Guidelines on Diabetic Eye Care : The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings Ophthalmology (IF 8.204) Pub Date : 2018-05-24 Tien Y. Wong, Jennifer Sun, Ryo Kawasaki, Paisan Ruamviboonsuk, Neeru Gupta, Van Charles Lansingh, Mauricio Maia, Wanjiku Mathenge, Sunil Moreker, Mahi M.K. Muqit, Serge Resnikoff, Juan Verdaguer, Peiquan Zhao, Frederick Ferris, Lloyd P. Aiello, Hugh R. Taylor
Diabetes mellitus (DM) is a global epidemic and affects populations in both developing and developed countries, with differing health care and resource levels. Diabetic retinopathy (DR) is a major complication of DM and a leading cause of vision loss in working middle-aged adults. Vision loss from DR can be prevented with broad-level public health strategies, but these need to be tailored to a country’s and population’s resource setting. Designing DR screening programs, with appropriate and timely referral to facilities with trained eye care professionals, and using cost-effective treatment for vision-threatening levels of DR can prevent vision loss. The International Council of Ophthalmology Guidelines for Diabetic Eye Care 2017 summarize and offer a comprehensive guide for DR screening, referral and follow-up schedules for DR, and appropriate management of vision-threatening DR, including diabetic macular edema (DME) and proliferative DR, for countries with high- and low- or intermediate-resource settings. The guidelines include updated evidence on screening and referral criteria, the minimum requirements for a screening vision and retinal examination, follow-up care, and management of DR and DME, including laser photocoagulation and appropriate use of intravitreal anti–vascular endothelial growth factor inhibitors and, in specific situations, intravitreal corticosteroids. Recommendations for management of DR in patients during pregnancy and with concomitant cataract also are included. The guidelines offer suggestions for monitoring outcomes and indicators of success at a population level.
The Relationship of Retinal Vessel Geometric Characteristics to the Incidence and Progression of Diabetic Retinopathy Ophthalmology (IF 8.204) Pub Date : 2018-05-18 Ronald Klein, Kristine E. Lee, Lorraine Danforth, Michael Y. Tsai, Ronald E. Gangnon, Stacy E. Meuer, Tien Y. Wong, Carol Y. Cheung, Barbara E.K. Klein
Purpose To examine the relationships of retinal vessel geometric characteristics (RVGCs) to the incidence and progression of diabetic retinopathy (DR). Design Observational, prospective cohort study. Participants Nine hundred ninety-six persons with type 1 diabetes mellitus (T1DM) and 1370 persons with type 2 diabetes mellitus (T2DM) seen at a baseline examination who were eligible for follow-up examinations at subsequent 5-year intervals. A total of 3846 person-interval data from these follow-up examinations are the basis for the analyses. Methods Diabetic retinopathy and macular edema were assessed by grading of 30° stereoscopic color fundus photographs. Retinal vessel geometric characteristics were assessed using the Singapore I Vessel Assessment program from a digitized copy of 1 of the field 1 fundus photographs obtained at baseline and follow-up. Main Outcome Measures The 5-year incidence of any DR, progression of DR, and incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) in right eyes. Results Incident DR occurred in 45%, progression in 32%, PDR in 10%, and CSME in 5%. While adjusting for glycated hemoglobin, duration of diabetes, and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of any DR (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35). Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; 95% CI, 1.03–1.36), retinal venular curvature tortuosity was associated significantly with the incidence of PDR (OR, 1.15; 95% CI, 1.01–1.30), and retinal venular branching angle (OR, 1.41; 95% CI, 1.10–1.82) was associated significantly with the incidence of CSME. There were no significant associations of other RVGCs with any of the DR outcomes in the full multivariate model. Inclusion of all possible RVGCs did not improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level. Conclusions Retinal vessel geometric characteristics of the retinal venules were associated with progression of DR; however, most of the RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in T1DM and T2DM.
Strabismus, Strabismus Surgery, and Reoperation Rate in the United States : Analysis from the IRIS Registry Ophthalmology (IF 8.204) Pub Date : 2018-05-18 Michael X. Repka, Flora Lum, Bhavya Burugapalli
Purpose To describe the rates of strabismus, strabismus surgery, and strabismus surgery reoperations among all age groups in the United States. Design Retrospective analysis of electronic health record data. Participants Patients from the IRIS (Intelligent Research in Sight) Registry. Methods Description of the types and rates of strabismus and strabismus surgery from 2013 to 2016 with subgroups by age, sex, race/ethnicity, and region of the United States. Main Outcome Measure The 1-year reoperation rate for strabismus surgery performed during 2013–2015 for all age groups. Results A total of 30 827 185 unique patients were identified; 846 477 (2.75%) had a diagnosis of strabismus: 3.02% of male patients and 2.55% of female patients (difference = 0.47%, 95% confidence interval [CI], 0.46–0.48, P < 0.0001). Strabismus surgery was performed in 40 780 (0.13%) unique patients during the 4 years. The rate of surgery ranged from 1.99% for children birth to 5 years of age to 0.05% for adults 40 years of age and older. Horizontal surgical codes were reported 38 813 times, vertical surgery codes were reported 9304 times, and superior oblique codes were reported 711 times. Adjustable sutures were used for 3027 patients (7.42%). Cases with a code for repeat eye muscle surgery or restrictive myopathy were reported for 6098 patients (14.9%). Esotropia accounted for 30.06% and exotropia in 21.77% of diagnoses reported for surgery. The rate of undergoing a reoperation within 1 year of a strabismus surgery was 6.72%, lowest for the group 6 to 9 years of age (3.95%) and increasing with age (P < 0.001) to 11.5% for patients 65 years of age and older. Conclusions Strabismus is an uncommonly reported diagnosis in ophthalmologic practice. Overall, approximately 1 in 750 patients in the IRIS Registry received strabismus surgery (1 in 20 with a strabismus diagnosis) during a 4-year period. Reoperations during the first year after surgery were performed for 1 in 15 patients, increasing with age at surgery. “Big” data from clinical data registries represent real-world care that can be used to develop benchmarks for clinical outcomes and to identify areas for practice improvement and training program design.
Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa Ophthalmology (IF 8.204) Pub Date : 2018-05-11 Yi-Ting Tsai, Wen-Hsuan Wu, Ting-Ting Lee, Wei-Pu Wu, Christine L. Xu, Karen S. Park, Xuan Cui, Sally Justus, Chyuan-Sheng Lin, Ruben Jauregui, Pei-Yin Su, Stephen H. Tsang
PurposeTo develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO).DesignExperimental study for a combination gene therapy that uses both gene ablation and gene replacement.ParticipantsThis study included 2 kinds of human RHO mutation knock-in mouse models: RhoP23H and RhoD190N. In total, 23 RhoP23H/P23H, 43 RhoP23H/+, and 31 RhoD190N/+ mice were used for analysis.MethodsThis study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA.Main Outcome MeasuresElectroretinographic and histologic analysis.ResultsThe thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both RhoP23H and RhoD190N disease models were preserved more significantly using ablate-and-replace gene therapy (P < 0.001), but not by gene replacement monotherapy.ConclusionsAs a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest.
Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia : Systematic Review, Meta-analysis, and Modelling Ophthalmology (IF 8.204) Pub Date : 2018-05-09 Timothy R. Fricke, Nina Tahhan, Serge Resnikoff, Eric Papas, Anthea Burnett, Suit May Ho, Thomas Naduvilath, Kovin S. Naidoo
Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE Ophthalmology (IF 8.204) Pub Date : 2018-05-08 Rahul K. Reddy, Dante J. Pieramici, Shamika Gune, Avanti Ghanekar, Na Lu, Carlos Quezada-Ruiz, Caroline R. Baumal
Purpose To determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients’ potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months. Design Post hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330). Participants Study eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline. Methods To measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest. Main Outcome Measures Baseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24. Results Baseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm. Conclusions Despite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy.
Phenotypic Characteristics of a French Cohort of Patients with X-Linked Retinoschisis Ophthalmology (IF 8.204) Pub Date : 2018-05-05 Raphaëlle Orès, Saddek Mohand-Said, Claire-Marie Dhaenens, Aline Antonio, Christina Zeitz, Edouard Augstburger, Camille Andrieu, José-Alain Sahel, Isabelle Audo
Purpose To analyze the retinal structure in patients with X-linked retinoschisis (XLRS) using spectral-domain OCT and to correlate the morphologic findings with visual acuity, electroretinographic results, and patient age. Design Retrospective, observational study. Participants Data from 52 consecutive male patients with molecularly confirmed XLRS were collected retrospectively. Methods Complete clinical evaluation included best-corrected visual acuity, full-field electroretinography, fundus photography, spectral-domain OCT, and fundus autofluorescence. Spectral-domain OCT images were analyzed to determine full thickness of the retina and tomographic structural changes. Main Outcome Measures Relationships between age, OCT, and visual acuity were assessed. Results One hundred four eyes of 52 patients were included. The mean age at inclusion was 24±15 years (range, 3–57 years). The best-corrected visual acuity ranged from no light perception to 0.1 logarithm of the minimum angle of resolution (mean, 0.6±0.38 logarithm of the minimum angle of resolution). Macular schisis was found in 88% of eyes and macular atrophy was found in 11% of eyes, whereas peripheral schisis was present in 30% of eyes. A spoke-wheel pattern of high and low intensity was the most frequently observed fundus autofluorescence abnormality (51/94 eyes [54%]). The b-to-a amplitude ratio on bright-flash dark-adapted electroretinography was reduced significantly in 45 of 64 eyes (70%). Spectral-domain OCT was available for 97 eyes and showed foveoschisis in 76 of 97 eyes (78%), parafoveal schisis in 10 of 97 eyes (10%), and foveal atrophy in 11 of 97 eyes (11%). Mean central macular thickness (CMT) was of 373.6±140 μm. Cystoid changes were localized mainly in the inner nuclear layer (85/97 eyes [88%]). Qualitative defects in photoreceptor structures were found in most eyes (79/97 eyes [81%]), and the most frequent abnormality was an interruption of the photoreceptor cell outer segment tips (79/79 eyes [100%]). Older age correlated well with lower CMT (correlation coefficient [CC], –0.44; P < 0.001) and with lower photoreceptor outer segment (PROS) length (CC, –0.42; P < 0.001). Lower visual acuity correlated strongly with lower PROS length (CC, –0.53; P < 0.001). Conclusions This study underlined the wide variety of clinical features of XLRS. It highlighted the correlation between visual acuity, patient age, and OCT features, emphasizing the relevance of the latter as potential outcome measure in clinical trials.
Five-Year Graft Survival of Descemet Membrane Endothelial Keratoplasty (EK) versus Descemet Stripping EK and the Effect of Donor Sex Matching Ophthalmology (IF 8.204) Pub Date : 2018-05-03 David A. Price, Meagan Kelley, Francis W. Price Jr., Marianne O. Price
Purpose To determine whether the reduced risk of immunologic rejection with Descemet membrane endothelial keratoplasty (DMEK) results in a 5-year survival advantage relative to Descemet stripping endothelial keratoplasty (DSEK) and to determine whether matching the donor and recipient sex affects the rejection episode and graft survival rates. Design Retrospective cohort study. Participants Patients with Fuchs’ endothelial corneal dystrophy treated with DSEK or DMEK. Methods This study reviewed 2017 consecutive cases (1312 DSEK and 705 DMEK) performed by 13 surgeons between 2003 and 2012 and included the surgeons’ first cases. Survival rates were calculated by Kaplan–Meier analysis. Main Outcome Measures Immunologic rejection episodes, graft failure or replacement for any reason, and endothelial cell loss. Results The 5-year rejection episode rate was lower with DMEK (2.6% vs. 7.9% with DSEK, relative risk, 0.29; 95% confidence interval, 0.16–0.53) despite early reduction of topical corticosteroids in 25% of the DMEK cases. African Americans (n = 46) had a higher risk of rejection episodes than other races (relative risk, 4.4; 95% confidence interval, 2.0–9.6). The cumulative 5-year survival rate was 93% with DSEK and DMEK (P = 0.86). Forty-four DMEK and 69 DSEK grafts failed or were replaced within 5 years, but only 1 DMEK and 4 DSEK failures followed a rejection episode. Rejection episodes increased endothelial cell loss (P = 0.004) but were not a significant risk factor for graft failure within 5 years (P = 0.90). The mean 5-year endothelial cell loss was similar between DMEK (48%±19%) and DSEK (47%±19%) (P = 0.22). Graft rejection episode and survival rates were not significantly influenced by whether the sex of the donor matched that of the recipient (rejection episodes: P = 0.07 for female recipients and P = 0.33 for male recipients; graft survival: P = 0.67 for female recipients and P = 0.17 for male recipients). Conclusions Five-year graft survival was similar between DMEK and DSEK. Although DMEK had a significantly lower risk of immunologic rejection, rejection episodes rarely resulted in graft failure within 5 years with either procedure. Sex matching the donor and recipient provided no survival advantage with DSEK or DMEK.
Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration : A Randomized Clinical Trial Ophthalmology (IF 8.204) Pub Date : 2018-04-30 Philip J. Rosenfeld, Pravin U. Dugel, Frank G. Holz, Jeffrey S. Heier, Joel A. Pearlman, Roger L. Novack, Karl G. Csaky, John M. Koester, Jeffrey K. Gregory, Ryo Kubota
Purpose To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment. Design Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial. Participants Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2 were enrolled. Methods Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25. Main Outcome Measures The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point. Results Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%). Conclusions Emixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug’s mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.
Ultrawide-Field OCT to Investigate Relationships between Myopic Macular Retinoschisis and Posterior Staphyloma Ophthalmology (IF 8.204) Pub Date : 2018-04-30 Kosei Shinohara, Noriko Tanaka, Jost B. Jonas, Noriaki Shimada, Muka Moriyama, Takeshi Yoshida, Kyoko Ohno-Matsui
Purpose To investigate the relationships between myopic macular retinoschisis (MRS) and posterior staphylomas and to reveal the characteristics of other retinal lesions associated with MRS. Design Retrospective, observational case series. Participants Seven hundred twenty-nine eyes of 420 patients with high myopia, which was defined as myopic refractive error of more than –8.0 diopters or an axial length longer than 26.5 mm. Methods Highly myopic eyes were examined by ultrawide-field (UWF) swept-source (SS) OCT with scan width of up to 23 mm and scan depth of 5 mm. The OCT features of MRS and posterior staphylomas and their spatial relationship were examined in UWF SS OCT images. Main Outcome Measures Associations between MRS and staphylomas. Results In 729 eyes with mean axial length of 30.2±2.1 mm, posterior staphyloma was detected in 482 eyes (66.1%) and MRS was detected in 136 eyes (18.7%). All 136 eyes with an MRS showed outer retinoschisis, and 40 eyes (29.4%) also showed inner retinoschisis. Posterior staphyloma was detected significantly more frequently in eyes with MRS (117/136 [86.0%]) than in eyes without MRS (365/593 [61.6%]; P < 0.001). In all eyes with both staphyloma and outer retinoschisis, the area of the outer retinoschisis was restricted to the area within the staphyloma. In 1 of the 19 eyes with outer retinoschisis but without staphyloma, the outer retinoschisis extended beyond the range of the scanned fundus area. Among the 40 eyes with inner retinoschisis, the inner retinoschisis was located within the region of the outer retinoschisis in 39 eyes (97.5%). In all eyes with inner retinoschisis, retinal lesions causing an inward-directed tractional force were found within the area of the inner retinoschisis. Conclusions In highly myopic eyes, the sites of the MRS and staphylomas were spatially related to each other. Posterior-directed force in association with staphylomas, and an inward-directed force resulting from epiretinal membranes or vitreoretinal attachments, may act as causative factors for MRS. However, the exact mechanisms related to the development of an MRS are probably diverse and complex.
Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis Ophthalmology (IF 8.204) Pub Date : 2018-04-30 Jiraporn Jitprapaikulsan, John J. Chen, Eoin P. Flanagan, W. Oliver Tobin, Jim P. Fryer, Brian G. Weinshenker, Andrew McKeon, Vanda A. Lennon, Jacqueline A. Leavitt, Jan-Mendelt Tillema, Claudia Lucchinetti, B. Mark Keegan, Orhun Kantarci, Cheryl Khanna, Sarah M. Jenkins, Grant M. Spears, Jessica Sagan, Sean J. Pittock
Purpose To determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment. Design Cross-sectional cohort study. Participants The study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000–March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing. Methods Serum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG. Main Outcomes Measures Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes. Results Among 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1−positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG−positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG−positive patients, between counting fingers and hand movements in MOG IgG1−positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG−positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1−positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG−positive patients, 22% of idiopathic patients, 12% of MOG IgG1−positive patients, and 8% of MS patients were estimated to have severe visual loss. Conclusions Glial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.
Management of Acute Retinal Ischemia : Follow the Guidelines! Ophthalmology (IF 8.204) Pub Date : 2018-04-30 Valérie Biousse, Fadi Nahab, Nancy J. Newman
Acute retinal arterial ischemia, including vascular transient monocular vision loss (TMVL) and branch (BRAO) and central retinal arterial occlusions (CRAO), are ocular and systemic emergencies requiring immediate diagnosis and treatment. Guidelines recommend the combination of urgent brain magnetic resonance imaging with diffusion-weighted imaging, vascular imaging, and clinical assessment to identify TMVL, BRAO, and CRAO patients at highest risk for recurrent stroke, facilitating early preventive treatments to reduce the risk of subsequent stroke and cardiovascular events. Because the risk of stroke is maximum within the first few days after the onset of visual loss, prompt diagnosis and triage are mandatory. Eye care professionals must make a rapid and accurate diagnosis and recognize the need for timely expert intervention by immediately referring patients with acute retinal arterial ischemia to specialized stroke centers without attempting to perform any further testing themselves. The development of local networks prompting collaboration among optometrists, ophthalmologists, and stroke neurologists should facilitate such evaluations, whether in a rapid-access transient ischemic attack clinic, in an emergency department–observation unit, or with hospitalization, depending on local resources.
Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population Ophthalmology (IF 8.204) Pub Date : 2018-04-30
Purpose To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. Design Cross-sectional meta-analysis. Participants A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3–82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. Methods We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. Main Outcome Measures Determinants of pRNFLT. Results Mean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = –0.38 μm/year; 95% confidence interval [CI], –0.57 to –0.18), higher intraocular pressure (IOP) (β = –0.36 μm/mmHg; 95% CI, –0.56 to –0.15), visual impairment (β = –5.50 μm; 95% CI, –9.37 to –1.64), and history of systemic hypertension (β = –0.54 μm; 95% CI, –1.01 to –0.07) and stroke (β = –1.94 μm; 95% CI, –3.17 to –0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = –3.11 μm; 95% CI, –6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19–1.59) and smoking (β = 1.53 μm; 95% CI, 1.00–2.06 for current smokers compared with never-smokers). Conclusions In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.
Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch’s Membrane Ophthalmology (IF 8.204) Pub Date : 2018-04-26 Jordi Corominas, Johanna M. Colijn, Maartje J. Geerlings, Marc Pauper, Bjorn Bakker, Najaf Amin, Laura Lores Motta, Eveline Kersten, Alejandro Garanto, Joost A.M. Verlouw, Jeroen G.J. van Rooij, Robert Kraaij, Paulus T.V.M. de Jong, Albert Hofman, Johannes R. Vingerling, Tina Schick, Sascha Fauser, Eiko K. de Jong, Cornelia M. van Duijn, Carel B. Hoyng, Caroline C.W. Klaver, Anneke I. den Hollander
Purpose Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants. Design Genome-wide case-control association study of WES data. Participants One thousand one hundred twenty-five AMD patients and 1361 control participants. Methods A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes. Main Outcome Measures Genetic variants associated with AMD. Results We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10–5). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch’s membrane. Conclusions This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch’s membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch’s membrane, contributing to the accumulation of drusen and the development of AMD.
Patterns of Progressive Ganglion Cell–Inner Plexiform Layer Thinning in Glaucoma Detected by OCT Ophthalmology (IF 8.204) Pub Date : 2018-04-25 Joong Won Shin, Kyung Rim Sung, Sun-Won Park
Purpose To investigate the spatial characteristics and patterns of progressive macular ganglion cell–inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Design Longitudinal, retrospective, observational study. Participants Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2–8.1 years) were included. Methods Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Main Outcome Measures Spatial characteristics and patterns of progressive GCIPL thinning. Results Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°–339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. Conclusions The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.
Steroids versus No Steroids in Nonarteritic Anterior Ischemic Optic Neuropathy : A Randomized Controlled Trial Ophthalmology (IF 8.204) Pub Date : 2018-04-25 Rohit Saxena, Digvijay Singh, Medha Sharma, Mathew James, Pradeep Sharma, Vimla Menon
Purpose To examine the role of oral steroid therapy in the treatment of nondiabetic cases of acute nonarteritic anterior ischemic optic neuropathy (NAAION). Design Randomized double-blind clinical trial. Participants Thirty-eight patients with acute nondiabetic NAAION divided into 2 arms of 19 patients each. One arm constituted the cases and the other constituted the controls. Methods Cases received oral steroid therapy and were designated the steroid group, whereas controls received placebo and were designated the nonsteroid group. Best-corrected visual acuity (BCVA), visual evoked response (VER), and OCT were performed at baseline, 1 month, 3 months, and 6 months after recruitment into the trial. Main Outcome Measures Best-corrected visual acuity, VER, and retinal nerve fiber layer changes on OCT. Results Both groups showed significant improvement in BCVA, VER latency, and resolution of disc edema on OCT parameters over 6 months. Final outcome showed no statistically significant difference with regard to visual acuity, although VER was better in the steroid group (P = 0.011). Best-corrected visual acuity, VER amplitude, and VER latency (P = 0.02, P = 0.02, and P = 0.04, respectively) showed a greater percentage improvement in the steroid group, which also saw a faster resolution of disc edema on OCT (1-month follow-up). Conclusions Oral steroids in acute NAAION did not improve the visual acuity significantly at 6 months. However, they improved resolution of disc edema significantly and enabled a greater improvement in VER parameters. This subtle benefit of oral steroids in NAAION is clinically unimportant and does not provide support for its use.
Effects of Prolonged Reading on Dry Eye Ophthalmology (IF 8.204) Pub Date : 2018-04-25 Sezen Karakus, Devika Agrawal, Holly B. Hindman, Claudia Henrich, Pradeep Y. Ramulu, Esen K. Akpek
Purpose To demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters. Design Prospective, observational clinical study. Participants A total of 177 patients with dry eye and 34 normal controls aged 50 years and older. Methods After evaluating symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, the following tests were performed in consecutive order: automated noninvasive tear break-up time (TBUT), surface asymmetry and regularity indices, Schirmer’s testing without anesthesia, corneal staining using fluorescein, and conjunctival staining using lissamine green. The participants were then asked to read a 30-minute validated passage silently. The tests were repeated after the reading task. Main Outcome Measures Changes in tear film and ocular surface parameters after reading. Results All parameters, with the exception of surface asymmetry index, worsened after the reading task in patients with dry eye and in controls. The worsening reached a statistical significance for corneal and conjunctival staining in the dry eye group (P < 0.001) and for corneal staining in the control group (P < 0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P < 0.001). Among postreading measurements, baseline OSDI scores correlated with TBUT (r = −0.15, P = 0.03) in addition to corneal and conjunctival staining (r = 0.25, P < 0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer’s test correlated significantly with their respective baseline values (r = −0.61, P < 0.001 and r = −0.44, P < 0.001), indicating that the more unstable the tear film and the lower the aqueous tear secretion, the worse they became after the prolonged reading task. Worsening in corneal staining directly correlated with the baseline conjunctival staining (r = 0.17, P = 0.02) and surface regularity index (r = 0.21, P = 0.01). Conclusions Evaluating tear film and ocular surface parameters at rest may miss clinical findings brought about by common everyday tasks such as reading, leading to discordance between patient-reported symptoms and clinician-observed signs. Quantifying dry eye after visually straining activities such as prolonged silent reading may help better understand patient symptomatology.
Long-Term Metastatic Risk after Biopsy of Posterior Uveal Melanoma Ophthalmology (IF 8.204) Pub Date : 2018-04-25 Mette Bagger, Isabel Smidt-Nielsen, Mette K. Andersen, Peter K. Jensen, Steffen Heegaard, Klaus K. Andersen, Søren Friis, Jens F. Kiilgaard
Purpose Biopsy of posterior uveal melanoma continues to be intensely debated in terms of the clinical benefits and safety profile. Although several studies have reported a low frequency of ocular complications after tumor biopsy, the potential long-term risk of iatrogenic dissemination remains unresolved. The purpose of this study was to assess the risk of metastatic disease after biopsy of posterior uveal melanoma. Design Retrospective nationwide cohort study linking clinical and histopathologic records to pathology, cancer, and mortality registries. Participants All patients with posterior uveal melanoma treated in Denmark between January 1985 and December 2016. Methods For each patient, we recorded detailed information on age, gender, tumor characteristics, and diagnostic and therapeutic measures, including tumor biopsy, if any, and the primary treating hospital. Absolute risk of melanoma-specific death was presented by cumulative incidence curves that accounted for competing risks. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and melanoma-specific mortality of patients who underwent biopsy during primary treatment compared with nonbiopsied patients through November 1, 2017. Fine and Gray risk regression was used as a sensitivity analysis to evaluate the impact of competing risks. Main Outcome Measures All-cause and melanoma-specific mortality. Results Among 1637 patients, 567 (35%) underwent biopsy during primary treatment. At diagnosis, biopsied patients exhibited better prognostic characteristics, including smaller tumor size (P < 0.001) and younger age (P < 0.001), than nonbiopsied patients. In the adjusted analyses, we observed no apparent differences in all-cause mortality (HR, 1.07; 95% CI, 0.89–1.26; P = 0.47) or melanoma-specific mortality (HR, 1.11; 95% CI, 0.89–1.39; P = 0.35) among biopsied patients compared with nonbiopsied patients. Conclusions All-cause and melanoma-specific mortality after primary treatment were similar among biopsied and nonbiopsied patients with posterior uveal melanoma. Our findings do not support an increased metastatic risk after intraocular tumor biopsy.
A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography Ophthalmology (IF 8.204) Pub Date : 2018-04-10 Felix Grassmann, Judith Mengelkamp, Caroline Brandl, Sebastian Harsch, Martina E. Zimmermann, Birgit Linkohr, Annette Peters, Iris M. Heid, Christoph Palm, Bernhard H.F. Weber
Purpose Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Design Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. Participants We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. Methods We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. Main Outcome Measures κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. Results A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%–92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly. Conclusions Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age.
Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light : Clinical Characteristics Ophthalmology (IF 8.204) Pub Date : 2018-04-04 Joseph T. Hull, Charles A. Czeisler, Steven W. Lockley
Purpose Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Design Within-subject, dark-controlled design. Participants A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation = 49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Methods Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (∼7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4 lux) conditions. Main Outcome Measures Area under the curve (AUC) for melatonin concentration. Results Melatonin concentrations were significantly suppressed (defined as ≥33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n = 2; retinopathy of prematurity [ROP], n = 2; bilateral retinal detachments, n = 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n = 3; optic neuritis/neuropathy, n = 2; retinopathy unknown, n = 2; congenital glaucoma, n = 1; congenital rubella syndrome, n = 1; measles retinopathy, n = 1) and in all 3 bilaterally enucleated participants. Conclusions These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness.
Choroidal and Sub-Retinal Pigment Epithelium Caverns : Multimodal Imaging and Correspondence with Friedman Lipid Globules Ophthalmology (IF 8.204) Pub Date : 2018-04-04 Rosa Dolz-Marco, Jay P. Glover, Orly Gal-Or, Katie M. Litts, Jeffrey D. Messinger, Yuhua Zhang, Mariano Cozzi, Marco Pellegrini, K. Bailey Freund, Giovanni Staurenghi, Christine A. Curcio
Purpose To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. Design Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. Participants Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). Methods Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. Main Outcome Measures Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. Results Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. Conclusions Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.
Gaze-Evoked Deformations in Optic Nerve Head Drusen : Repetitive Shearing as a Potential Factor in the Visual and Vascular Complications Ophthalmology (IF 8.204) Pub Date : 2018-04-02 Patrick A. Sibony, Junchao Wei, Ian A. Sigal
Purpose To determine if ocular ductions deform intrapapillary and peripapillary tissues in optic nerve head drusen (ONHD) and to compare these deformations with healthy eyes and eyes with other optic neuropathies. Design Observational case series. Participants Twenty patients with ONHD. Methods Axial rasters of the optic nerve from a spectral-domain OCT device (Cirrus 5000; Carl Zeiss Meditec, Inc, Dublin, CA) were used to analyze the shape of the peripapillary basement membrane (ppBM) layer in 20 confirmed cases of ONHD. We compared registered images obtained from 2 eye positions: 10° to 15° in adduction and 30° to 40° in abduction. Geometric morphometrics was used to analyze the shape of the ppBM layer defined by placing 10 equidistant landmarks extending 2500 μm on both sides of the basement membrane opening. We also adapted an image strain tracking technique to measure regional intrapapillary strains in 6 patients. Using manually placed nodes on the reference image (in adduction), an iterative, block-matching algorithm is used to determine local displacements between the reference and its paired image in abduction. Displacement vectors were used to calculate the mean shear and effective strain (percent change). Main Outcome Measures Peripapillary shape deformations, intrapapillary shear strains, and effective strains. Results We found a statistically significant difference in the shape of the ppBM layer between abduction and adduction (P < 0.01). The deformation was characterized by a relative posterior displacement temporally in adduction that reversed in abduction. Strain tracking in all 6 patients showed substantial gaze-induced shearing and effective strains. Mean effective strains were 7.5% outside the drusen. Shear and effective strains were significantly larger outside versus within the drusen (P < 0.003 and P < 0.01, respectively). Conclusions This study demonstrates that horizontal ocular ductions induce significant shearing deformations of the peripapillary retina and prelaminar intrapapillary tissues. We also found that the deformations in healthy persons are similar in magnitude to ONHD. Based on these findings, we speculate that patients with intrapapillary calcifications exposed to the long-term effects of repetitive shearing (induced by ocular ductions) may contribute to the progressive axonal loss and vascular complications associated with ONHD.
The Globe’s Eccentric Rotational Axis : Why Medial Rectus Surgery Is More Potent than Lateral Rectus Surgery Ophthalmology (IF 8.204) Pub Date : 2018-03-30 Robert A. Clark, Joseph L. Demer
Purpose Tables typically recommend greater lateral rectus (LR) than medial rectus (MR) surgical doses for horizontal strabismus of any given magnitude, a difference unexplained by mechanical models that assume globe rotation about its center. We tested this assumption during horizontal ductions. Design Prospective observational study. Participants Eighteen adult subjects with normal binocular vision. Methods Surface coil magnetic resonance imaging at 390 or 430 μm resolution was obtained using 2-mm–thick contiguous axial planes while subjects fixated targets in central, right, and left gaze. Angular displacements of lines connecting the corneal apex through the minor lens axis to the retina were measured to approximate clinical ductions. Globe centers were calculated from their area centroids. Apparent lens and globe-optic nerve (ON) junction rotations around the globe center were then compared with clinical ductions. Main Outcome Measures Apparent angular rotations of lenses and globe-ON junctions during horizontal ductions. Results Globe-ON junctions appeared to rotate significantly less around globe centers than did lenses for abduction (20.6°±4.7° vs. 27.4°±7.4°, ± standard deviation (SD), P < 0.001) and adduction (25.3°±6.7° vs. 31.9°±8.3°, P < 0.001). Both rotations differed significantly from clinical adduction (27.9°±8.3°, P < 0.007), but only in abduction was globe-ON junction rotation significantly less than clinical abduction (28.6°±9.4°, P < 0.001). The true geometric globe rotational center was 2.2±0.5 mm medial and 0.8±1.0 mm posterior to the geometric globe center and was displaced farther medially and posteriorly during adduction. This eccentricity imbues each millimeter of MR recession with approximately 30% more trigonometric rotational effect than equivalent LR recession. Conclusions The medial and posterior eccentricities of the normal ocular rotational axis profoundly influence horizontal rectus action. The proximity of the globe’s rotational axis to the MR shortens its lever arm relative to the LR, explaining why mechanical effects of smaller MR recessions are equivalent to larger LR recessions.
Loss to Follow-Up in Patients with Proliferative Diabetic Retinopathy after Panretinal Photocoagulation or Intravitreal Anti-VEGF Injections Ophthalmology (IF 8.204) Pub Date : 2018-03-29 Anthony Obeid, Xinxiao Gao, Ferhina S. Ali, Katherine E. Talcott, Christopher M. Aderman, Leslie Hyman, Allen C. Ho, Jason Hsu
Purpose Loss to follow-up (LTFU) may contribute to vision loss in patients with active proliferative diabetic retinopathy (PDR). The aim of this study is to determine and compare the rates of LTFU in patients with PDR receiving panretinal photocoagulation (PRP) or intravitreal injections (IVIs) with anti-vascular endothelial growth factor (VEGF) over approximately 4 years. Moreover, this study evaluates various risk factors for LTFU. Design Retrospective cohort study. Participants A total of 2302 patients with PDR receiving IVIs with anti-VEGF or PRP between January 1, 2012, and April 20, 2016. Methods Intervals between each procedure and the subsequent follow-up visit were measured. Loss to follow-up was defined as at least 1 interval exceeding 12 months duration. Main Outcome Measures The LTFU rates and associated risk factors. Results A total of 1718 patients (74.6%) followed up postprocedure and 584 patients (25.4%) were LTFU over approximately 4 years. Of the patients receiving PRP, 28.0% were LTFU compared with 22.1% of patients receiving IVI with anti-VEGF (P = 0.001). The LTFU rates decreased as age increased, with rates of 28.1% for patients aged ≤55 years, 27.0% for patients aged 56 to 65 years, and 20.9% for patients aged >65 years (P = 0.002). Loss to follow-up also differed by race, with rates of 19.4% for whites, 30.2% for African Americans, 19.7% for Asians, 38.0% for Hispanics, Native Americans, and Pacific Islanders, and 34.9% for patients of unreported race (P < 0.001). The LTFU rates also increased as regional average adjusted gross incomes (AGIs) decreased, with rates of 33.9% for patients with regional average AGI of ≤$40 000, 24.0% for patients with regional average AGI from $41 000 to $80 000, and 19.7% for patients with regional average AGI >$80 000 (P < 0.001). Procedure type, age, race, and regional average AGI were all significant (P < 0.05) independent risk factors of LTFU in the multivariate regression. Conclusions A large proportion of patients with PDR were LTFU after receiving PRP or an anti-VEGF injection over approximately 4 years. Key risk factors included age, race, and regional average AGI.
Cost Evaluation of Early Vitrectomy versus Panretinal Photocoagulation and Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy Ophthalmology (IF 8.204) Pub Date : 2018-03-29 James Lin, Jonathan S. Chang, Nicolas A. Yannuzzi, William E. Smiddy
Purpose To evaluate costs and cost-utility of early vitrectomy (pars plana vitrectomy [PPV]) compared with panretinal photocoagulation (PRP) and intravitreal ranibizumab (IVR) for proliferative diabetic retinopathy (PDR) without diabetic macular edema. Design A decision analysis model of cost-utility. Participants There were no participants. Methods A decision analysis was based on results from the Diabetic Retinopathy Clinical Research Network Protocol S comparing treatment of PRP with IVR (0.3 mg) in PDR without incident macular edema to model the total 2-year costs and outcomes for each treatment scenario. These values were compared with the 2-year hypothetical costs of early PPV for PDR. Centers for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital/facility-based and nonfacility setting. Cost-utility was calculated on the basis of the preserved visual utility and estimated life years remaining. In addition, costs for lifetime treatment were modeled for all scenarios and used to calculate lifetime quality-adjusted life years (QALY) costs for each scenario. Sensitivity analyses were performed to evaluate the impact of the model’s assumptions. Main Outcome Measures Cost of treatment, utility, and cost per QALY. Results The modeled cost per QALY of treatment for PDR for 2 years of utility in the facility (nonfacility) setting was $163 988 ($102 559) in the PRP group, $436 992 ($326 424) in the IVR group, and $181 144 ($107 965) in the PPV group. Sensitivity analysis showed that both IVR and PPV groups would have equivalent costs per QALY over the first 2 years if 78% (facility) and 80% (nonfacility) of patients in the PPV group required additional treatment with IVR (at the dose of 10.1 injections as in Protocol S). Beyond 2 years, the cost per QALY in the facility (nonfacility) setting was calculated as $61 695 ($21 752) in the PRP group, $338 348 ($239 741) in the IVR group, and $63 942 ($22 261) in the PPV group. Conclusions Early PPV as a strategy for treatment of PDR without macular edema demonstrates cost-utility similar to management with PRP and more favorable cost-utility compared with IVR in the short term. This advantage over IVR continues when lifetime costs are factored.
Evaluation of Ophthalmic Surgical Instrument Sterility Using Short-Cycle Sterilization for Sequential Same-Day Use Ophthalmology (IF 8.204) Pub Date : 2018-03-27 David F. Chang, Nikki Hurley, Nick Mamalis, Jeffrey Whitman
Purpose The common practice of short-cycle sterilization for ophthalmic surgical instrumentation has come under increased regulatory scrutiny. This study was undertaken to evaluate the efficacy of short-cycle sterilization processing for consecutive same-day cataract procedures. Design Testing of specific sterilization processing methods by an independent medical device validation testing laboratory. Participants Phaco handpieces from 3 separate manufacturers were tested along with appropriate biologic indicators and controls using 2 common steam sterilizers. Methods A STATIM 2000 sterilizer (SciCan, Canonsburg, PA) with the STATIM metal cassette, and an AMSCO Century V116 pre-vacuum sterilizer (STERIS, Mentor, OH) using a Case Medical SteriTite container (Case Medical, South Hackensack, NJ) rigid container were tested using phaco tips and handpieces from 3 different manufacturers. Biological indicators were inoculated with highly resistant Geobacillus stearothermophilus, and each sterility verification test was performed in triplicate. Both wrapped and contained loads were tested with full dry cycles and a 7-day storage time to simulate prolonged storage. In adherence with the manufacturers’ instructions for use (IFU), short cycles (3.0–3.5-minute exposure times) for unwrapped and contained loads were also tested after only 1 minute of dry time to simulate use on a consecutive case. Additional studies were performed to demonstrate whether any moisture present in the load containing phaco handpieces postprocessing was sterile and would affect the sterility of the contents after a 3-minute transit/storage time. This approximated the upper limit of time needed to transfer a containment device to the operating room. Main Outcome Measures Presence or absence of microbial growth from cultured test samples. Results All inoculated test samples from both sterilizers were negative for growth of the target organism whether the full dry phase was interrupted or not. Pipetted postprocessing moisture samples and swabs of the handpieces were also negative for growth after a 3-minute transit/storage time. Conclusions These studies support the use of unwrapped, short-cycle sterilization that adheres to the IFU of these 2 popular Food and Drug Administration–cleared sterilizers for sequential same-day cataract surgeries. A full drying phase is not necessary when the instruments are kept within the covered sterilizer containment device for prompt use on a sequential case.
Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease Ophthalmology (IF 8.204) Pub Date : 2018-03-27 José Luis Martín-Varillas, Vanesa Calvo-Río, Emma Beltrán, Juan Sánchez-Bursón, Marina Mesquida, Alfredo Adán, María Victoria Hernandez, Marisa Hernández Garfella, Elia Valls Pascual, Lucía Martínez-Costa, Agustí Sellas-Fernández, Miguel Cordero-Coma, Manuel Díaz-Llopis, Roberto Gallego, David Salom, Norberto Ortego, José L. García-Serrano, José-Luis Callejas-Rubio, José M. Herreras, Ángel García-Aparicio, Olga Maíz, Ana Blanco, Ignacio Torre, David Díaz-Valle, Esperanza Pato, Elena Aurrecoechea, Miguel A. Caracuel, Fernando Gamero, Enrique Minguez, Carmen Carrasco-Cubero, Alejandro Olive, Julio Vázquez, Oscar Ruiz-Moreno, Javier Manero, Santiago Muñoz-Fernández, Myriam Gandía Martinez, Esteban Rubio-Romero, F. Javier Toyos-Sáenz de Miera, Francisco Javier López Longo, Joan M. Nolla, Marcelino Revenga, Carmen González-Vela, Javier Loricera, Belén Atienza-Mateo, Rosalía Demetrio-Pablo, José Luis Hernández, Miguel A. González-Gay, Ricardo Blanco
Purpose To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. Design Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Subjects Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3–12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. Methods After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Main Outcome Measures Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. Results No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). Conclusion ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.
Determinants of Outcomes of Adenoviral Keratoconjunctivitis Ophthalmology (IF 8.204) Pub Date : 2018-03-27
Purpose To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. Design Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). Participants Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. Methods Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. Main Outcome Measures The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. Results Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non–adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. Conclusions A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non–adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.
Ten-Year Progression of Myopic Maculopathy : The Beijing Eye Study 2001–2011 Ophthalmology (IF 8.204) Pub Date : 2018-03-27 Yan Ni Yan, Ya Xing Wang, Yan Yang, Liang Xu, Jie Xu, Qian Wang, Jing Yan Yang, Xuan Yang, Wen Jia Zhou, Kyoko Ohno-Matsui, Wen Bin Wei, Jost B. Jonas
Purpose To investigate the progression pattern of myopic maculopathy and associated factors in a population-based study. Design Population-based longitudinal study. Participants The Beijing Eye Study including 4439 participants in 2001 was repeated in 2011, with 2695 individuals (66.4%) being re-examined in 2011. Methods The study participants underwent detailed ophthalmic and general examinations. Using fundus photographs obtained in 2001 and 2011, we assessed the progression of myopic maculopathy in highly myopic eyes with a refractive error ≥−6 diopters in 2001. Myopic maculopathy was differentiated into tessellated fundus (category 1), diffuse chorioretinal atrophy (category 2), patchy chorioretinal atrophy (category 3), and macular atrophy (category 4), with lacquer cracks and choroidal neovascularization as additional plus signs. Main Outcome Measures Progression pattern of myopic maculopathy. Results Of 110 highly myopic eyes (70 individuals) at baseline, 39 eyes (35.5%) showed progression observed in 15 of 79 eyes (19%) with tessellated fundus at baseline, in 17 of 24 eyes (71%) with diffuse chorioretinal atrophy, in all 6 eyes with patchy chorioretinal atrophy, and the 1 eye with macular atrophy. Lacquer cracks detected in 2 eyes in 2001 developed into a small patchy atrophy (1 eye) or widened during the follow-up (1 eye). Five eyes demonstrated new lacquer cracks. In binary regression analysis, progression of myopic maculopathy was associated with longer axial length (P < 0.001; odds ratio [OR], 7.13; 95% confidence interval [CI], 2.49–20.4), older age (P = 0.001; OR, 1.25; 95% CI, 1.10–1.42), higher prevalence of staphylomas (P = 0.03; OR, 24.3; 95% CI, 2.89–204), smaller parapapillary γ-zone in 2011 (P = 0.01; OR, 0.61; 95% CI, 0.41–0.91), and female gender (P = 0.04; OR, 9.78; 95% CI, 1.06–90.6). Conclusions The 10-year progression rate of myopic maculopathy in this elderly Chinese population was 35.5%, increasing from 15 of 79 eyes (19%) in category 1 of myopic maculopathy at baseline to 17 of 24 eyes (71%) in category 2 and 6 of 6 eyes (100%) in category 3. Risk factors for myopic maculopathy progression were longer axial length, pre-existing staphylomata, smaller parapapillary γ-zone, older age, and female gender.
Retinal Degeneration in Choroideremia follows an Exponential Decay Function Ophthalmology (IF 8.204) Pub Date : 2018-03-23 James W. Aylward, Kanmin Xue, Maria I. Patrício, Jasleen K. Jolly, Jonathan C. Wood, Jonathan Brett, Kirti M. Jasani, Robert E. MacLaren
Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma Ophthalmology (IF 8.204) Pub Date : 2018-03-21 Raymond P. Najjar, Sourabh Sharma, Eray Atalay, Annadata V. Rukmini, Christopher Sun, Jing Zhan Lock, Mani Baskaran, Shamira A. Perera, Rahat Husain, Ecosse Lamoureux, Joshua J. Gooley, Tin Aung, Dan Milea
Purpose To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. Design Cross-sectional study. Participants Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of −6 decibels or better on automated perimetry. Methods Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. Main Outcome Measures Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson’s correlation analysis. Results Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. Conclusions Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.
Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific Functioning Ophthalmology (IF 8.204) Pub Date : 2018-03-20 Preeti Gupta, Alfred Tau Liang Gan, Ryan Eyn Kidd Man, Eva K. Fenwick, Neelam Kumari, Gavin Tan, Paul Mitchell, Charumathi Sabanayagam, Tien Yin Wong, Ching-Yu Cheng, Ecosse L. Lamoureux
Purpose To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). Design Population-based cohort study. Participants A total of 518 participants aged 40 to 80 years (baseline visit 2007–2009 and second visit 6 years later, 2013–2015), with diabetes, clinical data, and VF information at both visits. Main Outcome Measures VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. Methods Incident DR was defined using the Modified Airlie House classification as “none or minimal” DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. Results Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (β = −0.60; 95% confidence interval [CI], −0.96 to −0.24; P = 0.001) and 23% (β = −1.00; 95% CI, −1.61 to −0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (β = −0.18; 95% CI, −1.00, 0.64; P = 0.660). Conclusions Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR.
Clinical Prediction Performance of Glaucoma Progression Using a 2-Dimensional Continuous-Time Hidden Markov Model with Structural and Functional Measurements Ophthalmology (IF 8.204) Pub Date : 2018-03-20 Youngseok Song, Hiroshi Ishikawa, Mengfei Wu, Yu-Ying Liu, Katie A. Lucy, Fabio Lavinsky, Mengling Liu, Gadi Wollstein, Joel S. Schuman
Purpose Previously, we introduced a state-based 2-dimensional continuous-time hidden Markov model (2D CT HMM) to model the pattern of detected glaucoma changes using structural and functional information simultaneously. The purpose of this study was to evaluate the detected glaucoma change prediction performance of the model in a real clinical setting using a retrospective longitudinal dataset. Design Longitudinal, retrospective study. Participants One hundred thirty-four eyes from 134 participants diagnosed with glaucoma or as glaucoma suspects (average follow-up, 4.4±1.2 years; average number of visits, 7.1±1.8). Methods A 2D CT HMM model was trained using OCT (Cirrus HD-OCT; Zeiss, Dublin, CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI) or mean deviation (MD; Humphrey Field Analyzer; Zeiss). The model was trained using a subset of the data (107 of 134 eyes [80%]) including all visits except for the last visit, which was used to test the prediction performance (training set). Additionally, the remaining 27 eyes were used for secondary performance testing as an independent group (validation set). The 2D CT HMM predicts 1 of 4 possible detected state changes based on 1 input state. Main Outcome Measures Prediction accuracy was assessed as the percentage of correct prediction against the patient's actual recorded state. In addition, deviations of the predicted long-term detected change paths from the actual detected change paths were measured. Results Baseline mean ± standard deviation age was 61.9±11.4 years, VFI was 90.7±17.4, MD was −3.50±6.04 dB, and cRNFL thickness was 74.9±12.2 μm. The accuracy of detected glaucoma change prediction using the training set was comparable with the validation set (57.0% and 68.0%, respectively). Prediction deviation from the actual detected change path showed stability throughout patient follow-up. Conclusions The 2D CT HMM demonstrated promising prediction performance in detecting glaucoma change performance in a simulated clinical setting using an independent cohort. The 2D CT HMM allows information from just 1 visit to predict at least 5 subsequent visits with similar performance.
Blue Nevi of the Ocular Surface : Clinical Characteristics, Pathologic Features, and Clinical Course Ophthalmology (IF 8.204) Pub Date : 2018-03-15 Ibrahim Sayed-Ahmed, Juan Carlos Murillo, Pedro Monsalve, Jan Paul Ulloa, Maria P. Fernandez, James Wong, George Elgart, Anat Galor, Sander R. Dubovy, Carol L. Karp
Purpose Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva. Design Retrospective, noncomparative case series. Participants Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016. Methods Chart review of patients identified from a database search of the Florida Lions Ocular Pathology Laboratory records. Pathologic diagnoses were confirmed by 2 pathologists (S.R.D. and G.E.). All specimens were bleached and, tissue permitting, stained using SOX10 (MilliporeSigma, Darmstadt, Germany) and CD68 (Leica Biosystems, Nussloch, Germany). Main Outcome Measures Clinical characteristics, pathologic features, and clinical course. Results Mean age of the population was 55±15 years; 71.4% (n = 15) were white and 57.1% (n = 12) were men. One patient had 3 lesions, for a total of 23 lesions examined. Clinically, 13 lesions were on the bulbar conjunctiva, 3 were on the tarsal conjunctiva, 3 were in the fornix, 2 were caruncular, 1 was episcleral, and 1 was at the limbus. Before excision, 8 patients were thought to have primary acquired melanosis, 4 with concern for primary conjunctival melanoma, and 1 thought to have metastatic disease from a plantar melanoma. Five lesions were thought to be benign, and in 8 patients, the lesions were identified incidentally after other ocular surgeries, with no diagnosis of the lesions before excision. Pathologic features were consistent with simple blue nevi in 21 lesions and cellular blue nevus in 2 lesions. No malignant transformations were noted in any patient over the mean 20.2-month follow-up period (range, 2 weeks–103 months). Conclusions Blue nevus is a rare deeply pigmented congenital melanocytic lesion with a benign clinical course that can appear clinically similar to primary acquired melanosis or melanoma.
Incidence, Risk Factors, and Management of Blindness after Orbital Surgery Ophthalmology (IF 8.204) Pub Date : 2018-03-15 Sarah M. Jacobs, Colin P. McInnis, Matthew Kapeles, Shu-Hong Chang
Purpose Severe vision loss is a risk of orbital surgery which physicians should counsel patients about, but the overall risk rate is unknown. This research was conducted to determine the risk of severe vision loss related to orbital surgery. Design Retrospective review. Participants Patients who underwent orbital surgery at either of 2 academic medical centers between January 1994 and December 2014. Methods A billing database search was conducted to identify all patients who had orbital surgery during the study period, cross-checked against diagnostic codes related to vision loss. Charts were screened to determine baseline demographic and medical history, surgical procedure, intraoperative and perioperative management, and visual acuity. Patients with preoperative visual acuity ≥20/200 that worsened ≤20/400 after orbital surgery were included for detailed review. Statistical analysis was conducted to identify factors posing particular risk or benefit to visual outcome in these patients. Main Outcome Measures Visual acuity after orbital surgery. Results A total of 1665 patients underwent orbital surgery during the inclusion period, with 14 patients sustaining severe vision loss ranging from counting fingers at 1 foot to no light perception (overall risk, 0.84%). The causes of vision loss included retrobulbar hemorrhage, malpositioned implant, optic nerve ischemia, or direct optic nerve insult. When stratified by surgical approach, the risk of a blinding surgical complication was significantly higher for patients undergoing orbital floor repair in the setting of multiple facial fractures (subgroup risk, 6.45%), bony decompression of the optic canal (subgroup risk, 15.6%), or intracranial approach to the orbital roof (subgroup risk, 18.2%). Seven of 8 patients with a potentially reversible cause of postoperative vision loss underwent urgent repeat surgery, and 2 regained substantial vision (20/20 and 20/25). Administration of intravenous corticosteroids had no significant effect on visual acuity outcome. Conclusions The overall risk of severe vision loss after orbital surgery is 0.84%. The subgroup risk is higher in patients undergoing facial polytrauma repair, optic canal decompression, or orbital apex surgery from an intracranial approach. Close postoperative monitoring and urgent assessment and management of acute vision loss may improve visual outcome in some patients.
Longitudinal Changes of Optic Nerve Head and Peripapillary Structure during Childhood Myopia Progression on OCT : Boramae Myopia Cohort Study Report 1 Ophthalmology (IF 8.204) Pub Date : 2018-03-14 Martha Kim, Ho-Kyung Choung, Kyoung Min Lee, Sohee Oh, Seok Hwan Kim
Purpose To delineate longitudinal changes in the optic nerve head (ONH) and peripapillary structure during myopia progression in childhood using spectral-domain (SD) OCT and to explore the factors associated with myopic ONH and peripapillary changes. Design Prospective cohort study. Participants Twenty-three healthy children with myopia (46 eyes). Methods The participants underwent fundus photography, SD OCT, and axial length (AXL) measurements every 6 months for 2 years. Based on the morphologic changes of the ONH and β-zone parapapillary atrophy (PPA), eyes were classified as group A (ONH unchanged without β-zone PPA; 11 eyes), group B (ONH changed without β-zone PPA at baseline; 10 eyes), group C (ONH changed with β-zone PPA at baseline; 15 eyes), and group D (ONH unchanged with β-zone PPA; 10 eyes). The configuration of the border tissue (BT) at the temporal margin of the ONH was assessed, and the ONH parameters, including Bruch's membrane opening distance (BMOD), border length (BL), and BT angle (BTA), were measured on horizontal SD OCT scans. Main Outcome Measures Changes in ONH parameters and associated factors. Results Group B showed the greatest AXL increase per year (group B > group C > group A = group D; P < 0.001). During the follow-up periods, the BT configuration initially was changed from internally oblique to externally oblique (group B) and was stretched, resulting in optic disc ovality and γ-zone PPA development (group C). In group C, BL was increased significantly nasally and BTA was decreased significantly, whereas BMOD remained stable (P < 0.001, P < 0.001, and P = 0.100, respectively). In the multivariate analysis using the generalized linear mixed-effect model, the changes of BL and BTA were associated with axial elongation (P = 0.028 and P = 0.010, respectively). Conclusions Development of myopic optic disc and γ-zone PPA during myopia progression was delineated using SD OCT images. During the ONH and peripapillary changes, the BL was increased nasally and the BTA was decreased, whereas the BMOD remained relatively stable. The association of axial elongation with ONH and peripapillary tissue changes may facilitate understanding of the relationship between myopia and glaucoma.
Grader Variability and the Importance of Reference Standards for Evaluating Machine Learning Models for Diabetic Retinopathy Ophthalmology (IF 8.204) Pub Date : 2018-03-13 Jonathan Krause, Varun Gulshan, Ehsan Rahimy, Peter Karth, Kasumi Widner, Greg S. Corrado, Lily Peng, Dale R. Webster
Purpose Use adjudication to quantify errors in diabetic retinopathy (DR) grading based on individual graders and majority decision, and to train an improved automated algorithm for DR grading. Design Retrospective analysis. Participants Retinal fundus images from DR screening programs. Methods Images were each graded by the algorithm, U.S. board-certified ophthalmologists, and retinal specialists. The adjudicated consensus of the retinal specialists served as the reference standard. Main Outcome Measures For agreement between different graders as well as between the graders and the algorithm, we measured the (quadratic-weighted) kappa score. To compare the performance of different forms of manual grading and the algorithm for various DR severity cutoffs (e.g., mild or worse DR, moderate or worse DR), we measured area under the curve (AUC), sensitivity, and specificity. Results Of the 193 discrepancies between adjudication by retinal specialists and majority decision of ophthalmologists, the most common were missing microaneurysm (MAs) (36%), artifacts (20%), and misclassified hemorrhages (16%). Relative to the reference standard, the kappa for individual retinal specialists, ophthalmologists, and algorithm ranged from 0.82 to 0.91, 0.80 to 0.84, and 0.84, respectively. For moderate or worse DR, the majority decision of ophthalmologists had a sensitivity of 0.838 and specificity of 0.981. The algorithm had a sensitivity of 0.971, specificity of 0.923, and AUC of 0.986. For mild or worse DR, the algorithm had a sensitivity of 0.970, specificity of 0.917, and AUC of 0.986. By using a small number of adjudicated consensus grades as a tuning dataset and higher-resolution images as input, the algorithm improved in AUC from 0.934 to 0.986 for moderate or worse DR. Conclusions Adjudication reduces the errors in DR grading. A small set of adjudicated DR grades allows substantial improvements in algorithm performance. The resulting algorithm's performance was on par with that of individual U.S. Board-Certified ophthalmologists and retinal specialists.
Correlation of Corneal and Scleral Pneumatonometry in Pediatric Patients Ophthalmology (IF 8.204) Pub Date : 2018-03-12 Jun Hui Lee, Lucia Rivera Sanchez, Travis Porco, Ying Han, Alejandra G. de Alba Campomanes
Purpose To study the correlation between corneal and scleral intraocular pressure (IOP) by pneumatonometry in pediatric patients. Design Cross-sectional study. Participants Patients (age range, 0–15 years) undergoing an eye examination under anesthesia or eye surgery were recruited at the University of California, San Francisco, Benioff Children's Hospital between July 2015 and April 2016. Methods Intraocular pressure measurements were obtained by pneumatonometry on the central cornea and the inferonasal and inferotemporal sclera in a random order. Spearman correlations between corneal versus inferonasal scleral IOP and corneal versus inferotemporal scleral IOP were calculated. A linear mixed-effect model was used to derive a predictive equation for corneal IOP from scleral IOP and to perform covariate analysis for age, axial length, central corneal thickness, and lens status. The standard deviation of the predicted corneal IOP was determined by bootstrap mixed-effect regression analysis. Main Outcome Measures The predictive model of corneal IOP from scleral IOP. Results Seventy-five eyes from 40 patients were included in the study. Spearman correlation coefficient for corneal versus inferotemporal scleral IOP was 0.79 (P < 0.01) and 0.48 for corneal versus inferonasal scleral IOP (P < 0.01). Corneal IOP may be predicted from scleral IOP via the following equations: corneal IOP = 0.73 × inferotemporal scleral IOP + 7.45 and corneal IOP = 0.21 × inferonasal scleral IOP + 17.83. Central corneal thickness (P = 0.07), lens status (P = 0.4), age (P = 0.33), and axial length (P = 0.15) did not affect significantly the relationship between corneal and scleral IOP in the multivariate regression analysis. The standard deviation of predicted corneal IOP was less than 1.2 mmHg within an inferotemporal scleral IOP range of 10 to 35 mmHg. Conclusions In children, corneal and scleral IOP are correlated significantly when measured by pneumatonometry. Measurements obtained from the inferotemporal sclera are better predictors of corneal IOP than those obtained from inferonasal sclera. Pneumatonometry on the inferotemporal sclera may be an alternative method to estimate IOP for pediatric patients from whom corneal IOP measurement is difficult to obtain.
Positional Change of Optic Nerve Head Vasculature during Axial Elongation as Evidence of Lamina Cribrosa Shifting : Boramae Myopia Cohort Study Report 2 Ophthalmology (IF 8.204) Pub Date : 2018-03-12 Kyoung Min Lee, Ho-Kyung Choung, Martha Kim, Sohee Oh, Seok Hwan Kim
Purpose To investigate the positional change of central retinal vasculature and vascular trunk to deduce the change in the lamina cribrosa (LC) during axial elongation. Design Prospective cohort study. Participants Twenty-three healthy myopic children (46 eyes). Methods Participants had undergone a full ophthalmologic examination and axial length measurement every 6 months for 2 years. Using spectral-domain OCT, circle scans centered around the optic disc in the glaucoma progression analysis mode, which enabled capturing of the same positions throughout the entire study period, and enhanced depth imaging of the deep optic nerve head complex were performed. Infrared imaging of the circle scans was used to measure the changes in the angles between the first and final visits. The angle between the major superior and inferior retinal arteries was measured along the circle scan twice: from the center of the circle scan and from the central retinal vascular trunk, respectively. The positional change of the retinal vascular trunk also was measured. Main Outcome Measures Change in vascular angle and position of vascular trunk with axial elongation and associated factors. Results The vascular angle measured from the center of the circle scan did not change (P = 0.247), whereas the angle measured from the central retinal arterial trunk decreased with axial elongation (P < 0.001). A generalized estimating equation analysis revealed that the factors associated with angle decrease were axial elongation (P = 0.004) and vascular trunk dragging (P < 0.001). The extent of vascular trunk dragging was associated with axial elongation (P < 0.001) and increased border length with marginal significance (P = 0.053), but the extent of dragging could not be explained fully by their combination. The major directionality of dragging was mostly to the nasal side of the optic disc, with large variations among participants. Conclusions During axial elongation, the retinal vasculature at the posterior pole was unchanged, whereas the position of the central vascular trunk was dragged nasally. Because the central retinal vascular trunk is embedded in the LC, its dragging indicates nasal shifting of the LC, which could explain the vulnerability of myopic eyes to glaucomatous optic neuropathy.
Comparison of the Rotational Stability of Two Toric Intraocular Lenses in 1273 Consecutive Eyes Ophthalmology (IF 8.204) Pub Date : 2018-03-12 Bryan S. Lee, David F. Chang
Purpose To compare the rotational stability of the 2 most commonly used toric intraocular lenses (TIOLs). Design Retrospective cohort study in a single private practice. Subjects The study included all patients receiving an Acrysof (n = 626) or Tecnis TIOL (n = 647) over an 18-month period from April 2015 to September 2016. Patients were only excluded if their surgery could not be performed using a digital marking system. Methods All patients had cataract surgery performed in the same surgical center with a similar technique. A digital marking system with limbal vessel registration was used to record the axis of the TIOL at the conclusion of surgery. A dilated examination was performed either later on the day of surgery or the next morning, and the postoperative rotation of the 2 TIOL models was compared. Patients who required a return to the operating room for TIOL repositioning were examined to determine risk factors for reoperation and subsequent outcomes. Main Outcome Measures The primary outcome measure was the percentage of eyes with TIOL rotation >5 and >10 degrees. The second main outcome was likelihood of requiring return to the operating room to reposition a rotated TIOL. Results The Acrysof TIOL was less likely to rotate postoperatively, with 91.9% of eyes rotated ≤5 degrees at the first postoperative check compared with 81.8% of Tecnis TIOL eyes (P < 0.0001). This difference persisted for rotation ≤10 degrees (97.8% Acrysof vs. 93.2% Tecnis, P = 0.0002) and ≤15 degrees (98.6% Acrysof vs. 96.4% Tecnis, P = 0.02). The mean rotation was 2.72 degrees (95% confidence interval 2.35–3.08 degrees) for Acrysof and 3.79 degrees (95% confidence interval 3.36–4.22 degrees) for Tecnis TIOLs (P < 0.05). The Tecnis TIOL showed a strong predisposition to rotate counterclockwise, unlike the Acrysof. More Tecnis TIOL patients required repositioning (3.1% vs. 1.6%), but this did not reach statistical significance (P = 0.10). Refractive outcomes were similar between the 2 groups. Conclusions The Acrysof TIOL showed significantly greater rotational stability than the Tecnis TIOL.
Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema Ophthalmology (IF 8.204) Pub Date : 2018-03-07
Purpose To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. Design Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. Participants Participants with available plasma samples (N = 436). Methods Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. Main Outcome Measures Changes in the natural log (ln) of plasma VEGF levels. Results Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar. Conclusions These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.
Visual and Refractive Outcomes in Manual versus Femtosecond Laser–Assisted Cataract Surgery : A Single-Center Retrospective Cohort Analysis of 1838 Eyes Ophthalmology (IF 8.204) Pub Date : 2018-03-06 Thomas A. Berk, Matthew B. Schlenker, Xavier Campos-Möller, Austin M. Pereira, Iqbal Ike K. Ahmed
Purpose Femtosecond laser–assisted cataract surgery (FLACS) has emerged as an alternative to manual cataract surgery (MCS) for corneal incision and capsulorhexis creation, as well as nuclear fragmentation. This study compares postoperative refractive and visual outcomes in eyes receiving MCS or FLACS. Design Single-center, comparative, retrospective cohort analysis. Participants Consecutive eyes receiving FLACS and MCS from July 1, 2012, to July 31, 2015, at a single tertiary care center. Methods Demographic data, ocular history, preoperative measurements and biometry, and postoperative surgical results were retrospectively obtained and statistically analyzed using a generalized linear mixed model adjusting for differences in baseline characteristics and within-patient correlation. A 2-tailed P value <0.05 was considered statistically significant throughout the study. Main Outcome Measures Percentage of eyes achieving absolute error (AE) ≤0.5 diopters (D). Secondary outcomes included percentage of eyes with AE ≤0.25 D and ≤1.0 D, and percentage of distance-targeted eyes achieving uncorrected distance visual acuity (UDVA) of 20/20 or better, 20/25 or better, and 20/30 or better. Results A total of 883 eyes received MCS and 955 received FLACS among 1089 patients. Some 82.6% of FLACS eyes and 78.8% of MCS eyes had ≤0.5 D of AE at 3 weeks, representing an adjusted odds ratio (OR) of 1.28 (95% confidence interval [CI], 0.98–1.66) of FLACS relative to MCS being within target. Some 97.1% of FLACS and 97.2% of MCS eyes had ≤1.0 D of AE (OR, 0.96; 95% CI, 0.57–1.60) and 49.3% of FLACS and 46.3% of MCS eyes, ≤0.25 D of AE (OR, 1.13; 95% CI, 0.91–1.39). Factors predictive of a favorable refractive outcome included axial length between 22 and 24.8 mm, receiving a toric intraocular lens, less preoperative cylinder, and greater preoperative average keratometry. There was no significant difference in the percentage of patients targeted for distance who achieved UDVA of 20/20 or better (P = 0.30), 20/25 or better (P = 0.06), or 20/30 or better (P = 0.66) vision. Conclusions Postoperatively, there was no statistically significant difference found between eyes undergoing FLACS and eyes undergoing MCS with respect to refractive and visual outcomes.
Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs Ophthalmology (IF 8.204) Pub Date : 2018-03-02 Zhixi Li, Yifan He, Stuart Keel, Wei Meng, Robert T. Chang, Mingguang He
Purpose To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs. Design A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs. Participants We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm. Methods This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm. Main Outcome Measures The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON. Results In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%). Conclusions A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results.
Laser Peripheral Iridotomy in Primary Angle Closure : A Report by the American Academy of Ophthalmology Ophthalmology (IF 8.204) Pub Date : 2018-03-02 Sunita Radhakrishnan, Philip P. Chen, Anna K. Junk, Kouros Nouri-Mahdavi, Teresa C. Chen
Purpose To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). Methods Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. Results Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2% to 57% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0%-8% of PAC suspect (PACS), 42% to 67% of PAC, 21% to 47% of acute PAC (APAC), and 83%-100% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0% to 0.3% per year in PACS and 0% to 4% per year in PAC. Complications after LPI included IOP spike (8–17 mmHg increase from baseline in 6%–10%), dysphotopsia (2%–11%), anterior chamber bleeding (30%–41%), and cataract progression (23%–39%). Conclusions Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.
Choroidal Microvasculature Dropout Is Associated with Progressive Retinal Nerve Fiber Layer Thinning in Glaucoma with Disc Hemorrhage Ophthalmology (IF 8.204) Pub Date : 2018-03-02 Hae-Young Lopilly Park, Jin Woo Kim, Chan Kee Park
Objective We used OCT angiography (OCT-A) to investigate parapapillary choroidal microvasculature dropout (MvD) in glaucomatous eyes with or without disc hemorrhage (DH), and the association with changes in retinal nerve fiber layer (RNFL) thickness. Design An observational case-control study. Participants Eighty-two open-angle glaucoma (OAG) eyes with DH and 68 OAG eyes without DH that underwent at least 4 serial OCT examinations were included. Methods MvD was defined as complete loss of microvasculature within the choroidal layer of the parapapillary region, as revealed by standardized assessment of OCTA-derived density maps of the vessels of the optic nerve head. The circumferential extent of MvD was measured on OCT-A images. The RNFL thinning rate was calculated using a linear mixed model. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between groups stratified by DH and MvD. Main Outcome Measures MvD detection rate, the extent of MvD as measured by the MvD angle, and RNFL thinning rate. Results MvD was found in 38 (46.3%) eyes with DH at the prior DH site, which was found in only 20 (29.4%) eyes without DH, which was significantly different between the 2 groups (P = 0.025). Patients with progressive glaucoma exhibited significantly more MvD than the stable patients in both DH and no-DH groups. There were statistically significant differences between groups subdivided by the presence of DH and MvD as assessed by Kaplan-Meier analysis (log-rank test, P < 0.001). The angle of MvD was significantly greater in eyes with recurrent DH compared with eyes with single DH. Presence of DH, recurrent DH, and presence of MvD were factors associated with progressive RNFL thinning. Conclusions We found that MvD was frequent in progressive OAG eyes on the choroidal map of OCT-A, which was more frequently found at the prior DH locations in eyes with DH. This means that observing the presence of MvD using OCT-A may provide a biomarker for glaucoma progression, especially in eyes with DH.
The DISCOVER Study 3-Year Results : Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery Ophthalmology (IF 8.204) Pub Date : 2018-03-02 Justis P. Ehlers, Yasha S. Modi, Paula E. Pecen, Jeff Goshe, William J. Dupps, Aleksandra Rachitskaya, Sumit Sharma, Alex Yuan, Rishi Singh, Peter K. Kaiser, Jamie L. Reese, Carmen Calabrise, Allison Watts, Sunil K. Srivastava
Purpose To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. Design Prospective, consecutive case series. Participants Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. Methods The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. Main Outcome Measures Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. Results Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%–98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%–49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%–33.0%). Conclusions The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.
Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy : A Growth Curve Model Ophthalmology (IF 8.204) Pub Date : 2018-03-02 Mamunur Rashid, Jorma Heikkonen, Arun D. Singh, Tero T. Kivelä
Purpose To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns. Design Modeling of longitudinal observational data. Participants Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center. Methods Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor–node–metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates. Main Outcome Measures Covariates that independently predict tumor regression. Results Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression (P < 0.0001). In addition, use of ruthenium isotope as opposed to iodine isotope (P = 0.018) independently contributed to faster regression of tumor thickness. For both isotopes considered alone, initial tumor thickness was the sole clinical predictor of regression (P < 0.0001). Conclusions Regression of choroidal melanoma after brachytherapy was associated with several clinical tumor and treatment parameters, most of which were shown to reflect initial tumor size. An independent predictor of regression of tumor thickness was the isotope used. These 2 covariates need to be adjusted for when exploring the associations with the rate of regression of histopathologic or genetic features of the tumor. Our model allows such future analyses efficiently without matching.
Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration Ophthalmology (IF 8.204) Pub Date : 2018-02-21 SriniVas R. Sadda, Lisa L. Tuomi, Beiying Ding, Anne E. Fung, J. Jill Hopkins
Purpose To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD). Design Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment–controlled clinical trial. Participants Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN). Methods Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter ≥250 μm, corresponding to flat areas of well-demarcated staining on FA, excluding atrophy associated with retinal pigment epithelium tears. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included. Main Outcome Measures Macular atrophy incidence, best-corrected visual acuity (BCVA). Results At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1–9.3]; +9.1 [8.0–10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3–63.7] and 64.7 [63.2–66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76–3.42]) and fellow eye atrophy (HR, 2.02 [1.42–2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33–0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99–1.68]), but was not statistically significant. Conclusions New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24 months. Baseline subretinal fluid absence, intraretinal cyst presence, and fellow eye atrophy presence were associated with month 24 MA presence. With existing data, the benefits of ranibizumab for neovascular AMD outweighed the risk of MA development over 24 months in HARBOR, although outcomes >2 years were not evaluated.
Characterizing Anterior Segment OCT Angle Landmarks of the Trabecular Meshwork Complex Ophthalmology (IF 8.204) Pub Date : 2018-02-21 Eric L. Crowell, Laura Baker, Alice Z. Chuang, Robert M. Feldman, Nicholas P. Bell, Patricia Chévez-Barrios, Lauren S. Blieden
Purpose To identify the presence or absence of 3 identifiable landmarks: trabecular meshwork (TM), Schlemm's canal (SC), and a novel landmark termed the band of extracanalicular limbal lamina (BELL), which is a landmark adjacent to SC visible on anterior segment (AS) OCT. These landmarks also were analyzed pathologically to identify all 3 landmarks. Design Retrospective review. Participants One eye per participant from prior institutional review board-approved studies in which AS OCT imaging was performed. Methods Horizontal images from 2-dimensional angle analysis scans using a CASIA SS-1000 (Tomey, Nagoya, Japan) AS OCT were evaluated by masked readers. Logistic regression was used to analyze the potential factors of age, gender, race, intraocular pressure, gonioscopy grade, angle location, and history or presence of surgery on the visibility of these structures. Pathologic correlation on 5 previously enucleated eyes also was performed. Main Outcome Measures Presence or absence of angle landmarks—TM, SC, and BELL—using Anterior Chamber Analysis and Interpretation software (ACAI, Houston, TX). Results Three hundred three angles of 153 horizontal images were included in this study. The mean age was 51.5±16.0 years, with 98 women (64%) and 100 white persons (66%). The outer border of the BELL was observed in 288 angles (95%), TM was found in 220 angles (73%), and SC was seen in 120 angles (40%). The outer border of the BELL was more visible in white persons (P = 0.02) than Asians and in eyes with a Spaeth gonioscopy grade of E than those with a grade of A (P = 0.02). Both TM (P = 0.001) and SC (P = 0.001) were more visible in temporal angles (81% for TM, 49% for SC) than in nasal angles (64% for TM, 30% for SC). Additionally, SC was more visible in open angles (43%) than in narrow angles (27%; P = 0.02). These 3 structures were verified in a pathologic study. Conclusions We identified a novel AS OCT landmark adjacent to SC. This structure also was identified on pathologic samples from enucleated eyes. Further study is needed to determine the pathophysiologic relevance of these findings.
Treatment Outcomes in the Primary Tube Versus Trabeculectomy Study after 1 Year of Follow-up Ophthalmology (IF 8.204) Pub Date : 2018-02-21
Purpose To report 1-year treatment outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. Design Multicenter, randomized clinical trial. Participants Two hundred forty-two eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 in the tube group and 117 in the trabeculectomy group. Methods Patients were enrolled at 16 clinical centers and assigned randomly to treatment with a tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC; 0.4 mg/ml for 2 minutes). Main Outcome Measures Intraocular pressure (IOP), glaucoma medical therapy, visual acuity, visual fields, surgical complications, and failure (IOP of more than 21 mmHg or reduced by less than 20% from baseline, IOP of 5 mmHg or less, reoperation for glaucoma, or loss of light perception vision). Results The cumulative probability of failure during the first year of follow-up was 17.3% in the tube group and 7.9% in the trabeculectomy group (P = 0.01; hazard ratio, 2.59; 95% confidence interval, 1.20–5.60). Mean ± standard deviation IOP was 13.8±4.1 mmHg in the tube group and 12.4±4.4 mmHg in the trabeculectomy group at 1 year (P = 0.01), and the number of glaucoma medications was 2.1±1.4 in the tube group and 0.9±1.4 in the trabeculectomy group (P < 0.001). Postoperative complications developed in 36 patients (29%) in the tube group and 48 patients (41%) in the trabeculectomy group (P = 0.06). Serious complications requiring reoperation or producing a loss of 2 Snellen lines or more occurred in 1 patient (1%) in the tube group and 8 patients (7%) in the trabeculectomy group (P = 0.03). Conclusions Trabeculectomy with MMC had a higher surgical success rate than tube shunt implantation after 1 year in the PTVT Study. Lower IOP with use of fewer glaucoma medications was achieved after trabeculectomy with MMC compared with tube shunt surgery during the first year of follow-up. The frequency of serious complications producing vision loss or requiring reoperation was lower after tube shunt surgery relative to trabeculectomy with MMC.
Vision-Related Quality of Life Associated with Unilateral and Bilateral Ocular Conditions Ophthalmology (IF 8.204) Pub Date : 2018-02-21
Purpose To present ophthalmic patient time-tradeoff vision utilities for quantifying vision-related quality-of-life when the fellow eye still has good vision. These utilities are important for performing reliable cost-utility analyses. Design Consecutive time-tradeoff vision utilities were obtained from ophthalmic patients with good vision (20/20–20/25) in one eye and vision ranging from 20/20 to no light perception in the fellow eye over a 15-year period from 2000 through 2014. Participants Five hundred eighty-six ophthalmic participant interviews from Wills Eye Hospital, New York Eye and Ear Hospital, and ophthalmology office practices in Pennsylvania and New Jersey. Methods Participants underwent a full ophthalmic examination, after which time-tradeoff vision utilities were obtained by personal interview by the authors using a standardized, validated instrument. Main Outcome Measures Time-tradeoff vision utilities. Results Mean time-tradeoff vision utilities were as follows in participants with good vision (20/20–20/25) in at least one eye and the following visions in the fellow eyes: no light perception, 0.79; counting fingers to light perception, 0.87; 20/200 to 20/400, 0.88; 20/60 to 20/100, 0.88; 20/30 to 20/50, 0.87; and 20/20 to 20/25, 0.94. Conclusions In people with good vision (20/20–20/25) in one eye, the associated mean time-tradeoff vision utility is a remarkably consistent 0.87 to 0.88 when vision in the fellow eye ranges from 20/30 to light perception. Vision of 20/20 to 20/25 in the fellow eye results in a significantly higher associated utility of 0.94 (P < 0.01), whereas vision of no light perception in the fellow eye results in a significantly lower utility of 0.079 (P < 0.01). These utilities are important for calculating reliable patient value (quality-adjusted life-year) gains in ophthalmic cost-utility analysis populations in which there is unilateral and bilateral disease involvement.
Endophthalmitis after Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors : Management and Visual Outcomes Ophthalmology (IF 8.204) Pub Date : 2018-02-21 Kunyong Xu, Eric K. Chin, Steven R. Bennett, David F. Williams, Edwin H. Ryan, Sundeep Dev, Robert A. Mittra, Polly A. Quiram, John B. Davies, D. Wilkin Parke III, Jill B. Johnson, Herbert L. Cantrill, David R.P. Almeida
Purpose We describe the presentation of patients developing endophthalmitis after intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors. Moreover, we evaluate the management by comparing the outcomes of immediate tap and injection of intravitreal antibiotics (TAI) versus initial surgical pars plana vitrectomy (PPV). Finally, we analyze the predictive factors of visual outcomes at 6-month follow-up. Design Retrospective, single-center, nonrandomized interventional study. Participants Patients developing endophthalmitis after receiving an intravitreal injection of anti-VEGF agent between 2006 and 2016. Methods All patients received a vitreous biopsy sent for cultures before the initiation of treatment: TAI group versus PPV with intravitreal antibiotics (PPV group). Main Outcome Measures Best-corrected visual acuity (BCVA) at 6-month follow-up after treatment for endophthalmitis. Results A total of 258 357 intravitreal injections occurred over the course of the 10-year period, of which 40 patients (0.016%) had endophthalmitis within 3 weeks after injection. In total, 34 patients (85.0%) had pain and 25 patients (62.5%) had hypopyon on initial examination. Among 24 culture-positive cases, 66.7% of the causative organisms were coagulase-negative Staphylococcus, followed by Streptococcus species (10.0%). The best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]) at 6-month follow-up was significantly worse for patients who had a positive culture for Streptococcus species (4.0; standard deviation [SD], 0.8) (approximately light perception) compared with those who had a positive culture for coagulase-negative Staphylococcus (0.4; SD, 0.3) (∼20/50) (P < 0.0001). Compared with the TAI group, a higher proportion of samples were culture-positive in the PPV group (90.9% vs. 48.3%, P = 0.03). There was no statistically significant difference in BCVA at 6-month follow-up between the TAI and PPV groups. Younger age (<85 years) and lower intraocular pressure (IOP) at presentation were predictive of achieving a BCVA of 20/400 or better at 6-month follow-up after treatment. Initial management (TAI vs. PPV), duration of symptoms, presence of pain, presence of hypopyon, presenting BCVA, and culture status (positive vs. negative) were not found to be predictive of visual outcomes at 6-month follow-up. Conclusions No significant difference in BCVA at 6-month follow-up was detected between the TAI and PPV groups. Younger age and lower IOP at presentation were associated with better visual outcomes at 6-month follow-up.
Interocular Axial Length and Corneal Power Differences as Predictors of Postoperative Refractive Outcomes after Cataract Surgery Ophthalmology (IF 8.204) Pub Date : 2018-02-16 Vinay Kansal, Matthew Schlenker, Iqbal Ike K. Ahmed
Purpose To determine whether differences between eyes in axial length (AL) and corneal power (K) on optical biometry are predictive of refractive outcomes. Design Retrospective cohort study. Participants A total of 729 patients (1458 eyes) who underwent bilateral phacoemulsification at TLC (Mississauga, Ontario, Canada) from September 2013 to August 2015. Methods We compared the proportion of patients having >0.5 diopters (D) of refractive error from target stratified by interocular axial length differences (IALDs) and interocular K differences (IKDs) between eyes as measured by optical biometry (IOL-Master, Carl Zeiss Meditec, Oberkochen, Germany). Analysis was repeated for 0.25 D or 1.0 D targets and for patients with uncorrected visual acuity (UCVA) >0.3 logarithm of the minimum angle of resolution (logMAR) postoperatively. Main Outcome Measures Proportions, odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were computed using generalized estimating equations to account for within-patient correlation. Results Some 79.1% of eyes were ≤0.5 D of refractive target, 47.0% were ≤0.25 D, and 97.2% were ≤1.0 D. The OR of having a refractive outcome >0.5 D from target for IALD cutoff of 0.2 mm was 1.4 (1.1–1.8), of 0.3 mm was 1.6 (1.2–2.1), and of 0.4 mm was 1.8 (1.3–2.5). This translates to 70.0% (63.5–75.7) within target for IALD of ≥0.4 mm versus 80.7% (78.4–82.9) for <0.4 mm. For a given patient with IALD, the chance of being off target was similar for the shorter and longer eye. Eyes outside of target were twice as likely to be <−0.5 D than >0.5 D. Interocular K difference was largely not associated with prediction error, yet larger IKD-flat, steep, and average were associated with increased odds of UCVA >0.3 logMAR postoperatively. Conclusions Interocular axial length difference of as little as ≥0.2 mm is associated with a higher chance of >0.5 D of refractive error from target and worse UCVA. Interocular K difference was not associated with worse refractive error from target, although a difference of ≥0.4 D was associated with worse UCVA. These cutoffs should be considered in preoperative planning and discussion with patients. Future study is required to assess whether repeating measurements, using adjunctive measurement devices, or attempting to separate true differences from artifact based on preoperative refractive characteristics reduces residual refractive error.
Dexamethasone Inserts in Noninfectious Uveitis : A Single-Center Experience Ophthalmology (IF 8.204) Pub Date : 2018-02-16 Dominika Pohlmann, Gerrit A. vom Brocke, Sibylle Winterhalter, Theresa Steurer, Sabrina Thees, Uwe Pleyer
Purpose To report the effectiveness of repeated intravitreal dexamethasone (DEX) inserts in noninfectious uveitis patients. Design Prospective, single-center, interventional clinical trial between February 2010 and March 2015. Participants Patients with noninfectious uveitis with cystoid macular edema and/or vitreitis. Methods Patients were treated with a 700-μg intravitreal DEX insert (Ozurdex; Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months after injection. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events were recorded. Main Outcome Measures Primary outcome was the reduction of CRT. Secondary outcome was the improvement in BCVA and reduction of VH. Results In total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were women (68%). The mean age of all participants was 57 years (range, 24–88 years). More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections were 1.54±0.5 (standard deviation [SD]), 1.98±0.84, and 2.46±1.1 over 12, 18, and 24 months, respectively. Central retinal thickness decreased significantly (P < 0.001) from 465 μm at baseline to 318, 342, and 388 μm after 1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a second, third, and fourth DEX insert. Patients with idiopathic uveitis and sarcoidosis benefited well from DEX inserts. The greatest overall benefit was achieved in patients with no systemic treatment and patients receiving antimetabolites and cyclosporin A. A significant VH score reduction was documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6 months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and after 3 months (P = 0.001) was seen. Conclusions The repeated longer-term administration of DEX inserts in noninfectious uveitis patients, either alone or in combination with other therapies, led to improved CRT, BCVA, and VH. Underlying diseases and concomitant systemic therapy seem to have an impact on overall treatment benefit. Ocular complications were reversible and were managed by local treatment, with exception of cataract formation.
Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the Severity of Dry Eye Ophthalmology (IF 8.204) Pub Date : 2018-02-16 Chi Hoang Viet Vu, Motoko Kawashima, Masakazu Yamada, Kazuhisa Suwaki, Miki Uchino, Chika Shigeyasu, Yoshimune Hiratsuka, Norihiko Yokoi, Kazuo Tsubota
Purpose To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED). Design Cross-sectional observational study. Participants This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21–90 years]) for analysis. Methods Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated. Main Outcome Measures Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score. Results We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001). Conclusions This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype.
Return to the Operating Room after Macular Surgery : IRIS Registry Analysis Ophthalmology (IF 8.204) Pub Date : 2018-02-14 D. Wilkin Parke III, Flora Lum
Purpose To investigate the rate of return to the operating room after vitrectomy surgery to treat macular hole or epiretinal membrane. Design A retrospective registry cohort. Participants Individuals receiving care in ophthalmology practices participating in the Academy IRIS (Intelligent Research in Sight) Registry. Methods Data from the IRIS Registry were analyzed for patients who underwent vitrectomy for macular holes or epiretinal membranes. Cases were identified by the combination of International Classification of Diseases, 9th revision code (362.54, 362.56) and a current procedural terminology (CPT) code for vitrectomy surgery between January 1, 2013 and June 30, 2017. Main Outcome Measures The eyes that underwent additional eye surgery within 1 year after initial vitrectomy for macular hole or epiretinal membrane were identified, as was the nature of the additional procedures per CPT code. Results A total of 41 475 eyes underwent vitrectomy for macular hole and 73 219 eyes underwent vitrectomy for epiretinal membrane during the study period. In the macular hole group, 7573 had a second surgery within 1 year, and 2827 (6.8%) had a second surgery that was not cataract related. In the epiretinal membrane group, 12 433 had a second surgery within 1 year, 4022 (5.5%) of which were not cataract related. In the macular hole group, 4.6% of eyes returned to the operating room for another macular hole repair surgery, and 2.0% returned for retinal detachment repair. In the epiretinal membrane group, 1.4% returned for a second vitrectomy with membrane stripping, and 2.5% returned for retinal detachment repair. Conclusions This registry-based study encompassed a large number of patients but was limited by the inaccessibility of some information and the potential for inaccurate medical records or coding, as it obtained data from multiple electronic health records entities. Excluding cataract surgery, approximately 6% of eyes that underwent vitrectomy to address macular hole or epiretinal membrane returned for a second ophthalmic procedure within a year. In the macular hole group, most secondary non-cataract surgeries were for another macular hole repair procedure. For both macular holes and epiretinal membranes, approximately 2% of eyes required retinal detachment repair surgery within 1 year.
Predicting Visual Acuity by Using Machine Learning in Patients Treated for Neovascular Age-Related Macular Degeneration Ophthalmology (IF 8.204) Pub Date : 2018-02-14 Markus Rohm, Volker Tresp, Michael Müller, Christoph Kern, Ilja Manakov, Maximilian Weiss, Dawn A. Sim, Siegfried Priglinger, Pearse A. Keane, Karsten Kortuem
Purpose To predict, by using machine learning, visual acuity (VA) at 3 and 12 months in patients with neovascular age-related macular degeneration (AMD) after initial upload of 3 anti–vascular endothelial growth factor (VEGF) injections. Design Database study. Participants For the 3-month VA forecast, 653 patients (379 female) with 738 eyes and an average age of 74.1 years were included. The baseline VA before the first injection was 0.54 logarithm of the minimum angle of resolution (logMAR) (±0.39). A total of 456 of these patients (270 female, 508 eyes, average age: 74.2 years) had sufficient follow-up data to be included for a 12-month VA prediction. The baseline VA before the first injection was 0.56 logMAR (±0.42). Methods Five different machine-learning algorithms (AdaBoost.R2, Gradient Boosting, Random Forests, Extremely Randomized Trees, and Lasso) were used to predict VA in patients with neovascular AMD after treatment with 3 anti-VEGF injections. Clinical data features came from a data warehouse (DW) containing electronic medical records (41 features, e.g., VA) and measurement features from OCT (124 features, e.g., central retinal thickness). The VA of patient eyes excluded from machine learning was predicted and compared with the ground truth, namely, the actual VA of these patients as recorded in the DW. Main Outcome Measures Difference in logMAR VA after 3 and 12 months upload phase between prediction and ground truth as defined. Results For the 3-month VA forecast, the difference between the prediction and ground truth was between 0.11 logMAR (5.5 letters) mean absolute error (MAE)/0.14 logMAR (7 letters) root mean square error (RMSE) and 0.18 logMAR (9 letters) MAE/0.2 logMAR (10 letters) RMSE. For the 12-month VA forecast, the difference between the prediction and ground truth was between 0.16 logMAR (8 letters) MAE/0.2 logMAR (10 letters) RMSE and 0.22 logMAR (11 letters) MAE/0.26 logMAR (13 letters) RMSE. The best performing algorithm was the Lasso protocol. Conclusions Machine learning allowed VA to be predicted for 3 months with a comparable result to VA measurement reliability. For a forecast after 12 months of therapy, VA prediction may help to encourage patients adhering to intravitreal therapy.
Development and Course of Scars in the Comparison of Age-related Macular Degeneration Treatments Trials Ophthalmology (IF 8.204) Pub Date : 2018-02-14 Ebenezer Daniel, Wei Pan, Gui-shuang Ying, Benjamin J. Kim, Juan E. Grunwald, Frederick L. Ferris III, Glenn J. Jaffe, Cynthia A. Toth, Daniel F. Martin, Stuart L. Fine, Maureen G. Maguire
Purpose To describe risk factors for scar formation and changes to fibrotic scar through 5 years in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Multicenter, prospective cohort study. Participants A total of 1061 subjects in CATT. Methods Color photographic and fluorescein angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence of scar formation was estimated with Kaplan–Meier curves. Risk factors were assessed with Cox regression models. Main Outcome Measures Scar formation, fibrotic scar area, and macular atrophy associated with fibrotic scar (“atrophy”). Results Cumulative proportion of eyes with scar was 32%, 46%, and 56% at years 1, 2, and 5, respectively. Baseline factors associated with increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI]) were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34–6.04) versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49–3.47) versus no hemorrhage, retinal thickness >212 μm (aHR, 2.58; 95% CI, 1.69–3.94) versus <120 μm, subretinal tissue complex thickness >275 μm (aHR, 2.64; 95% CI, 1.81–3.84) versus ≤75 μm, subretinal fluid thickness >25 μm (aHR, 1.31; 95% CI, 0.97–1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72; 95% CI, 1.25–2.36) versus 20/50 or worse, retinal pigment epithelium elevation absence (aHR, 1.71; 95% CI, 1.21–2.41), and subretinal hyperreflective material (aHR, 1.72; 95% CI, 1.25–2.36). Among 68 eyes that developed fibrotic scar at year 1, VA decreased by a mean of additional 13 letters between years 1 and 5. Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively. Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5, respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation between scar growth and atrophy growth. The rate of growth for both was similar between the clinical trial and observation periods. Conclusions Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.
Dexamethasone Intracameral Drug-Delivery Suspension for Inflammation Associated with Cataract Surgery : A Randomized, Placebo-Controlled, Phase III Trial Ophthalmology (IF 8.204) Pub Date : 2018-02-13 Eric Donnenfeld, Edward Holland
Purpose To evaluate the safety and efficacy of an anterior chamber intracameral dexamethasone drug-delivery suspension (IBI-10090; DEXYCU; Icon Bioscience Inc., Newark, CA) that provides medication for up to 21 days with a single application in treating postoperative inflammation in patients undergoing cataract surgery. Design Prospective, randomized, double-masked, multicenter trial. Participants Patients with preoperative best-corrected visual acuity of 20/30 to 20/200 undergoing unilateral cataract surgery by phacoemulsification were randomized to receive IBI-10090 or placebo. Methods Three hundred ninety-four patients were randomized 1:2:2 to receive 5-μl injections of placebo or 5-μl injections of 342 or 517 μg IBI-10090 dexamethasone drug delivery suspension injected into the anterior chamber at the conclusion of cataract surgery. Patients were followed for 90 days after surgery. Main Outcome Measures Primary outcome was anterior chamber cell (ACC) clearing (ACC score of 0) in the study eye at postoperative day (POD) 8. Secondary outcome measures were anterior chamber flare and ACC plus flare clearing in the study eye. Ocular and nonocular adverse events were assessed. Results Anterior chamber cell clearing at POD 8 was achieved in 25.0% of eyes in the placebo group and in 63.1% and 66.0% of eyes in the 342- and 517-μg treatment groups, respectively (P < 0.001). Anterior chamber flare clearing at POD 8 was achieved by 63.8% of eyes in the placebo group and in 92.4% and 89.1% of eyes in the 342- and 517-μg IBI-10090 treatment groups, respectively (P < 0.001). Anterior chamber cell plus flare clearing at POD 8 was achieved in 33.8% of eyes receiving placebo and in 63.1% and 67.3% of eyes receiving 342- and 517-μg IBI-10090, respectively (P < 0.001). Adverse events among the 3 groups were similar, and no serious ocular adverse events were reported up to POD 90. Conclusions The IBI-10090 dexamethasone drug-delivery suspension placed in the anterior chamber after cataract surgery at concentrations of 342 and 517 μg was safe and effective in treating inflammation occurring after cataract surgery and may be an alternative to corticosteroid drop installation in this patient population.
Consistent Long-Term Therapy of Neovascular Age-Related Macular Degeneration Managed by 50 or More Anti–VEGF Injections Using a Treat-Extend-Stop Protocol Ophthalmology (IF 8.204) Pub Date : 2018-02-10 Sean D. Adrean, Siyang Chaili, Hema Ramkumar, Ash Pirouz, Scott Grant
Purpose To examine the clinical results for patients with neovascular age-related macular degeneration (nAMD) who were managed with a treat-extend-stop (TES) protocol and received 50 or more injections of anti–vascular endothelial growth factor (VEGF) agents. Design Retrospective case study. Participants Data for patients from a private retina practice meeting the following criteria were included: diagnosis of nAMD and having received 50 or more intravitreal injections of anti-VEGF agents. Methods The patients' baseline visual acuity (VA; obtained using Snellen charts and converted to Early Treatment Diabetic Retinopathy Study [ETDRS] letters), age, length of follow-up, anti-VEGF agents used, and interval between treatments were obtained. These data were examined through the 51st injection and at the last follow-up examination. Patients were excluded if they lost significant vision because of a diagnosis unrelated to AMD during therapy. Main Outcome Measures Visual acuity and complications. Results Sixty-seven eyes of 71 patients were identified who met inclusion criteria. The mean age of patients was 83.0 years. Women made up 58.2% of the study population, whereas men constituted 41.8%. The mean initial VA was 55.6 ETDRS letters. The mean duration of follow-up at the 51st visit for an injection was 6.4 years, and the mean duration of follow-up at the last visit was 8 years. The mean number of injections at final follow-up was 63.7. The mean interval between treatments at the 51st follow-up was 5.4 weeks, and the mean follow-up at the last examination was 6.4 weeks. Mean VA at the 51st injection was 65.3 letters, and the mean change from baseline was 9.7 letters (P < 0.001, Student paired t test). The mean vision gained at last follow-up was 8.7 letters from baseline (P < 0.001), or 64.3 letters. Conclusions In this study, patients gained a mean of 2 ETDRS lines after 50 injections. This study had a mean follow-up of 8 years, and 35.2% of eyes had a 3-line or more gain in VA at the last follow-up examination. Patients who require consistent long-term anti-VEGF therapy, managed with a TES protocol, are likely able to maintain or improve their vision.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
- Acc. Chem. Res.
- ACS Appl. Mater. Interfaces
- ACS Biomater. Sci. Eng.
- ACS Catal.
- ACS Cent. Sci.
- ACS Chem. Biol.
- ACS Chem. Neurosci.
- ACS Comb. Sci.
- ACS Earth Space Chem.
- ACS Energy Lett.
- ACS Infect. Dis.
- ACS Macro Lett.
- ACS Med. Chem. Lett.
- ACS Nano
- ACS Omega
- ACS Photonics
- ACS Sens.
- ACS Sustainable Chem. Eng.
- ACS Synth. Biol.
- Acta Biomater.
- Acta Crystallogr. A Found. Adv.
- Acta Mater.
- Adv. Colloid Interface Sci.
- Adv. Electron. Mater.
- Adv. Energy Mater.
- Adv. Funct. Mater.
- Adv. Healthcare Mater.
- Adv. Mater.
- Adv. Mater. Interfaces
- Adv. Opt. Mater.
- Adv. Sci.
- Adv. Synth. Catal.
- AlChE J.
- Anal. Bioanal. Chem.
- Anal. Chem.
- Anal. Chim. Acta
- Anal. Methods
- Angew. Chem. Int. Ed.
- Annu. Rev. Anal. Chem.
- Annu. Rev. Biochem.
- Annu. Rev. Environ. Resour.
- Annu. Rev. Food Sci. Technol.
- Annu. Rev. Mater. Res.
- Annu. Rev. Phys. Chem.
- Appl. Catal. A Gen.
- Appl. Catal. B Environ.
- Appl. Clay. Sci.
- Appl. Energy
- Aquat. Toxicol.
- Arab. J. Chem.
- Asian J. Org. Chem.
- Atmos. Environ.
- Carbohydr. Polym.
- Catal. Commun.
- Catal. Rev. Sci. Eng.
- Catal. Sci. Technol.
- Catal. Today
- Cell Chem. Bio.
- Cem. Concr. Res.
- Ceram. Int.
- Chem. Asian J.
- Chem. Bio. Drug Des.
- Chem. Biol. Interact.
- Chem. Commun.
- Chem. Educ. Res. Pract.
- Chem. Eng. J.
- Chem. Eng. Sci.
- Chem. Eur. J.
- Chem. Mater.
- Chem. Phys.
- Chem. Phys. Lett.
- Chem. Phys. Lipids
- Chem. Rev.
- Chem. Sci.
- Chem. Soc. Rev.
- Chin. J. Chem.
- Combust. Flame
- Compos. Part A Appl. Sci. Manuf.
- Compos. Sci. Technol.
- Compr. Rev. Food Sci. Food Saf.
- Comput. Chem. Eng.
- Constr. Build. Mater.
- Coordin. Chem. Rev.
- Corros. Sci.
- Crit. Rev. Food Sci. Nutr.
- Crit. Rev. Solid State Mater. Sci.
- Cryst. Growth Des.
- Curr. Opin. Chem. Eng.
- Curr. Opin. Colloid Interface Sci.
- Curr. Opin. Environ. Sustain
- Curr. Opin. Solid State Mater. Sci.
- Ecotox. Environ. Safe.
- Electrochem. Commun.
- Electrochim. Acta
- Energy Environ. Sci.
- Energy Fuels
- Energy Storage Mater.
- Environ. Impact Assess. Rev.
- Environ. Int.
- Environ. Model. Softw.
- Environ. Pollut.
- Environ. Res.
- Environ. Sci. Policy
- Environ. Sci. Technol.
- Environ. Sci. Technol. Lett.
- Environ. Sci.: Nano
- Environ. Sci.: Processes Impacts
- Environ. Sci.: Water Res. Technol.
- Eur. J. Inorg. Chem.
- Eur. J. Med. Chem.
- Eur. J. Org. Chem.
- Eur. Polym. J.
- J. Acad. Nutr. Diet.
- J. Agric. Food Chem.
- J. Alloys Compd.
- J. Am. Ceram. Soc.
- J. Am. Chem. Soc.
- J. Am. Soc. Mass Spectrom.
- J. Anal. Appl. Pyrol.
- J. Anal. At. Spectrom.
- J. Antibiot.
- J. Catal.
- J. Chem. Educ.
- J. Chem. Eng. Data
- J. Chem. Inf. Model.
- J. Chem. Phys.
- J. Chem. Theory Comput.
- J. Chromatogr. A
- J. Chromatogr. B
- J. Clean. Prod.
- J. CO2 UTIL.
- J. Colloid Interface Sci.
- J. Comput. Chem.
- J. Cryst. Growth
- J. Dairy Sci.
- J. Electroanal. Chem.
- J. Electrochem. Soc.
- J. Environ. Manage.
- J. Eur. Ceram. Soc.
- J. Fluorine Chem.
- J. Food Drug Anal.
- J. Food Eng.
- J. Food Sci.
- J. Funct. Foods
- J. Hazard. Mater.
- J. Heterocycl. Chem.
- J. Hydrol.
- J. Ind. Eng. Chem.
- J. Inorg. Biochem.
- J. Magn. Magn. Mater.
- J. Mater. Chem. A
- J. Mater. Chem. B
- J. Mater. Chem. C
- J. Mater. Process. Tech.
- J. Mech. Behav. Biomed. Mater.
- J. Med. Chem.
- J. Membr. Sci.
- J. Mol. Catal. A Chem.
- J. Mol. Liq.
- J. Nat. Gas Sci. Eng.
- J. Nat. Prod.
- J. Nucl. Mater.
- J. Org. Chem.
- J. Photochem. Photobiol. C Photochem. Rev.
- J. Phys. Chem. A
- J. Phys. Chem. B
- J. Phys. Chem. C
- J. Phys. Chem. Lett.
- J. Polym. Sci. A Polym. Chem.
- J. Porphyr. Phthalocyanines
- J. Power Sources
- J. Solid State Chem.
- J. Taiwan Inst. Chem. E.
- Macromol. Rapid Commun.
- Mass Spectrom. Rev.
- Mater. Chem. Front.
- Mater. Des.
- Mater. Horiz.
- Mater. Lett.
- Mater. Sci. Eng. A
- Mater. Sci. Eng. R Rep.
- Mater. Today
- Meat Sci.
- Med. Chem. Commun.
- Microchem. J.
- Microchim. Acta
- Micropor. Mesopor. Mater.
- Mol. Biosyst.
- Mol. Cancer Ther.
- Mol. Catal.
- Mol. Nutr. Food Res.
- Mol. Pharmaceutics
- Mol. Syst. Des. Eng.
- Nano Energy
- Nano Lett.
- Nano Res.
- Nano Today
- Nano-Micro Lett.
- Nanomed. Nanotech. Biol. Med.
- Nanoscale Horiz.
- Nat. Catal.
- Nat. Chem.
- Nat. Chem. Biol.
- Nat. Commun.
- Nat. Energy
- Nat. Mater.
- Nat. Med.
- Nat. Methods
- Nat. Nanotech.
- Nat. Photon.
- Nat. Prod. Rep.
- Nat. Protoc.
- Nat. Rev. Chem.
- Nat. Rev. Drug. Disc.
- Nat. Rev. Mater.
- Natl. Sci. Rev.
- Neurochem. Int.
- New J. Chem.
- NPG Asia Mater.
- npj 2D Mater. Appl.
- npj Comput. Mater.
- npj Flex. Electron.
- npj Mater. Degrad.
- npj Sci. Food
- Pharmacol. Rev.
- Pharmacol. Therapeut.
- Photochem. Photobiol. Sci.
- Phys. Chem. Chem. Phys.
- Phys. Life Rev.
- PLOS ONE
- Polym. Chem.
- Polym. Degrad. Stabil.
- Polym. J.
- Polym. Rev.
- Powder Technol.
- Proc. Combust. Inst.
- Prog. Cryst. Growth Ch. Mater.
- Prog. Energy Combust. Sci.
- Prog. Mater. Sci.
- Prog. Photovoltaics
- Prog. Polym. Sci.
- Prog. Solid State Chem.