson’s r = 0.832; R2 = 69.3%; P<0.001), with mean absolute error (MAE) of the predictions of 7.39 μm. The areas under the ROC curves for discriminating glaucomatous from healthy eyes with the deep learning predictions and actual SDOCT average RNFL thickness measurements were 0.944 (95% CI: 0.912– 0.966) and 0.940 (95% CI: 0.902 – 0.966), respectively (P = 0.724). Conclusion We introduced a novel deep learning approach to assess fundus photographs and provide quantitative information about the amount of neural damage that can be used to diagnose and stage glaucoma. In addition, training neural networks to objectively predict SDOCT data represents a new approach that overcomes limitations of human labeling and could be useful in other areas of ophthalmology.
Temporal Raphe Sign for Discrimination of Glaucoma from Optic Neuropathy in Eyes with Macular Ganglion Cell-Inner Plexiform Layer Thinning Ophthalmology (IF 7.479) Pub Date : 2018-12-18 Jinho Lee, Young Kook Kim, Ahnul Ha, Yong Woo Kim, Sung Uk Baek, Jin-Soo Kim, Haeng Jin Lee, Dai Woo Kim, Jin Wook Jeoung, Seong-Joon Kim, Ki Ho Park
Purpose To evaluate the potential of the temporal raphe sign on the macular ganglion cell-inner plexiform layer (mGCIPL) thickness map for discriminating glaucomatous from non-glaucomatous optic neuropathy in eyes with mGCIPL thinning. Design Cross-sectional study. Participants One-hundred and seventy-five eyes of 175 patients with mGCIPL thinning on Cirrus high-definition optical coherence tomography (OCT) were retrospectively included. Glaucoma specialists and neuro-ophthalmology specialists evaluated the patients’ medical records for diagnosis of glaucomatous or non-glaucomatous optic neuropathy. Finally, by consensus, 67 eyes with glaucomatous optic neuropathy (GON) and 73 eyes with non-glaucomatous optic neuropathy (NGON) were enrolled. Methods A positive temporal raphe sign was declared in cases where there was a straight line longer than one-half of the length between the inner and outer annulus in the temporal elliptical area of the mGCIPL thickness map. Decision tree analysis was performed in order to formulate a diagnostic model. Main Outcome Measures Areas under receiver operating characteristics curve (AUC) with sensitivity and specificity. Results The temporal raphe sign was observed in 61 of 67 GON eyes (91.0%), but only in 21 of 73 NGON eyes (28.8%) (P < 0.001; chi-square test). On this basis, the diagnostic ability of the temporal raphe sign for discriminating GON from NGON was judged to be good (AUC 0.811 [95% CI, 0.749-0.874]; sensitivity 91.0%; specificity 71.2%). The diagnostic performance of the decision-tree-based model (AUC 0.879 [95% CI, 0.824-0.933]; sensitivity 88.1%; specificity 87.7%) was better than that of either the temporal raphe sign or the relative afferent pupillary defect (RAPD) alone (P = 0.005, P < 0.001, respectively; DeLong’s test). The decision tree model revealed the following: (1) if the temporal raphe sign is positive and the RAPD is absent, the case should be diagnosed as GON; (2) if the temporal raphe sign is absent regardless of the presence or absence of the RAPD, or both the temporal raphe sign and the RAPD are present, the case should be diagnosed as NGON. Conclusion In clinical practice, determining whether the temporal raphe sign appears on OCT macular scans can be a useful tool for discrimination of glaucomatous from non-glaucomatous mGCIPL thinning.
The Associations between Near Visual Activity and Incident Myopia in Children 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.
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.
Outcomes of Eyes Lost to Follow-up with Proliferative Diabetic Retinopathy That Received Panretinal Photocoagulation versus 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 more than 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 more than 6 months after treatment were identified. Visual acuity (VA) and anatomic outcomes at the visit before being 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 2 treatment groups. Main Outcomes Measures Visual acuity 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 anti-VEGF group, mean VA worsened significantly when comparing the visit before being LTFU (0.43±0.38 logarithm of the minimum angle of resolution [logMAR]) with the return visit (0.97±0.80 logMAR; P = 0.001) as well as with the final visit (0.92±0.94 logMAR; P = 0.01). In the PRP group, mean VA worsened significantly when comparing the visit before being LTFU (0.42±0.34 logMAR) with the return visit (0.62±0.64 logMAR; P = 0.03). However, no significant difference was observed at the final visit (0.46±0.47 logMAR; P = 0.38). There was a significantly greater number of eyes with tractional retinal detachment in the IVI group compared with the PRP group at the final visit (10 vs. 1, respectively; P = 0.005). There was a significantly greater incidence of neovascularization of the iris in the IVI arm compared with the PRP arm at the final visit (4 vs. 0, respectively; P = 0.02). Conclusions Eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after being LTFU compared with eyes that received PRP. Given the potential sequelae of being LTFU, the choice of treatment for PDR must be considered carefully.
Spectral-Domain OCT Measurements in Alzheimer’s Disease 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 C.T. Mok, Carol Y. Cheung
Topic OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (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 Relevance Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD. Methods We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that 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 fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality. Results We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed 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 range, –0.52 to –0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, –0.67; 95% CI, –0.95 to –0.38; I2 = 89%) and choroidal thickness (SMD range, –0.88 to –1.03; all P < 0.001) also were thinner in AD patients. Conclusions Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD.
Mediterranean Diet and Incidence of Advanced Age-Related Macular Degeneration Ophthalmology (IF 7.479) Pub Date : 2018-08-13 Bénédicte M.J. 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
Purpose To investigate associations of adherence to the Mediterranean diet (MeDi) with incidence of advanced age-related macular degeneration (AMD; the symptomatic form of AMD) in 2 European population-based prospective cohorts. Design Prospective cohort study of the Rotterdam Study I (RS-I) and the Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study populations. Participants Four thousand four hundred forty-six participants 55 years of age or older from the RS-I (The Netherlands) and 550 French adults 73 years of age or older from the 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 (1990–2011) in RS-I and every 2 years over a 4-year period (2006–2012) in the 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 4996 included participants, 155 demonstrated advanced incident AMD (117 from the RS-I and 38 from the Alienor Study). The mean follow-up time was 9.9 years (range, 0.6–21.7 years) in the RS-I and 4.1 years (range, 2.5–5.0 years) in the Alienor Study. Pooling data for both the RS-I and Alienor Study, participants with a high (range, 6–9) MeDi score showed a significantly reduced risk for incident advanced AMD compared with participants with a low (range, 0–3) MeDi score in the fully adjusted Cox model (hazard ratio, 0.59; 95% confidence interval, 0.37–0.95; P = 0.04 for trend). Conclusions Pooling data from the RS-I and Alienor Study, 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.
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 2 devices, the Compass (CMP, CenterVue, Padova, Italy) fundus perimeter and the Humphrey Field Analyzer (HFA, Zeiss, Dublin, CA), in detecting glaucomatous optic neuropathy (GON). Design Multicenter, cross-sectional, case-control study. Participants We sequentially enrolled 499 patients with glaucoma and 444 normal subjects to analyze relative precision. A separate group of 44 patients with glaucoma and 54 normal subjects was analyzed to assess test–retest variability. Methods One eye of recruited subjects was tested with the index tests: HFA (Swedish interactive thresholding algorithm [SITA] standard strategy) and CMP (Zippy Estimation by Sequential Testing [ZEST] strategy), 24-2 grid. The reference test for GON was specialist evaluation of fundus photographs or OCT, independent of the visual field (VF). 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. The 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 (pROC) curves and partial area under the curve (pAUC) to compare the diagnostic precision of the devices. Pointwise mean absolute deviation 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 decibels (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 with HFA in participants with glaucoma and by 49% in normal participants. Mean absolute deviation was similar, with no significant differences. Conclusions Relative diagnostic precision of the 2 devices is equivalent. Test–retest variability of MS for CMP was better than for HFA.
Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration Ophthalmology (IF 7.479) Pub Date : 2018-08-22 Jeannette J. Yu, Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew
Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P < 0.001); 67% of eyes progressed to late AMD 5 years after DPED detection. Drusenoid pigment epithelial detachment was associated with increased risk of ≥3 lines of VA loss (HR, 3.08; CI, 2.41–3.93; P < 0.001) with 46% of eyes experiencing vision loss at 5 years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR, 2.72, CI, 1.58–4.70; 2 vs. 0: HR, 3.16, CI, 1.60–6.21, P < 0.001) and increasing GRS group (4 vs. 1) (HR, 12.17, CI, 3.66–40.45, P < 0.001) were significantly associated with DPED development in AREDS. There were no significant genetic results in AREDS2. Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.
Efficacy of Topical Miltefosine in patients with Acanthamoeba Keratitis: A Pilot Study Ophthalmology (IF 7.479) Pub Date : 2018-12-17 Bhupesh Bagga, Joveeta Joseph, Prashant Garg, Kavya chandran, Priyanka Jayabhasker, Kodiganti Manjulatha, Savitri sharma
Miltefosine has been approved recently for Acanthamoeba keratitis (AK) after its successful use in animal model. This Pilot study is the first report of the efficacy of topical formulation of miltefosine in human subjects.
Oxidized Low-Density Lipoprotein and the Incidence of Age-related Macular Degeneration Ophthalmology (IF 7.479) Pub Date : 2018-12-17 Ronald Klein, Kristine E. Lee, Michael Y. Tsai, Karen J. Cruickshanks, Ronald E. Gangnon, Barbara E.K. Klein
Purpose To examine the relationship between serum oxidized low-density lipoprotein (ox-LDL) cholesterol and the incidence of age-related macular degeneration (AMD) over a 25-year period in a sample of persons from the population-based Beaver Dam Eye Study (BDES). Design Observational prospective cohort study. Participants A total of 4,972 people from the BDES (aged 43 to 84 and living in Beaver Dam, Wisconsin in 1988) seen during at least one of six examination phases at approximately 5-year intervals between 1988 and 2016. Methods A 50% random sample of participants (N=2,468) was selected for ox-LDL measurements. Stored frozen specimens from every exam phase were processed using an ELISA assay from a single batch. All available intervals were included for a person, resulting in 6,586 person-visits. Main Outcome Measures AMD was assessed using the Wisconsin Age-related Maculopathy Grading System and severity was defined using a 5-step severity scale. The severity of the worse eye at each examination was used for analyses. A Multi-State Markov (MSM) model was fit to simultaneously assess the ox-LDL relationship to all AMD transitions including incidence of any AMD, incidence of late AMD, and worsening and improvement of AMD over the 25 years of the study. Results The mean (SD) level of ox-LDL was 75.3 (23.1) U/L at the baseline examination. While adjusting for age, sex, ARMS2 and CFH risk alleles, and examination phase, the ox-LDL at the beginning of a period was not statistically significantly associated with the incidence of any AMD (Hazard Ratio (HR) per 10 U/L ox-LDL was 1.03, 95% Confidence Interval (CI) 0.98,1.09). Further, ox-LDL was not associated with worsening anywhere along the AMD severity scale nor incidence of late AMD. The lack of relationships of ox-LDL to the incidence of any AMD or worsening of AMD remained after adjustment for history of statin use, smoking status, body mass index, and history of cardiovascular disease (data not shown). Conclusions Our findings do not provide evidence for statistically significant relationships between ox-LDL and AMD disease development or worsening of AMD.
Clinical registries in ophthalmology Ophthalmology (IF 7.479) Pub Date : 2018-12-17 Jeremy C.K. Tan, Alexander C. Ferdi, Mark C. Gillies, Stephanie L. Watson
Topic Clinical registries in Ophthalmology Clinical relevance In recent years advancements in digital technology and increasing use of the electronic medical record in health systems have led to the dramatic growth in large clinical data sets. Clinical data registries are organised systems which collect data on patients diagnosed with a disease or condition, or who undergo a certain procedure. Methods A search of the PUBMED database was conducted in January 2018 for clinical registries in ophthalmology. Results 97 clinical eye registries were found, with significant growth in numbers in the last four decades. The most common conditions captured were blindness/low-vision, corneal transplantation, glaucoma and cataract surgery. The majority of registries originate in the European region, North America, and Australia. Nine registries had multinational coverage, while 48 were national registries. As the numbers and scope of clinical registries have expanded, valuable observational data have been used to study real-world clinical outcomes, in healthcare quality measurement and improvement, and to develop new guidelines and standards. Pertinent areas of its use include studying treatments and outcomes in cataract surgery, corneal transplantation and macular degeneration. Conclusions The use of clinical registries for quality improvement and research has grown significantly in the last few decades, and this trend will continue as information technology infrastructures develop.
Using a deep learning algorithm and integrated gradients explanation to assist grading for diabetic retinopathy Ophthalmology (IF 7.479) Pub Date : 2018-12-13 Rory Sayres, Ankur Taly, Ehsan Rahimy, Katy Blumer, David Coz, Naama Hammel, Jonathan Krause, Arunachalam Narayanaswamy, Zahra Rastegar, Derek Wu, Shawn Xu, Scott Barb, Anthony Joseph, Michael Shumski, Jesse Smith, Arjun B. Sood, Greg S. Corrado, Lily Peng, Dale R. Webster
Objective To understand the impact of deep learning diabetic retinopathy (DR) algorithms on physician readers in computer-assisted settings. Design Evaluation of diagnostic technology Participants 1,796 retinal fundus images from 1,612 diabetic patients. Methods 10 ophthalmologists (5 general ophthalmologists, 4 retina specialists, 1 retina fellow) read images for DR severity based on the International Clinical Diabetic Retinopathy disease severity scale in one of 3 conditions: Unassisted, Grades Only, or Grades + Heatmap. For Grades Only assistance, we surfaced a histogram of DR predictions (“grades”) from a trained deep-learning model. For Grades + Heatmap, we additionally showed explanatory heatmaps. Main Outcome Measures For each experiment arm we computed sensitivity and specificity of each reader and the model for different levels of DR severity against an adjudicated reference standard. We also measured accuracy (exact 5-class level agreement and Cohen’s quadratically-weighted kappa); reader-reported confidence (5-point Likert scale); and time on task. Results Readers graded more accurately with model assistance than without for the Grades Only condition (p < 0.001). Grades + Heatmaps improved accuracy for cases with DR (p < 0.001), but reduced accuracy for cases without DR (p = 0.006). Both forms of assistance increased readers’ sensitivity (For Moderate NPDR or worse, Unassisted: mean 79.4% [72.3, 86.5]; Grades Only: 87.5% [85.1, 89.9]; Grades + Heatmap: 88.7% [84.9, 92.5]) without a corresponding drop in specificity (Unassisted: 96.6% [95.9, 97.4]; Grades Only: 96.1% [95.5, 96.7], Grades + Heatmap: 95.5% [94.8, 96.1]). Model assistance increased the accuracy of retina specialists above that of the unassisted reader or model alone. Model assistance increased grading confidence and time on task. For most cases, Grades + Heatmap was only as effective as Grades Only. Over the course of the experiment, time on task decreased across all conditions, although most sharply for Grades + Heatmap. Conclusions Deep learning algorithms can improve the accuracy of, and confidence in, DR diagnosis in an assisted read setting. They also may increase time on task, although these effects may be ameliorated with experience.
Risk Factors for Severe Dry Eye Disease: Crowdsourced Research Using DryEyeRhythm Ophthalmology (IF 7.479) Pub Date : 2018-12-11 Takenori Inomata, Masahiro Nakamura, Masao Iwagami, Tina Shiang, Yusuke Yoshimura, Keiichi Fujimoto, Yuichi Okumura, Atsuko Eguchi, Nanami Iwata, Maria Miura, Satoshi Hori, Yoshimune Hiratsuka, Miki Uchino, Kazuo Tsubota, Reza Dana, Akira Murakami
This large-scale crowdsourced study using the iPhone application DryEyeRhythm identified the risk factors for severe dry eye disease-type symptoms, which included female sex, collagen disease, hay fever, depression, current contact-lens use, extended screen time, and smoking.
GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas Ophthalmology (IF 7.479) Pub Date : 2018-12-08 J.H. Francis, T. Milman, H. Grossniklaus, D.M. Albert, R. Folberg, G.M. Levitin, S.E. Coupland, F. Catalanotti, D. Rabady, C. Kandoth, K.J. Busam, D.H. Abramson
Purpose GNAQ mutations have been identified in port wine stains (both syndromic and non-syndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse- (those associated with Sturge-Weber syndrome (SWS)) and solitary choroidal hemangiomas. Participants Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), choroidal nevus (n =1) Methods Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in one specimen. Main outcomes Detection of GNAQ codon-specific mutation Results Activating somatic GNAQ mutations (c.547C>T; p.Arg183Cys) were found in 100% (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A>T;p.Gln209Leu) were found in 100% (6 of 6) of the solitary choroidal hemangiomas and (c.626A>C;p.Gln209Pro) in the choroidal nevus. Conclusion GNAQ mutations occur in both diffuse and solitary hemangiomas, although, at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge-Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.
Characterisation of poor visual outcomes of neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor agents Ophthalmology (IF 7.479) Pub Date : 2018-12-06 Chu Luan Nguyen, Mark C. Gillies, Vuong Nguyen, Vincent Daien, Amy Cohn, Gayatri Banerjee, Jennifer Arnold,
Purpose To investigate the incidence, characteristics and baseline predictors of poor visual outcomes in eyes with neovascular age-related macular degeneration (nAMD) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in daily clinical practice. Design Observational study. Participants Treatment-naïve eyes starting anti-VEGF therapy for nAMD between 2007 and 2012 tracked in the Fight Retinal Blindness! registry. Cases had sustained ≥15 letters of loss from baseline without recovery of visual acuity (VA) at final endpoint. A subgroup analysis included eyes that sustained ≥30 letters of loss. Controls had not sustained ≥15 letters of loss. Methods Kaplan-Meier curves estimated time to first development of loss of ≥15 letters. Cox-proportional hazards models evaluated predictors of loss of ≥15 letters. Main Outcome Measures The proportion of eyes with sustained VA loss within 5 years, the time to development of sustained VA loss and baseline predictors of sustained VA loss. Results There were 1760 eyes in total and 856 eyes that completed 5 years follow-up. The proportion of eyes with sustained VA loss of ≥15 letters at 5 years was 22.9% (95%CI, 20.7-25.1) and VA loss of ≥30 letters was 10.8% (95%CI, 9.1-12.5). Factors independently associated with higher incidence of sustained ≥15 letter loss included age >80 years (odds ratio [OR], 1.33 for patients >80 years vs. ≤80 years; 95%CI, 1.05-1.69; P =.02), fewer injections (OR, 0.97 per injection; 95%CI, 0.96-0.98; P=.0005) and more visits at which the choroidal neovascularisation was graded as active (OR, 1.97 for eyes in upper quartile of active visits vs. eyes in lowest quartile of active visits; 95%CI, 1.39-2.79; P=.0001). Baseline VA≥70 letters was associated with reduced risk of sustained ≥30 letter loss (OR, 0.61; 95%CI, 0.38-0.98; P=.04). Baseline angiographic lesion criteria were not significantly associated with sustained VA loss. Conclusions Twenty-three percent of eyes with nAMD developed sustained VA loss of ≥15 letters over 5 years of anti-VEGF therapy. Baseline predictors of poor outcomes provide more accurate assessment of the potential benefit from anti-VEGF therapy.
Retinal Nerve Fiber Layer Thickness in a Multi-ethnic Normal Asian Population: the Singapore Epidemiology of Eye Diseases (SEED) Study Ophthalmology (IF 7.479) Pub Date : 2018-12-04 Henrietta Ho, Yih-Chung Tham, Miao Li Chee, Yuan Shi, Nicholas Y.Q. Tan, Kah-Hie Wong, Shivani Majithia, Carol Y. Cheung, Tin Aung, Tien Yin Wong, Ching-Yu Cheng
Purpose To describe variations in retinal nerve fiber layer (RNFL) thickness based on spectral-domain OCT (SD-OCT) in a multi-ethnic Asian population. Design Population-based, cross-sectional study. Participants: Ethnic Chinese, Malay and Indian adults, aged greater than 48 years without glaucoma, recruited from the Singapore Epidemiology of Eye Diseases (SEED) Study. Methods All participants underwent standardized systemic and ocular examinations. RNFL thickness was measured using SD-OCT. Participants with poor quality scans were excluded. Linear regression models were used to investigate the associations of ocular and systemic factors with average RNFL thickness. Generalised estimating equation models were used to account for correlation between both eyes. Main Outcome Measure Average RNFL thickness Results 4,475 participants (8,178 eyes) consisting of 1,371 Chinese, 1,303 Malay, and 1,801 Indian adults contributed to this analysis. Average RNFL thickness measured was 95.7 ± 9.6 μm in Chinese, 94.9 ± 10.6 μm in Malays and 87.3 ± 10.6 μm in Indians (p < 0.001). Multivariable analysis adjusted for age, gender and ethnicity revealed a reduction in RNFL thickness with increased IOP and axial length (p < 0.001 for both), as well as a diagnosis of diabetes (p = 0.04); greater RNFL thickness was associated with increased disc area (p < 0.001), signal strength (p < 0.001) and low-density lipoprotein cholesterol (p = 0.02). When these significant variables were taken into account, the average RNFL thickness of Indian participants was significantly thinner compared with Chinese participants (7.45 μm thinner on average [95% Confidence Interval, 6.75 – 8.15 μm; p < 0.001), whereas there was no significant difference in average RNFL thickness between Malay and Chinese participants (p = 0.15). Conclusions Average and regional RNFL thicknesses were significantly thinner in Indian compared to Chinese and Malay eyes. Results of the study highlights the need to acquire more refined normative data for the comparison of individual patients to others of similar ethnic background while accounting for ocular factors that could influence RNFL thickness. This may in turn improve the sensitivity and specificity of glaucoma detection.
Projection of Long-Term Visual Acuity Outcomes Based on Initial Treatment Response in Neovascular Age-Related Macular Degeneration Ophthalmology (IF 7.479) Pub Date : 2018-08-24 Vuong Nguyen, Vincent Daien, Robyn Guymer, Stephanie Young, Alex Hunyor, Samantha Fraser-Bell, Adrian Hunt, Mark C. Gillies, Daniel Barthelmes,
Purpose To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3-year visual acuity (VA) outcomes. Design Database study, prospectively designed. Participants Treatment-naïve eyes in the Fight Retinal Blindness! registry that commenced anti-VEGF therapy between January 1, 2007, and March 1, 2014, that received 3 anti-VEGF injections within the first 3 months. Methods The early response was defined as occurring up until the fourth injection. Various early response metrics were explored: (1) achieving good VA (≥70 letters; Snellen equivalent, 20/40), (2) absolute change in VA from baseline, (3) time to first grading of the choroidal neovascular lesion as inactive, and (4) maximum rate of VA change between successive injections. Main Outcome Measures Proportion of eyes achieving ≥70 letters 3 years. Results This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was associated significantly with (1) having good vision by the fourth injection (VA ≥70 vs. VA <70 letters: odds ratio [OR], 9.8; 95% confidence interval [CI], 6.5–14.7), (2) small (1–5 letters) or large (>5 letters) early VA gains (vs. early VA loss: OR, 1.8; 95% CI, 1.2–2.6; P = 0.002; and OR, 1.8; 95% CI, 1.3–2.5; P < 0.001), (3) fewer injections until first grading of lesion inactivity (≤3 vs. >3 injections: OR, 1.6; 95% CI, 1.2–2.1; P < 0.001), (4) gradual change (between –4 and 4 letters) or rapid gains (≥5 letters) between successive injections (vs. rapid loss: OR, 1.7; 95% CI, 1.1–2.6; P = 0.015; and OR, 1.6; 95% CI, 1.1–2.3; P = 0.018). Eyes that achieved small or large early gains had similar vision at 3 years (65.0 and 64.7 letters, respectively) and had better vision than eyes with early VA loss (57.2 letters). Conclusions Attainment of good vision by the fourth injection was associated strongly with 3-year visual outcomes, whereas other early response parameters showed a moderate association. The early response during the initial 3 monthly injections can be a useful guide for subsequent treatment decisions.
Evaluating Refractive Outcomes after Cataract Surgery Ophthalmology (IF 7.479) Pub Date : 2018-08-25 Petros Aristodemou, John M. Sparrow, Stephen Kaye
Purpose To compare methods for evaluating refractive outcomes after cataract surgery to detect outliers. Design Case series database study of the evaluation of diagnostic technology. Participants Consecutive patients who had uneventful cataract operations over a 5-year period. Methods The intended and postoperative refractive outcome and differences between these were analyzed as a spherical equivalent, cylinder, and spherocylinder. The average keratometry and differences between steep and flat keratometric meridians were used to calculate the intended refractive error. Main Outcome Measures Outliers were defined as patients for whom the difference between the intended and postoperative refractive errors was more than 3 standard deviations (SDs) away from the mean. Results A total of 9000 patients were included. Twelve patients had missing data and were excluded. The mean intended refractive outcome was −0.12+0.12×2 (95% lower confidence limit [LCL], −1.94+1.06×44; 95% upper confidence limit [UCL], +0.77+1.05×140). The actual postoperative refractive error was −0.30+0.47×6 (95% LCL, −2.36+1.31×36; 95% UCL, +1.00+1.18×148) with a difference from the intended of −0.18+0.35×7 (95% LCL, −1.91+1.22×38; 95% UCL, +0.75+1.09×145). Treating the components of the refractive error independently, outliers were observed in 82 eyes (0.91%) based on the sphere, 46 eyes (0.51%) based on the spherical equivalent, 115 eyes (1.28%) based on treating the cylinder as a scalar, and 76 eyes (0.85%) based on treating the cylinder as a vector. When the differences between the intended and postoperative refractive errors were calculated as a compound spherocylinder, outliers were observed for 233 eyes (2.59%). Conclusions Treating the intended refractive outcome as a spherocylinder improves the precision for detecting clinically significant refractive outliers.
Determining Subclinical Edema in Fuchs Endothelial Corneal Dystrophy. Revised Classification using Scheimpflug Tomography for Preoperative Assessment Ophthalmology (IF 7.479) Pub Date : 2018-08-25 Susan Y. Sun, Katrin Wacker, Keith H. Baratz, Sanjay V. Patel
Purpose To determine if Scheimpflug tomography can identify subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD), and to recommend a new classification of FECD for clinical practice and research. Design Cross-sectional study with follow-up of outcomes. Participants Ninety-three eyes from 57 subjects with a range of severity of FECD and 74 eyes from 40 subjects with normal corneas. Methods Corneas were clinically assessed for FECD and corneal edema by using slit-lamp biomicroscopy, and categorized as having clinically definite edema (obvious visible edema), being suspicious for subclinical edema (possible corneal thickening without obvious edema on slit-lamp examination), or not having edema (no clinical suspicion of edema). Tomographic pachymetry and elevation maps derived from Scheimpflug images were evaluated by 3 masked observers for specific features believed to be consistent with corneal edema. FECD clinical disease course and outcomes were reviewed from the time of Scheimpflug image acquisition to the last available follow-up. Main Outcome Measures Presence of tomographic features: (1) loss of parallel isopachs, (2) displacement of the thinnest point of the cornea, and (3) focal posterior corneal surface depression. Clinical outcomes included the change in central corneal thickness (CCT) and vision after endothelial keratoplasty (EK). Results The 3 specific tomographic features were all present in all FECD corneas with clinically definite edema (n = 15), in ≥81% of FECD corneas suspicious for subclinical edema (n = 16), in ≤42% of FECD corneas deemed not to have edema (n = 62), and in ≤5% of normal corneas (n = 74). Corneas suspicious for subclinical edema that subsequently underwent EK (n = 9) all had at least 2 of the tomographic features present before EK, and improvement in vision, CCT, and tomographic features after EK confirmed the presence of subclinical edema preoperatively. Conclusions Subclinical corneal edema in FECD can be detected by Scheimpflug tomography. We recommend classifying FECD corneas as having clinically definite edema (based on slit-lamp examination), subclinical edema (based on tomographic features without clinically definite edema), or no edema (no tomographic or slit-lamp features of edema). This classification is independent of CCT and should be considered when evaluating FECD eyes for cataract surgery or EK.
Childhood Lensectomy Is Associated with Static and Dynamic Reduction in Schlemm Canal Size Ophthalmology (IF 7.479) Pub Date : 2018-08-30 Moritz C. Daniel, Adam M. Dubis, Maria Theodorou, Ana Quartilho, Gillian Adams, John Brookes, Maria Papadopoulos, Peng T. Khaw, Annegret H. Dahlmann-Noor
Purpose To compare Schlemm canal (SC) and trabecular meshwork (TM) in children with healthy eyes and those with and without glaucoma after lensectomy. Design Cross-sectional observational study. Participants Fifty children 4 to 16 years of age with healthy eyes and 48 children who underwent lensectomy (124 healthy and 72 postlensectomy eyes). Methods Anterior segment (AS) OCT (Tomey SS-1000 CASIA; Tomey, Nagoya, Japan) of the nasal iridocorneal angle at 2 levels of accommodative effort (2.5 diopters [D] and 15 D). For each parameter and state of accommodation, a random effects model was fitted to estimate differences between healthy eyes and eyes with history of lensectomy. Main Outcome Measures Dimensions of SC and TM and conventional AS OCT iridocorneal angle measurements. Results The horizontal diameter of SC and its cross-sectional area (CSA) are significantly smaller in eyes that have undergone lensectomy versus healthy eyes. Accommodative effort increases SC size in healthy eyes, but not in eyes that have undergone lensectomy. Conclusions Lensectomy is associated with a reduction in SC size and a loss of physiologic SC dilatation during accommodative effort, which may reflect a reduction in outflow facility and may contribute to the development of glaucoma after lensectomy.
Tolerating Subretinal Fluid in Neovascular Age-Related Macular Degeneration Treated With Ranibizumab Using a Treat and Extend Regimen: FLUID Study 24 Month Results Ophthalmology (IF 7.479) Pub Date : 2018-11-29 Robyn H. Guymer, Caroline M. Markey, Ian L. McAllister, Mark C. Gillies, Alex P. Hunyor, Jennifer J. Arnold,
Purpose To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF. Design Multi-center, randomized, 24-month, phase IV, single-masked, non-inferiority clinical trial. Subjects Subjects presenting with treatment-naive nAMD. Intervention Subjects with active subfoveal choroidal neovascularization (CNV) were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF) (intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal centre) before extending treatment intervals. A 5-letter non-inferiority margin was applied to the primary outcome measure. Main outcome measures Mean change in best-corrected visual acuity (BCVA), mean change in central subfield thickness (CST) and number of ranibizumab injections from baseline to month 24. Results Of the 349 subjects randomized (intensive: 174; relaxed: 175), 279 (79.9%) completed the month 24 visit. Baseline characteristics were well balanced except area of lesion and area of CNV. The mean (SD) change in BCVA from baseline to month 24 was 3.0 (16.3) letters in the intensive group and 2.6 (16.3) letters in the relaxed group, demonstrating non-inferiority of the relaxed to the intensive treatment (P=0.99). Similar proportions of the intensive and relaxed groups achieved ≥20/40 VA (53.5% and 56.6%, respectively; P=0.92) and ≤20/200 VA (8.7% and 8.1%, respectively; P=0.52). Resultswere supported by the per protocol analysis and adjustment for confounding baseline factors. Subjects in the relaxed group received fewer ranibizumab injections over 24 months (mean [SD]; 15.8 [5.9]) than those in the intensive group (17 [6.5]; p=0.001). Significantly more subjects in the intensive group never extended beyond 4-weekly treatment intervals (13.5%) than in the relaxed group (2.8%; p=0.003) and significantly more subjects in the relaxed group extended to and maintained 12-weekly treatment intervals (29.6%) than the intensive group (15.0%; p=0.005). Conclusions Patients treated with a ranibizumab T&E protocol that tolerated some SRF achieved VA that is comparable, with fewer injections, to that achieved when treatment aimed to completely resolve all SRF.
DeepSeeNet: A deep learning model for automated classification of patient-based age-related macular degeneration severity from color fundus photographs Ophthalmology (IF 7.479) Pub Date : 2018-11-22 Yifan Peng, Shazia Dharssi, Qingyu Chen, Tiarnan D. Keenan, Elvira Agrón, Wai T. Wong, Emily Y. Chew, Zhiyong Lu
Purpose In assessing the severity of age-related macular degeneration (AMD), the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale predicts the risk of progression to late AMD. However, its manual use requires the time-consuming participation of expert practitioners. While several automated deep learning (DL) systems have been developed for classifying color fundus photographs of individual eyes by AREDS severity score, none to date has utilized a patient-based scoring system that employs images from both eyes to assign a severity score. Design DeepSeeNet, a DL model, was developed to classify patients automatically by the AREDS Simplified Severity Scale (score 0-5) using bilateral color fundus images. Participants: DeepSeeNet was trained on 58,402 and tested on 900 images from the longitudinal follow up of 4,549 participants from AREDS. Gold standard labels were obtained using reading center grades. Methods DeepSeeNet (composed of three sub-networks) simulates the human grading process by first detecting individual AMD risk factors (drusen size; pigmentary abnormalities) for each eye and then calculating a patient-based AMD severity score using the AREDS Simplified Severity Scale. Main Outcome Measures Overall accuracy, specificity, sensitivity, Cohen’s kappa, area under the curve (AUC). The performance of DeepSeeNet was compared to that of retinal specialists. Results: DeepSeeNet performed better on patient-based, multi-class classification (accuracy=0.671; kappa=0.558) than retinal specialists (accuracy=0.599; kappa=0.467) with high AUCs in the detection of large drusen (0.94), pigmentary abnormalities (0.93) and late AMD (0.97), respectively. DeepSeeNet also outperformed retinal specialists in the detection of large drusen (accuracy 0.742 vs 0.696; kappa 0.601 vs 0.517) and pigmentary abnormalities (accuracy 0.890 vs 0.813; kappa 0.723 vs 0.535) but showed lower performance in the detection of late AMD (accuracy 0.967 vs 0.973; kappa 0.663 vs 0.754). Conclusions By simulating the human grading process, DeepSeeNet demonstrated high accuracy with increased transparency in the automated assignment of individual patients to AMD risk categories based on the AREDS Simplified Severity Scale. These results highlight the potential of deep learning systems to assist and enhance clinical decision-making processes in AMD patients such as early AMD detection and risk prediction for developing late AMD. DeepSeeNet is publicly available on https://github.com/ncbi-nlp/DeepSeeNet.
The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma A Report by the American Academy of Ophthalmology Ophthalmology (IF 7.479) Pub Date : 2018-11-22 Ambika Hoguet, Philip P. Chen, Anna K. Junk, Prithvi Mruthyunjaya, Kouros Nouri-Mahdavi, Sunita Radhakrishnan, Hana L. Takusagawa, Teresa C. Chen
Purpose To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. Methods Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded owing to poor study design and lack of relevance to the topic under evaluation. Results The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP rise and the type of intravitreal injection, number of intravitreal injections, pre-existing glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. Conclusions Intravitreal injection of anti-VEGF agents results in an immediate and transient rise in IOP. A long-term increase in IOP may be seen as well, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Even though pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.
The Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) Ophthalmology (IF 7.479) Pub Date : 2018-11-22 Roxane J. Hillier, Tina Felfeli, Alan R. Berger, David T. Wong, Filiberto Altomare, David Dai, Louis R. Giavedoni, Peter J. Kertes, Radha P. Kohly, Rajeev H. Muni
Purpose The optimal surgical intervention to repair certain common configurations of uncomplicated rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. Design Prospective randomized controlled trial. Participants Patients with RRD presenting with a single retinal break, or group of breaks within one clock hour, above the 8 and 4 o’clock meridians. Methods Patients were randomized to either the PnR or PPV intervention group. Macula-on and -off cases were assigned to intervention group by stratified randomization and treated within 24 and 72 hours respectively. Main Outcome Measures The primary outcome was 1-year ETDRS visual acuity. Important secondary outcomes were subjective visual function (NEI VFQ-25), metamorphopsia score (M-CHARTS™) and primary anatomical success. Results 176 patients were recruited between August 2012 and May 2016. ETDRS visual acuity following PnR exceeded PPV by 4.9 letters at 12 months (79.9±10.4 versus 75.0±15.2, P=0.024). Mean ETDRS visual acuity was also superior for the PnR group compared to PPV at 3 months (78.4±12.3 versus 68.5±17.8) and 6 months (79.2±11.1 versus 68.6±17.2). Composite NEI VFQ-25 scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared to PPV at 12 months (0.14±0.29 versus 0.28±0.42, P=0.026). Primary anatomical success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P=0.045), with 98.7% and 98.6%, respectively achieving secondary anatomical success. 65% of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months, versus 16% for PnR (P<0.001). Conclusions PnR should be considered the first line treatment for RRD in patients fulfilling PIVOT recruitment criteria. PnR offers superior visual acuity, less vertical metamorphopsia and reduced morbidity when compared to PPV.
Orthokeratology for the Prevention of Myopic Progression in Children A report by the American Academy of Ophthalmology Ophthalmology (IF 7.479) Pub Date : 2018-11-23 Deborah K. VanderVeen, Raymond T. Kraker, Stacy L. Pineles, Amy K. Hutchinson, Lorri B. Wilson, Jennifer A. Galvin, Scott R. Lambert
Objective To review the published evidence to evaluate the ability of orthokeratology (Ortho-K) treatment to reduce myopic progression in children and adolescents compared with the use of spectacles or daytime contact lenses for standard refractive correction. Methods Literature searches of the PubMed database, the Cochrane Library, and the databases of clinical trials were last conducted on May 23, 2017 with no date restrictions but limited to articles published in English. These searches yielded 162 citations, of which 13 were deemed clinically relevant for full-text review and inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to the selected studies. Results The 13 articles selected for inclusion include 3 prospective, randomized clinical trials; 7 nonrandomized, prospective comparative studies; and 3 retrospective case series. One study provided level I evidence, 11 studies provided level II evidence, and 1 study provided level III evidence. Most studies were performed in populations of Asian ethnicity. Change in axial length was the primary outcome for 10 of 13 studies, and change in refraction was the primary outcome for 3 of 13 studies. In these studies, Ortho-K typically reduced axial elongation by approximately 50% over a 2-year study period. This corresponds to average axial length change values of about 0.3 mm for Ortho-K patients compared with 0.6 mm for control patients, which corresponds to a typical difference in refraction of about 0.5 D. Younger-age groups and individuals with larger than average pupil size may have a greater effect with Ortho-K. Rebound can occur after discontinuation or change to alternative refractive treatment. Conclusions Orthokeratology may be effective in slowing myopic progression for children and adolescents, with a potentially greater effect when initiated at an early age (6–8 years). Safety remains a concern because of the risk of potentially blinding microbial keratitis from contact lens wear.
Follow up at 5 Years of Non-Fibrotic Scars in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Ophthalmology (IF 7.479) Pub Date : 2018-11-23 Ebenezer Daniel, Gui-shuang Ying, Benjamin J. Kim, Cynthia A. Toth, Frederick Ferris, Daniel F. Martin, Juan E. Grunwald, Glenn J. Jaffe, Joshua L. Dunaief, Wei Pan, Maureen G. Maguire,
Objective To describe changes in visual acuity (VA) and macular morphology at 5 years in eyes with non-fibrotic scars (NFS) identified at 1 year in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Prospective cohort study within a randomized clinical trial. Participants Participants in CATT. Methods Participants assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens were released from the clinical trial protocol after 2 years and recalled at 5 years. NFS was identified on color images at year 1 as flat, small, well-circumscribed areas of pigmentation with varying degrees of central hypopigmentation without exposure of underlying choroidal vessels, at the site of baseline choroidal neovascularization (CNV). Follow-up images were assessed for changes in and around the NFS. Main outcome measures Changes in pigmentation, VA, development of fibrotic scar (FS), non-geographic (NGA) and geographic atrophy (GA), retinal fluid on optical coherent tomography, and fluorescein leakage. Results Among 474 eyes with images at 1, 2 and 5 years, 39 (8.2%) had NFS at 1 year with a mean VA of 80 letters (≈ 20/25). Among these eyes, FS developed in 5% at 2 and 28% at 5 years. NGA was observed in 34%, 47% and 65% of eyes at 1, 2 and 5 years, respectively. GA developed in 5% of eyes at 2 and 21% at 5 years. Among eyes with NFS, FS or no scar at 1 year, mean VA at 5 years was 73 letters (≈ 20/32), 48 (≈ 20/100) and 62 (≈ 20/63), respectively. At 5 years, NFS eyes had less GA, less intraretinal fluid, more subretinal fluid, and less sub-RPE fluid (all p<0.01). Among NFS eyes, mean thickness of the retina, subretinal tissue complex and total retina did not change across years 1 to 5 (p>0.50). The proportion of eyes with fluid on OCT also did not change (p=0.36). Subretinal hyperreflective material disappeared by 5 years in 40% of eyes with NFS. Conclusion These results indicate that, on average, eyes with NFS after anti-VEGF treatment have good visual acuity not only at 1 and 2 years, but also through 5 years
Rhegmatogenous Retinal Detachment In Children: Clinical Factors Predictive Of Successful Surgical Repair Ophthalmology (IF 7.479) Pub Date : 2018-11-10 Jesse M. Smith, Laura T. Ward, Justin H. Townsend, Jiong Yan, Andrew M. Hendrick, Blaine E. Cribbs, Steven Yeh, Nieraj Jain, G. Baker Hubbard
Objective To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). Design Retrospective interventional case series. Subjects 212 eyes of 191 patients, aged 0-18 years, undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow up of 3 months. Methods Patients were divided into three age groups (0-6 years, 7-12 years, 13-18 years) and comparisons were made using bivariate and multivariable generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. Main Outcome Measures Complete reattachment of the retina at final follow up. Results Of a total of 212 eyes, 166 (78%) achieved total reattachment at final follow up. Mean follow up was 36.3 months. RRD associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR] 0.45, 95 % confidence interval [CI] 0.22 - 0.91), while RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR 2.3, 95% CI 1.2 - 4.4). Subtotal RRD was more likely to be successfully repaired than total RRD (OR 3.6, 95% CI 1.5 - 8.4, p = 0.0100), and eyes with previous vitreoretinal surgery were less likely to have successful repair (OR 0.30, 95% CI 0.12 – 0.78, p = 0.0258). There was no significant difference between age groups in the rate of surgical success (p = 0.55). There was a significantly higher success rate with primary scleral buckle (SB) (63%, OR 2.2, 95% CI 1.1- 4.5) and combined scleral buckle/vitrectomy (SB/PPV) (68%, OR 2.3 95% CI 1.1-5.1) compared to vitrectomy (PPV) alone (51%). Conclusions Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to present with RRD involving the macula but there was no difference between age groups in successful reattachment at final follow up. Primary PPV had a lower rate of success than SB or combined SB/PPV.
Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-label Extension of RIDE and RISE Studies Ophthalmology (IF 7.479) Pub Date : 2018-11-09 Jennifer K. Sun, Pin-wen Wang, Sarah Taylor, Zdenka Haskova
Objective To evaluate durability of diabetic retinopathy (DR) improvements after a change in ranibizumab dosing from monthly to individualized pro re nata (PRN) therapy. Design Pooled analysis of the open-label extension (OLE) of RIDE/RISE (NCT00473382/NCT00473330) patients with DR and diabetic macular edema (DME). Participants Patients who completed 36-month participation in RIDE/RISE and entered the OLE. Methods In the RIDE/RISE studies, patients (N = 759) were randomized 1:1:1 to ranibizumab 0.3 mg monthly, 0.5 mg monthly, or monthly sham injections with rescue macular laser available after 6 months, per protocol-specified criteria. After 24 months, sham patients crossed over to ranibizumab 0.5 mg monthly. After 36 months in the core studies, patients in the OLE (n = 500) could receive ranibizumab 0.5 mg through an individualized PRN dosing regimen based on predefined DME re-treatment criteria. DR severity was evaluated photographically using the Early Treatment Diabetic Retinopathy Study DR severity scale. Main Outcome Measure Change in DR severity from months 36 to 48 by re-treatment status. Results Among patients who entered the OLE, 121/500 (24%) did not require additional ranibizumab injections. In total, 442 patients had evaluable DR outcomes during the OLE; 367 had evaluable DR at months 36 and 48. Among patients not requiring ranibizumab re-treatment from months 36 to 48 (88/367), 57% to 78%, 0% to 7%, and 22% to 36% experienced DR severity stability, ≥2-step improvement, and ≥2-step worsening, respectively. Among patients requiring ranibizumab re-treatment (279/367), 84% to 94%, 2%, and 3% to 14% experienced DR severity stability, ≥2-step improvement, and ≥2-step worsening, respectively. On average, vision improvements were maintained during the OLE regardless of change in DR severity. Conclusions DR severity improvements with ranibizumab were maintained in the majority of patients in the OLE after switching from ranibizumab monthly to an individualized best-corrected visual acuity– and optical coherence tomography–based ranibizumab 0.5 mg PRN dosing regimen. Because nearly one-third of OLE patients not requiring further therapy for DME experienced DR worsening, once DME resolves, patients should be watched carefully for worsening of DR and possible need for more frequent follow-up and/or treatment of vision-threatening disease with anti-VEGF or other modalities.
24-Hour Intraocular Pressure Control with Fixed-dose Combination Brinzolamide 1%/Brimonidine 0.2%: A Multicenter, Randomized Trial Ophthalmology (IF 7.479) Pub Date : 2018-11-04 Robert N. Weinreb, Jason Bacharach, Robert D. Fechtner, Malik Y. Kahook, David Wirta, Steve Burmaster, Xiangyi Meng, Douglas A. Hubatsch
Purpose To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. Design Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and non-academic sites in the USA. Participants Subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT) aged ≥18 years, with mean baseline IOP measurements in at least one eye of ≥21 and <28 mmHg. Methods Duplicate, mean pneumatonometer IOP measurements were collected every 2 hours over a 24-hour period in controlled light conditions in overnight facilities. Daytime (8 AM–8 PM) and nocturnal (10 PM–6 AM) IOP measurements were collected in a sitting or supine position, respectively. Baseline 24-hour IOP was measured in untreated subjects after a washout phase (up to 4 weeks) and eligibility phase. Following the baseline visit, subjects were randomized 1:1 to receive masked BBFC or Vehicle, one drop three times daily (8 AM, 3 PM, 10 PM) for 4 weeks. At Week 4, IOP measurements were repeated in both groups under the same conditions. Main Outcome Measure Mean change from Baseline in 24-hour IOP at Week 4. Results Of 125 subjects randomized, 123 (98%; BBFC, n=62; Vehicle, n=61) completed the study. No subjects randomized to BBFC discontinued from the study. At Week 4, BBFC-treated eyes had significantly reduced mean 24-hour IOP vs Vehicle (least squares mean difference [95% confidence interval]: -2.5 [-3.3, -1.7]; P < 0.001); daytime (-3.4 [ 4.3, -2.6]; P < 0.001) and nocturnal (-1.2 [-2.3, 0.0]; P = 0.053) reductions were observed. Mean change from Baseline was significantly different between BBFC- and Vehicle-treated eyes at all day-time points and three of five nocturnal time points (10 PM, 12 AM, 6 AM; secondary endpoint). The frequency of adverse events was similar between treatment groups; in the BBFC arm, ocular hyperemia, corneal abrasion, and dysgeusia were the most frequently reported, consistent with events described in the drug label. Conclusions This first large, multicenter study of 24-hour IOP control with BBFC met its primary endpoint; BBFC demonstrated significantly superior 24-hour IOP-lowering efficacy vs Vehicle following 4 weeks of three-times-daily treatment in subjects with OAG or OHT.
The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration Ophthalmology (IF 7.479) Pub Date : 2018-10-31 Robert F. Mullins, Gerald McGwin, Karen Searcey, Mark E. Clark, Elizabeth L. Kennedy, Christine A. Curcio, Edwin M. Stone, Cynthia Owsley
Objective To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD), and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD. Design Cross-sectional Subjects Older adults aged ≥60 years in normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9). Methods Single nucleotide polymorphisms were genotyped in the CFH and ARMS2 genes using a Taqman assay. RMDA was assessed in one eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking. Main Outcome Measure RIT. Results The sample consisted of 543 participants having both genotype and RIT determination; 408 were in normal macular health and 135 had AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted p=0.0001 and p=0.0023 respectively). For normal subjects the A69S variant in ARMS2 was associated with higher RIT (adjusted p=0.0011), whereas CFH Y402H was not (adjusted p=0.2175). For AMD cases, the A69S variant of ARMS2 and CFH Y402H were associated with higher RIT (adjusted p=0.0182 and p=0.0222 respectively). Those with a greater number of high-risk ARMS2 and CFH alleles had higher RIT, in both normal and AMD groups (adjusted p=0.0002 and p<0.0001 respectively). Conclusions We report a novel association wherein older adults with high risk ARMS2 and CFH genotypes are more likely to have delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those in normal macular health with the ARMS2 A69S allele have delayed RMDA. Understanding ARMS2 function is a research priority.
Pre-operative vision and surgeon volume as predictors of visual outcomes following cataract surgery Ophthalmology (IF 7.479) Pub Date : 2018-10-25 Bobeck S. Modjtahedi, Michaela M. Hull, John Adams, Stephen Munz, Tiffany Q. Luong, Donald S. Fong
Purpose To evaluate the relationship between pre-operative vision and surgeon volume with visual outcomes following cataract surgery. Design Retrospective cohort study. Subjects Patients > 18 years old enrolled in Kaiser Permanente Southern California health plan that underwent cataract surgery by non-trainee surgeons. Methods Patients who underwent cataract surgery between December 31, 2013 and January 1, 2015 were included. A multivariate analysis using GAMM (Generalized Additive Mixed Models) was performed to determine the relationship between surgeon volume and post-operative visual acuity after controlling for patient age, pre-operative visual acuity, history of diabetes, and history of diabetic retinopathy. Modeling was done for the relationship between pre-operative vision and visual outcomes while controlling for surgeon volume, patient age, history of diabetes, and history of diabetic retinopathy. Main outcome measure Absolute letter change and percentage of patients to achieve of > 5 letter Early Treatment Diabetic Retinopathy Study (ETDRS) gain post-operatively. Results There were 103,920 cataract surgeries performed by 136 surgeons included in this analysis. Patients whose surgeons performed < 91.0 surgeries/year [95% Confidence Interval (CI) 61.1-139, p<0.05] gained fewer letters post-operatively while those whose surgeons performed >91 but < 227 surgeries/year (95% CI 169- ∞, p<0.05) gained more letters than average. Although statistically significant, the difference between the lowest and highest performing groups was approximately 1.25 letters. Surgeons who performed <110 surgeries/year (95% CI 81.7-149, p<0.05) had less patients who gained > 5 letters. Surgeons who performed >110 but <293 surgeries/year (95% CI 232- ∞, p<0.05) were as high as 15-20% more likely to have patients who gained > 5 letters. Patients with pre-operative vision < 74.7 letters (95% CI 74.7-74.8, p<0.05) and < 75.8 letters (95% CI 75.8-75.9, p<0.05) gained more letters and were more likely to gain > 5 letters post-operatively, respectively Conclusion Patients whose vision is approximately 20/32 or worse are more likely to have significant visual gains after cataract surgery. Although statistically significant differences exist in post-operative vision based on surgeon volume, these do not appear to be clinically meaningful. Overall, visual outcomes are clinically and functionally comparable across a wide range of surgeon volumes.
Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Noninfectious Uveitis Affecting the Posterior Segment: 12-Month Results Ophthalmology (IF 7.479) Pub Date : 2018-10-25 Glenn J. Jaffe, Stephen Foster, Carlos Pavesio, Dario Paggiarino, Gerard E. Riedel
Objective To assess the safety and efficacy of an intravitreal ﬂuocinolone acetonide insert (FAi) to manage inflammation associated with noninfectious posterior uveitis. Design Multi-center, randomized, prospective, doubled-masked, sham-controlled, 3-year, phase 3 clinical trial. Participants A total of 129 participants with recurrent noninfectious posterior uveitis were randomly assigned to FAi (N=87) or sham injection (N=42). The more severely affected eye in participants with bilateral disease was designated as the study eye. Methods The insert (FA 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, optical coherence tomography, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28, and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. Results The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P<0.001) with FAi versus sham, respectively. Fewer recurrences per study eye (mean of 0.7 versus 2.5), lower incidence of ≥15 letter decrease in best corrected visual acuity (14% vs 31%), and reduced systemic (19% vs 40%) and local (7% vs 62%) uveitis adjunctive treatments were observed with FAi versus sham, respectively. FAi had higher rates of cataract. Intraocular pressure-lowering treatment use was similar. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. Conclusion Noninfectious posterior uveitis was successfully managed in this study population; FAi eyes had fewer uveitis recurrence episodes, required fewer adjunctive treatments, and had less visual acuity loss compared with sham eyes. FAi treatment had higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an office setting. [300/300 words]
A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years of Age Ophthalmology (IF 7.479) Pub Date : 2018-10-22 Jonathan M. Holmes, Ruth E. Manny, Elizabeth L. Lazar, Eileen E. Birch, Krista R. Kelly, Allison I. Summers, Stacy R. Martinson, Aparna Raghuram, Jeffrey D. Colburn, Christine Law, Justin D. Marsh, Derek P. Bitner, Raymond T. Kraker, David K. Wallace,
Purpose To compare visual acuity (VA) improvement in children aged 7 to 12 years with amblyopia treated with a binocular iPad® game plus continued spectacle correction versus continued spectacle correction alone. Design Multi-center randomized clinical trial Participants One hundred thirty-eight participants aged 7 to 12 years with amblyopia (33 to 72 letters, i.e., approximately 20/200 to 20/40) resulting from strabismus, anisometropia, or both. Participants were required to have at least 16 weeks of optical treatment in spectacles if needed or demonstrate no improvement in amblyopic-eye visual acuity (VA) for at least 8 weeks prior to enrollment. Methods Eligible participants (mean age 9.6 years, mean baseline VA of 59.6 letters, history of prior amblyopia treatment other than spectacles in 96%) were randomly assigned to treatment for 8 weeks with the dichoptic binocular Dig Rush iPad game (prescribed for 1 hour per day 5 days per week) plus spectacle wear if needed (N=69) or continued spectacle correction alone if needed (N=69). Main Outcome Measures Change in amblyopic-eye VA from baseline to 4 weeks, assessed by a masked examiner. Results At 4 weeks, mean amblyopic-eye VA letter score improved from baseline by 1.3 (2-sided 95% confidence interval (CI): 0.1 to 2.6; 0.026 logMAR) with binocular treatment and by 1.7 (2-sided 95% CI: 0.4 to 3.0; 0.034 logMAR) with continued spectacle correction alone. After adjusting for baseline VA, the letter score difference between groups (binocular minus control) was -0.3 (95% CI: -2.2 to 1.5, p=0.71, difference of -0.006 logMAR). No difference in letter scores was observed between groups when the analysis was repeated after 8 weeks of treatment (adjusted mean: -0.1, 98.3% CI: -2.4 to 2.1). For the binocular group, adherence data from the iPad indicated that slightly more than half of the participants (58% and 56%) completed >75% of prescribed treatment by the 4- and 8-week visits, respectively. Conclusions In children aged 7 to <13 years, who have received previous treatment for amblyopia other than spectacles, there was no benefit to visual acuity or stereoacuity from 4 or 8 weeks of treatment with the dichoptic binocular Dig Rush iPad game.
Genetic Architecture of Primary Open Angle Glaucoma in Individuals of African Descent: The African Descent & Glaucoma Evaluation Study (ADAGES) III Ophthalmology (IF 7.479) Pub Date : 2018-10-21 Kent D. Taylor, Xiuqing Guo, Linda M. Zangwill, Jeffrey M. Liebmann, Christopher A. Girkin, Robert M. Feldman, Harvey Dubiner, Yang Hai, Brian C. Samuels, Joseph F. Panarelli, John P. Mitchell, Lama A. Al-Aswad, Sung Chul Park, Celso Tello, Jeremy Cotliar, Rajendra Bansal, Paul A. Sidoti, George A. Cioffi, Robert N. Weinreb
Objective Find genetic contributions to glaucoma in African Americans. Design Cross-sectional, case-control study. Participants 1875 POAG cases and 1709 controls, self-identified as African Descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGESIII) and Wake Forest School of Medicine. Methods MegaChip genotypes were imputed to Thousand Genomes data. Association of SNPs with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by Receiver Operator Characteristics (ROC-AUC). Main Outcome: POAG defined by visual field loss without other non-ocular conditions (N=1875). Advanced POAG was defined by age-based mean deviation of visual field (N=946). Results 18,281,920 SNPs met imputation quality r2>0.7 and minor allele frequency>0.005. Association of a novel locus, ENO4, was observed for advanced POAG (rs185815146 beta 0.36, SE 0.065, p<3x10-8). For POAG, an AD signal was observed at 9p21 ED POAG signal (rs79721419; p<6.5x10-5) independent of the previously observed 9p21 ED signal (rs2383204; p<2.3x10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934, p<3.9x10-5) was observed, not in LD with the previously reported ED SNP. Additional previously identified loci associated with POAG in AD were: 8q22, AFAP1, TMCO1. An AUC of 0.62 was observed with an unweighted genetic risk score composed of 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC=0.74 and AUC=0.94, respectively. Conclusions A novel association with advanced POAG in the ENO4 locus was putatively identified in subjects of African descent. In addition to this finding, this GWAS in AD POAG subjects contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine-mapping of regions due to shorter average linkage disequilibrium (FNDC3B). While not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.
Potential lost productivity resulting from the global burden of myopia: systematic review, meta-analysis and modelling Ophthalmology (IF 7.479) Pub Date : 2018-10-17 Kovin S. Naidoo, Timothy R. Fricke, Kevin D. Frick, Monica Jong, Thomas J. Naduvilath, Serge Resnikoff, Padmaja Sankaridurg
Topic We estimated the potential global economic productivity loss due to vision impairment (VI) and blindness from uncorrected myopia and myopic macular degeneration (MMD) in 2015. Clinical relevance Understanding the economic burden of VI associated with myopia is critical to addressing myopia as an increasingly prevalent public health problem. Methods We used systematic review and meta-analysis to estimate the number of people with myopia and MMD corresponding to critical visual acuity thresholds. Spectacle correction coverage was analyzed against country-level variables from the year of data collection; variation in spectacle correction was best described by a model based on human development index, with adjustments for urbanization and age. Spectacle correction and myopia data were combined to estimate the number of people with each level of VI from uncorrected myopia. We then applied disability weights, labor force participation rates, employment rates and gross domestic product per capita to estimate the potential productivity lost among individuals with each level and type of VI due to myopia in 2015 in US$. An estimate of care-associated productivity loss was also included. Results People with myopia are less likely to have adequate optical correction if they are older and live in a rural area of a less developed country. The global potential productivity loss associated with the burden of VI in 2015 was estimated at US$244 billion (95% confidence interval US$49 billion – US$697 billion) from uncorrected myopia, and US$6 billion (US$2 billion – US$17 billion) from MMD. Our estimates suggest that the Southeast Asia, South Asia, and East Asia Global Burden of Disease regions bear the greatest potential burden as a proportion of their economic activity, while East Asia bears the greatest potential burden in absolute terms. Conclusion Even under conservative assumptions, the potential productivity loss associated with VI and blindness from uncorrected myopia is substantially greater than the cost of correcting myopia.
DICER1 Syndrome: Characterization of the ocular phenotype in a family-based cohort study Ophthalmology (IF 7.479) Pub Date : 2018-10-17 Laryssa A. Huryn, Amy Turriff, Laura A. Harney, Ann Garrity Carr, Patricia Chevez-Barrios, Dan S. Gombos, Radha Ram, Robert B. Hufnagel, D. Ashley Hill, Wadih M. Zein, Kris Ann P. Schultz, Rachel Bishop, Douglas R. Stewart
Purpose To characterize the ocular phenotype of DICER1 syndrome Design Prospective, single-center, case-control study Subjects, Participants, and/or Controls One hundred and three patients with an identified germline, pathogenic DICER1 variant (DICER1-carriers) and 69 family control subjects underwent clinical and ophthalmic examination at the National Institutes of Health between 2011 and 2016. Methods All participants were evaluated with a comprehensive ophthalmic exam including best corrected visual acuity, slit-lamp biomicroscopy and a dilated fundus examination. A subset of patients returned for a more detailed evaluation including spectral-domain optical coherence tomography, color fundus photography, fundus autofluorescence imaging, visual field testing, full field electroretinogram and genetic testing for inherited retinal degenerative diseases. Main Outcome Measures Visual acuity and examination findings Results Most DICER1-carriers (97%) maintained a visual acuity of 20/40 or better in both eyes. Twenty three DICER1-carriers (22%) had ocular abnormalities compared with four (6%) family controls (P=0.005). These abnormalities included retinal pigment abnormalities (N=6, 5.8%), increased cup-to-disc ratio (N=5, 4.9%), optic nerve abnormalities (N=2, 1.9%), epiretinal membrane (N=2, 1.9%) and drusen (N=2, 1.9%). Overall, we observed a significant difference (p= 0.03) in the rate of retinal abnormalities in DICER1-carriers (N=11, 11%) vs. controls (N=1; 1.5%). One patient had an unexpected diagnosis of retinitis pigmentosa with a novel variant of unknown significance in PRPF31, and one had optic nerve elevation in the setting of increased intracranial pressure of unclear etiology. Three patients (3%) had DICER1-related ciliary body medulloepithelioma (CBME), two of which were identified during routine examination, a significantly higher rate than that previously reported. Conclusions Ophthalmologists should be aware of the ophthalmic manifestations of the DICER1 syndrome and individuals and families should be counseled on the potential signs and symptoms. We recommend that children with a germline pathogenic variant in DICER1, especially those under the age of 10 years, undergo annual dilated ophthalmic examination, looking for evidence of CBME, signs of increased intracranial pressure and perhaps changes in the retinal pigment epithelium.
Aravind Pseudoexfoliation Study (APEX) - Surgical and First Year Postoperative Results in Eyes Without Phacodonesis and Non-Miotic Pupils Ophthalmology (IF 7.479) Pub Date : 2018-10-17 Aravind Haripriya, Pradeep Y. Ramulu, Shivkumar Chandrashekharan, Rengaraj Venkatesh, Kalpana Narendran, Madhu Shekhar, Rengappa Ramakrishnan, Ravilla D. Ravindran, Alan L. Robin
Purpose To compare: (1) intraoperative complication rates, (2) one-year visual outcomes, and (3) post-operative complication rates over the first post-operative year in eyes with and without pseudoexfoliation (PEX) undergoing cataract surgery. Design Prospective comparative interventional study Participants Nine-hundred thirty eyes with cataract and uncomplicated PEX (without phacodonesis, clinically shallow anterior chambers, or pupil size < 4mm ) and 476 controls with cataract but without PEX recruited from four centers of the Aravind Eye Care System in Southern India. The PEX and control groups were each separately randomized to receive either a single (SA60AT) or three piece acrylic IOL (MA60AS). The PEX group was also randomized to receive or not receive a capsular tension ring (CTR). Methods All eyes underwent phacoemulsification with IOL implantation and were followed at 1 day, 1 month, 3 months and 1 year after surgery. Main Outcome Measures Association of PEX status on intraoperative complication rates, one-year best corrected visual acuity, and any other complications. Results Mean ages were 63.0 ± 6.9 years and 57.9 ± 7.3 years in the PEX and control groups, respectively (p<0.001). PEX subjects were more likely to be male (p=0.014), have a nuclear opalescence grade>4 (p=0.001) and a pupil <6 mm (p< 0.001) when compared to controls. Intraoperative complication rates were 2.9% and 1.9% in the PEX and control groups, respectively (p=0.29). One year post-operative best-corrected visual acuity was comparable (p=0.09). Complication rates at 1 year were 2.7% and 2.5% in the PEX and control groups (p=0.82). Average endothelial cell loss was 14.7% in PEX group and 12.7% in control group at 1 year (p=0.066) when adjusting for age and nuclear opacity). Conclusions We evaluated PEX eyes without shallow anterior chamber, small pupils or apparent zonulopathy. These may represent eyes with lower risks of complications. Despite smaller pupils and denser cataracts, PEX eyes without clinically apparent preoperative zonulopathy were not at a higher risk of intra or post-operative complications, or worse visual outcomes after cataract surgery.
Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis Ophthalmology (IF 7.479) Pub Date : 2018-10-16 Dyfrig A. Hughes, Giovanna Culeddu, Catrin Plumpton, Eifiona Wood, Andrew D. Dick, Ashley P. Jones, Andrew McKay, Paula R. Williamson, Sandrine Compeyrot Lacassagne, Ben Hardwick, Helen Hickey, Patricia Woo, Michael W. Beresford, Athimalaipet V. Ramanan
Objectives To investigate the cost-effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with Juvenile Idiopathic Arthritis (JIA-U). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents aged 2 to 18 years with persistently active JIA-U, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE trial [ISRCTN10065623] of methotrexate (up to 25mg per week) with or without fortnightly administered adalimumab (20mg or 40mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main outcome measures Medical costs to the National Health Service in the UK, utility of defined health states, quality-adjusted life years (QALY), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39,316 with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129,025 per QALY gained. The probability of cost-effectiveness at a threshold of £30,000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost-effective. Conclusions Adalimumab is clinically effective in JIA-U, however its cost-effectiveness is not demonstrated compared with methotrexate alone in the UK setting.
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- J. Acad. Nutr. Diet.
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- J. Alloys Compd.
- J. Am. Ceram. Soc.
- J. Am. Chem. Soc.
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- J. Phys. Chem. C
- J. Phys. Chem. Lett.
- J. Polym. Sci. A Polym. Chem.
- J. Porphyr. Phthalocyanines
- J. Power Sources
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- J. Taiwan Inst. Chem. E.
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- New J. Chem.
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- Prog. Solid State Chem.