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  • Effect of a Schlemm’s Canal Microstent on Early Post-operative IOP Following Cataract Surgery: An Analysis of the HORIZON randomized controlled trial
    Ophthalmology (IF 7.732) Pub Date : 2020-01-23
    Nazlee Zebardast; Chengjie Zheng; Henry Jampel

    Purpose To compare early postoperative IOP in patients who underwent cataract surgery alone, with those who underwent cataract surgery combined with implantation of a Hydrus® Microstent. Design Subanalysis of data from the randomized controlled HORIZON trial, a multicenter trial including 26 US and 12 international sites. Subjects Subjects with mild or moderate primary open angle glaucoma (POAG) and visually significant cataract with mean modified diurnal IOP between 22 and 34 mmHg after washout of IOP-lowering medications. Methods 556 subjects were randomized in a 2:1 ratio to undergo cataract surgery alone (NMS), versus cataract surgery with placement of the Hydrus Microstent (HMS). All eyes were washed out of IOP lowering medications prior to surgery and remained unmedicated until surgery. No IOP lowering prophylaxis was used post-operatively. Comprehensive eye examination including measurement of intraocular pressure was conducted on post-operative day 1, week 1 and month 1. Main outcome measure Postoperative IOP>40mmHg was analyzed as the primary outcome. Incidence of IOP rise >10mmHg above baseline unmedicated IOP and mean IOP were analyzed as secondary outcomes. Results 369 eyes were randomized to the HMS group, and 187 eyes to cataract surgery alone. The HMS and NMS groups did not differ with respect to baseline demographic or ocular characteristics. On POD1, the incidence of IOP spike defined as IOP > 40 mmHg was significantly higher at 14.4% in the NMS group, compared with 1.4% in the NMS group (p<0.001). The incidence of IOP rise ≥10 mmHg relative to baseline on POD1 was also significantly higher in the NMS than in the HMS group (22.5% vs. 3.0%, p<0.001). IOP in the NMS group was significantly higher than in the HMS group (27.6 mmHg vs 17.0 mmHg, p<0.001). In multivariable logistic regression analysis, higher baseline IOP predicted higher odds of POD1 IOP spike >40 mmHg while presence of HMS was associated with a lower likelihood of post-operative IOP spike. Conclusion The addition of a Hydrus Microstent at the time of cataract surgery lowered the risk of markedly elevated IOP in the early post-operative period in glaucoma patients.

    更新日期:2020-01-23
  • Longitudinal Macular Structure-Function Relationships in Glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2020-01-22
    Vahid Mohammadzadeh; Alessandro Rabiolo; Qiang Fu; Esteban Morales; Anne L. Coleman; Simon K. Law; Joseph Caprioli; Kouros Nouri-Mahdavi

    Purpose To investigate the relationship between longitudinal changes in macular thickness measurements from optical coherence tomography (OCT) and changes in central visual field (VF) in glaucoma patients with central or advanced damage at baseline. Design Longitudinal cohort study. Subjects 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. Methods OCT superpixels and VF locations were matched correcting for retinal ganglion cell displacement. Superpixel thickness and visual field (VF) total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell-inner plexiform layer (GCIPL) and ganglion cell layer (GCL). Correlation of structural and functional (SF) rates of change were investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with p<0.05) throughout the follow-up period. Permutation analyses were used to control specificity. Main Outcomes Measure Magnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time. Results The median (IQR) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r=0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL and GCL for 3.4° eccentricity and =0.28, 0.32, 0.31 and 0.32 for FMT, GCC, GCIPL and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year timepoints (p<0.025). Permutation analyses also confirmed this finding. Conclusion Correlations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

    更新日期:2020-01-22
  • Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration
    Ophthalmology (IF 7.732) Pub Date : 2019-07-16
    David S. Liao; Federico V. Grossi; Delphine El Mehdi; Monica R. Gerber; David M. Brown; Jeffrey S. Heier; Charles C. Wykoff; Lawrence J. Singerman; Prema Abraham; Felix Grassmann; Peter Nuernberg; Bernhard H.F. Weber; Pascal Deschatelets; Robert Y. Kim; Carol Y. Chung; Ramiro M. Ribeiro; Mohamed Hamdani; Philip J. Rosenfeld; Cedric G. Francois

    Purpose Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. Design Prospective, multicenter, randomized, sham-controlled phase 2 study. Participants Two hundred forty-six patients with GA. Methods Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. Main Outcome Measures The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. Results In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9–49; P = 0.008) and 20% (95% CI, 0–40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). Conclusions Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.

    更新日期:2020-01-21
  • Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients
    Ophthalmology (IF 7.732) Pub Date : 2019-07-11
    Zelia K. Chiu; Lyndell L. Lim; Sophie L. Rogers; Anthony J. Hall

    Purpose To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls. Design Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates. Participants Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice. Methods Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups. Main Outcome Measures Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D. Results The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29–70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52–79 nmol/l; P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46–77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall’s τ test). In a subanalysis of vitamin D–deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses). Conclusions Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.

    更新日期:2020-01-21
  • Diagnostic Performance of Three-Dimensional Thickness of Endothelium/Descemet Complex in Fuchs’ Endothelial Cell Corneal Dystrophy
    Ophthalmology (IF 7.732) Pub Date : 2020-01-19
    Taher Eleiwa; Amr Elsawy; Mohamed Tolba; William Feuer; Sonia Yoo; Mohamed Abou Shousha

    Purpose To describe the diagnostic accuracy of the regional three-dimensional (3D) endothelium/Descemet’s membrane complex thickness (En/DMT) in Fuchs’ endothelial corneal dystrophy (FECD), and to determine its potential role as an objective index of disease severity. Design Observational case-control study. Participants 104 eyes of 79 subjects (64 eyes of 41 FECD patients, and 40 eyes of 38 healthy age- and gender-matched controls). Methods All participants were imaged using HD-OCT device (Envisu R2210, Bioptigen, Buffalo Grove, IL, USA). FECD was clinically classified into early (without edema) and late-stage (with edema). Automatic and manual segmentation of the corneal layers was performed using a custom-built segmental tomography algorithm to generate 3D-thickness maps of total cornea thickness (TCT) and En/DMT of the central 6 mm cornea. Regional En/DMT, regional TCT, and central to peripheral total corneal thickness ratio (CPTR) were evaluated and correlated to the clinical severity of the disease. Intraclass Correlation Coefficients (ICC), and Bland-Altman plots were used to assess the reliability of the repeated measurements in all eyes. Main Outcome Measures CPTR, average En/DMT and TCT of central, paracentral and peripheral regions. Results In FECD, there was a significant increase in En/DMT, CPTR, and TCT as compared to controls (P < 0.001). For identifying FECD, average En/DMT of paracentral and peripheral regions achieved 94% sensitivity and 100% specificity (Cutoffs, 19 μm and 20 μm, respectively), while CPTR had 94% sensitivity with a specificity of 73% (Cutoff, 0.97). For discriminating early-stage FECD from controls, average En/DMT of central zones achieved 92% sensitivity and 97% specificity (Cutoff, 18 μm), while CPTR had 90% sensitivity and 88% specificity (Cutoff, 0.97). The average En/DMT of central, paracentral and peripheral regions was highly correlated with FECD clinical stage (Spearman’s rho = 0.813, 0.793, and 0.721; all P < 0.001, respectively), compared to (0.672 and 0.481; P < 0.001) for CPTR and mean TCT of paracentral zones, respectively. ICC values ranged from 0.98 (En/DMT) to 0.99 (TCT) with a good agreement between the automatic and manual measurements. Conclusion Regional 3D-En/DMT is a novel diagnostic tool of FECD that can be used to quantify the disease severity with excellent reliability.

    更新日期:2020-01-21
  • Prevalence of Maculopathy Associated with Long Term Pentosan Polysulfate Therapy
    Ophthalmology (IF 7.732) Pub Date : 2020-01-17
    Robin A. Vora; Amar P. Patel; Ronald Melles

    A significant number of Kaiser Permanente Northern California patients who had a cumulative exposure to 500 grams or more of pentosan polysulfate sodium (PPS) developed a pigmentary maculopathy.

    更新日期:2020-01-17
  • Brolucizumab: Evolution Through Preclinical and Clinical Studies, and the Implications for the Management of nAMD
    Ophthalmology (IF 7.732) Pub Date : 2020-01-17
    Quan Dong Nguyen; Arup Das; Diana V. Do; Pravin Dugel; Andre Gomes; Frank G. Holz; Adrian Koh; Carolyn Pan; Yasir J. Sepah; Nikhil Patel; Heather MacLeod; Patrik Maurer

    Improving or maintaining visual acuity is the main goal for treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal anti-VEGF injections, which places substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomical outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as RTH258 and ESBA1008), is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of ∼26kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single intravitreal brolucizumab administration in patients with treatment-naïve nAMD was first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to BCVA and brolucizumab achieving greater fluid resolution. In addition, brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval and the outcomes provided key information for the study design and endpoints of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, following 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomical parameters (central subfield thickness [CST], intra- or sub-retinal fluid [IRF/SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6 mg-treated eyes had disease activity versus aflibercept, and anatomical outcome results at Weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6-mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until Week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular intravitreal injections for patients with nAMD.

    更新日期:2020-01-17
  • Small incision lenticule extraction for the correction of myopia with astigmatism: outcomes of the US Food and Drug administration premarket approval clinical trial
    Ophthalmology (IF 7.732) Pub Date : 2020-01-15
    Jon G. Dishler; Stephen Slade; Stefanie Seifert; Steven C. Schallhorn

    Objective To present outcomes of the US food and drug administration premarket approval clinical trial of the small incision lenticule extraction (SMILE) for the correction of myopia and astigmatism. Design Prospective multi-center clinical trial Subjects The study included 357 eyes of 357 patients treated with SMILE (50 for myopia and 307 for myopia with astigmatism). Preoperative sphere ranged between -1.00 and -10.00 D, with the manifest spherical equivalent (MSE) up to -11.50 D and the refractive cylinder up to -3.00 D. Methods Subjects were followed for 12 months. Corrected (CDVA) and uncorrected (UDVA) visual acuity, stability of the manifest refraction and vector analysis of refractive cylinder are presented for the 307 eyes treated for myopia with astigmatism. Adverse events are presented for all 357 eyes. Results Of the 307 astigmatic eyes enrolled in the study, 304 were successfully treated. In three eyes, the procedure was aborted due to intraoperative suction loss. The mean MSE reduced from -5.39 ± 2.30D at baseline to -0.01 ± 0.24D at 12 months. Of all eyes, 95.3% were within 0.50D of emmetropia at 12 months. The percentage of eyes with UDVA 20/20 or better was 89.0%. There was no loss of 2 or more lines of CDVA at the 12-month visit. The refractive cylinder reduced from -1.53 ± 0.70D at baseline to -0.18 ± 0.31D at 12 months. The mean correction ratio (CR) of refractive cylinder was 0.96 ± 0.16, but there was a slight undercorrection apparent for higher attempted corrections of astigmatism. There were 3 intraoperative adverse events associated with difficult lenticule removal and resultant cap tear and all resolved without sequelae at postoperative day 1. During the postoperative period, 8 adverse events were recorded, but none of them had significant consequences. Conclusion SMILE for the treatment of myopia and astigmatism was safe and effective and the reported adverse events had no significant impact on visual acuity. Slight undercorrection of refractive cylinder requires further attention.

    更新日期:2020-01-15
  • Ganglion Cell Complex Thickness and Macula Vessel Density Loss in Primary Open Angle Glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2020-01-13
    Huiyuan Hou; Sasan Moghimi; James A. Proudfoot; Elham Ghahari; Rafaella C. Penteado; Christopher Bowd; Diya Yang; Robert N. Weinreb

    Purpose To characterize the rate of change of ganglion cell complex(GCC) thickness and macula vessel density in healthy, pre-perimetric glaucoma and primary open angle glaucoma(POAG) eyes. Design Prospective, longitudinal study. Participants 139 eyes(23 healthy eyes, 36 pre-perimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for pre-perimetric glaucoma eyes, and 2.6 years for POAG eyes. Methods Optical coherence tomography angiography(OCT-A)-based vessel density and OCT-based structural thickness of the same 3×3 mm2 GCC scan slab were evaluated at each visit. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors, including severity of disease and intraocular pressure(IOP), were evaluated. Main Outcome Measures The rates of GCC thinning and macula vessel density loss. Results Significant rates of both whole image GCC thinning and macula vessel density decrease were detectable in all diagnostic groups(all P<0.05). In healthy eyes and pre-perimetric glaucoma eyes, the normalized rates of GCC thinning and macula vessel density decrease were comparable(all P>0.1). In contrast, the normalized rate(mean,95% CI) of macula vessel density decrease in the POAG eyes(-7.12(-8.36,-5.88)%/year) was significantly faster than GCC thinning(-2.13(-3.35,-0.90)%/year,P<0.001). In the POAG group, more than two-thirds of the eyes showed faster macula vessel density decrease than GCC thinning; faster macula vessel density decrease rate was significantly associated with worse glaucoma severity(P=0.037). The association between GCC thinning rate and glaucoma severity was not significant(P=0.586). IOP during follow-up significantly affected the rate of GCC thinning in all groups(all P<0.05), but had no association with the rate of macula vessel density decrease. Conclusions Both GCC thinning and macula vessel density decrease were detectable over time in all 3 diagnostic groups. In POAG eyes, macula vessel density decrease was faster than GCC thinning and associated with severity of disease. Macula vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

    更新日期:2020-01-13
  • Collaborative Ocular Tuberculosis Study (COTS) Consensus Guidelines on the Management of Tubercular Uveitis – Report 1: Guidelines for Initiating Anti-Tubercular Therapy in Tubercular Choroiditis
    Ophthalmology (IF 7.732) Pub Date : 2020-01-11
    Rupesh Agrawal; Ilaria Testi; Sarakshi Mahajan; Yew Sen Yuen; Aniruddha Agarwal; Onn Min Kon; Talin Barisani-Asenbauer; John H. Kempen; Amod Gupta; Douglas A. Jabs; Justine R. Smith; Quan Dong Nguyen; Carlos Pavesio; Vishali Gupta

    Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society (IOIS) and the International Uveitis Study Group (IUSG) systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of anti-tubercular therapy (ATT) in patients with tubercular uveitis. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, utilizing Oxford levels of medical evidence. In total, 162 statements were identified around when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a two-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the three subtypes of tubercular choroiditis and in addition 12 consensus statements were developed on the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of any one of the positive immunological tests along with radiological features suggestive of TB. For tubercular serpiginous-like choroiditis and tuberculoma, even one positive immunological test was considered sufficient to recommend ATT even if there are no radiological features suggestive of TB. Conclusions Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion and practical experience, to bridge the gap between clinical need and available medical evidence.

    更新日期:2020-01-13
  • Private Equity in Ophthalmology and Optometry: Analysis of Acquisitions from 2012 to 2019 in the United States
    Ophthalmology (IF 7.732) Pub Date : 2020-01-11
    Evan M. Chen; Jacob T. Cox; Tedi Begaj; Grayson W. Armstrong; Rahul N. Khurana; Ravi Parikh

    Purpose To identify temporal and geographic trends in private equity-backed acquisitions of ophthalmology and optometry practices in the United States. Design A cross-sectional study using private equity acquisition and investment data from January 1, 2012 to October 20, 2019. Participants A total of 228 private equity acquisitions of ophthalmology and optometry practices in the United States between 2012 and 2019. Methods Acquisition and financial investment data were compiled from six financial databases, four industry news outlets and publicly available press releases from private equity firms or platform companies. Main Outcome Measures Yearly trends in ophthalmology and optometry acquisitions including number of total acquisitions, clinical locations and providers of acquired practices as well as subsequent sales, median holding period, geographic footprint and financing status of each platform company. Results A total of 228 practices associated with 1,466 clinical locations and 2,146 ophthalmologists or optometrists were acquired by 29 private equity-backed platform companies. Of these acquisitions, 127, 9, and 92 were comprehensive/multispecialty, retina and optometry practices, respectively. Acquisitions increased rapidly between 2012 and 2019—42 practices were acquired between 2012 and 2016 compared to 186 from 2017 to 2019. Financing rounds of platform companies paralleled temporal acquisition trends. Three platform companies, comprising 60% of platforms formed before 2016, were subsequently sold or recapitalized to new private equity investors by the end of this study period with a median holding period of 3.5 years. In terms of geographic distribution, acquisitions occurred in 40 states with a majority of private equity firms developing multi-state platform companies. New York and California were the two states with the greatest number of PE acquisitions with 22 and 19 respectively. Conclusions Private equity-backed acquisitions of ophthalmology and optometry practices have rapidly increased since 2012, with some platform companies having already been sold or recapitalized to new investors. Private equity-backed platform companies have developed both regionally focused and multi-state models of add-on acquisitions. Future research should assess the impact of private equity investment on patient, provider and practice metrics including health outcomes, expenditures, procedural volume and staff employment.

    更新日期:2020-01-13
  • Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3, Randomized Trial
    Ophthalmology (IF 7.732) Pub Date : 2020-01-10
    Steven Yeh; Rahul N. Khurana; Milan Shah; Christopher R. Henry; Robert C. Wang; Jennifer M. Kissner; Thomas A. Ciulla; Glenn Noronha

    Purpose Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed under the rationale of providing higher drug concentrations to posterior ocular structures compared to other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected CLS-TA, a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Design The PEACHTREE study was a phase 3 masked, randomized trial. Participants 160 patients with macular edema (ME) secondary to noninfectious uveitis. Patients were required to have a best corrected visual acuity (BCVA) score of ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/800 Snellen equivalent) and ≤70 letters read (20/40) in the study eye. Methods Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham, with administrations at day 0 and week 12. Main Outcome Measures The primary endpoint was improvement from baseline of ≥15 ETDRS letters in BCVA at week 24. The secondary endpoint was reduction from baseline in central subfield thickness at week 24. Results In the CLS-TA arm, 47% of patients gained ≥15 ETDRS letters in BCVA versus 16% in the control arm (p<0.001), meeting the primary endpoint. Mean reductions in central subfield thickness from baseline were 153 μm versus 18 μm (p<0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%). Conclusions Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

    更新日期:2020-01-11
  • The Association between Medication Adherence and Visual Field Progression in the Collaborative Initial Glaucoma Treatment Study
    Ophthalmology (IF 7.732) Pub Date : 2020-01-10
    Paula Anne Newman-Casey; Leslie M. Niziol; Brenda W. Gillespie; Nancy K. Janz; Paul R. Lichter; David C. Musch

    Purpose To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma. Participants Three hundred seven participants randomized to the medication arm of the CIGTS. Methods Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, “Did you happen to miss any dose of your medication yesterday?” The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported. Main Outcome Measure Mean deviation over time. Results Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17–1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86–1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19–3.26; P < 0.0001). Conclusions This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss.

    更新日期:2020-01-11
  • Biallelic CPAMD8 variants are a frequent cause of childhood and juvenile open-angle glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2020-01-07
    Owen M. Siggs; Emmanuelle Souzeau; Deepa A. Taranath; Andrew Dubowsky; Angela Chappell; Tiger Zhou; Shari Javadiyan; Jillian Nicholl; Lisa S. Kearns; Sandra E. Staffieri; Andrew Narita; James EH. Smith; John Pater; Alex W. Hewitt; Jonathan B. Ruddle; James E. Elder; David A. Mackey; Kathryn P. Burdon; Jamie E. Craig

    Purpose Developmental abnormalities of the ocular anterior segment can, in some cases, lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma. Design Retrospective multicenter case series. Participants Two hundred and sixty-eight probands and their relatives with a diagnosis of childhood or juvenile open-angle glaucoma. Methods Patients underwent a comprehensive ophthalmic assessment, with DNA from patients and their relatives subjected to genome, exome, or capillary sequencing. CPAMD8 RNA expression analysis was performed on tissues dissected from cadaveric human eyes. Main Outcome Measures Diagnostic yield within a cohort of childhood and juvenile open-angle glaucoma, prevalence and risk of ophthalmic phenotypes, and relative expression of CPAMD8 in the human eye. Results We identified rare (allele frequency < 4 x 10-5) biallelic CPAMD8 variants in 5.7% (5/88) of probands with childhood glaucoma, and 2.1% (2/96) of probands with juvenile open-angle glaucoma. When including family members, we identified a total of eleven individuals with biallelic variants in CPAMD8 from seven unrelated families. Nine of these individuals were diagnosed with glaucoma (9/11, 81.8%), with a mean age at diagnosis of 9.22 ± 14.89 years, and all individuals with glaucoma required one or more incisional procedures to control high intraocular pressure. Iris abnormalities were observed in 9/11 individuals, cataract in 8/11 (72.7%), and retinal detachment in 3/11 (27.3%). CPAMD8 expression was highest in neural crest-derived tissues of the adult anterior segment, suggesting that CPAMD8 variation may cause malformation or obstruction of key drainage structures. Conclusions Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype, and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1, and juvenile open-angle glaucoma after MYOC. CPAMD8 sequencing should be considered in the investigation of both childhood and juvenile open-angle glaucoma, particularly when associated with iris abnormalities, cataract, or retinal detachment.

    更新日期:2020-01-07
  • An intraocular pressure polygenic risk score stratifies multiple primary open angle glaucoma parameters including treatment intensity
    Ophthalmology (IF 7.732) Pub Date : 2020-01-07
    Ayub Qassim; Emmanuelle Souzeau; Owen M. Siggs; Mark M. Hassall; Xikun Han; Helen L. Griffiths; N Andrew Frost; Neeru A. Vallabh; James F. Kirwan; Geeta Menon; Angela J. Cree; Anna Galanopoulos; Ashish Agar; Paul R. Healey; Stuart L. Graham; John Landers; Robert J. Casson; Puya Gharahkhani; Jamie E. Craig

    Objective To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. Design Cross-sectional study. Participants For the primary analysis, we examined the glaucoma phenotype of 2,154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) including cases recruited from the UK. For replication, we examined an independent cohort of 624 early POAG patients. Methods Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP associated variants and stratified POAG patients into three risk tiers. The lowest and highest quintiles of the score were set as the low and high risk groups respectively and the other quintiles as the intermediate risk group. Main Outcome Measures Clinical glaucoma phenotype including maximum recorded IOP, age of diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. Results There was a dose-response relationship between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 (SD 0.62) mmHg than the low genetic risk group (P = 0.006). Compared to the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 (1.0) years (P < 0.001), more family members affected by 0.46 (0.11) members (P < 0.001), and higher rates of incisional surgery (odds ratio 1.5; 95% confidence interval 1.1 - 2.0; P = 0.007). There was no statistically significant difference in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). Conclusions The IOP polygenic risk score was positively correlated with maximum IOP, disease severity, need for surgery and number of family members. Genes acting via IOP mediated pathways, when considered in aggregate have clinically important and reproducible implications for glaucoma patients and their close family members.

    更新日期:2020-01-07
  • Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair
    Ophthalmology (IF 7.732) Pub Date : 2019-12-30
    Jeremiah P. Tao; Vinay K. Aakalu; Edward J. Wladis; Rachel K. Sobel; Suzanne K. Freitag; Jill A. Foster; Michael T. Yen

    Purpose To review the literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair. Methods A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019 to identify all studies in the English language literature on the use of BADM grafts in eyelid reconstruction. The searches yielded 193 citations, and 15 of the 34 articles selected for full review met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Two of the 15 studies included were rated level II and 13 were rated level III. Results The definition of success varied, but lower eyelid position improvement using lower lid margin-to-pupillary reflex distance was the most common outcome measure. Other end points were the amount of lagophthalmos, cosmesis, exposure, reoperation, or complications, as well as prosthesis retention in anophthalmic socket cases. The surgeon-reported success rate of these outcomes ranged from 75% to 100%. Minor complications included cyst formation, infection, chemosis, pyogenic granuloma, and corneal abrasion. No serious complications such as blindness, anaphylactic reaction, or terminal disease transmission occurred. Of the 526 implants included for assessment in these disparate studies, 27 cases (5%) required reoperation. Conclusions No level I evidence was available, and the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up data. The current literature suggests that BADM grafts represent an implantation option for lower eyelid retraction repair. Short-term results are favorable, and the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown.

    更新日期:2019-12-30
  • The Ocular Surface Frailty Index as a predictor of ocular surface symptoms onset after cataract surgery
    Ophthalmology (IF 7.732) Pub Date : 2019-12-28
    Edoardo Villani; Luca Marelli; Francesco Bonsignore; Stefano Lucentini; Saverio Luccarelli; Matteo Sacchi; Massimiliano Serafino; Paolo Nucci

    Purpose The identification of healthy subjects more susceptible to develop post-surgical ocular surface symptoms is still an unmet need. We performed this study to build a new Ocular Surface Frailty Index (OSFI) and to assess its predictive value for dry eye (DED) symptoms onset after cataract surgery. Design Single-centre, observational, longitudinal study. Participants We screened 405 consecutive patients scheduled for phacoemulsification for age-related cataract. 284 eyes of 284 patients without pre-operative DED symptoms who underwent uneventful cataract surgery were included in the analysis. Methods Borrowing a concept from geriatric surgery and following a previously validated procedure, we built a tool to assess ocular surface frailty. Starting from a preliminary list of 19 potential items, the final OSFI, including 10 “deficits in ocular surface health and/or factors potentially able to affect it”, was developed by a stepwise approach. Pre-operative OSFI was calculated for each enrolled patient and diagnostic tests for DED were performed (following the TFOS DEWS II recommendations) at the screening visit and 1 week (V1), 1 month (V2), and 3 months (V3) after surgery. We evaluated OSFI predictivity for the presence of DED symptoms at V2 AND/OR V3. Main Outcome Measures The rate of ocular surface symptoms at V2 AND/OR V3. Results Our patients’ OSFI score ranged from 0 to 0.666, with a median value of 0.200 (0.133-0.266). The percentage of patients with post-surgical ocular surface symptoms was 17%. Using an OSFI cut-off of 0.300, we identified a small group (19% of the asymptomatic subjects) of patients with frail ocular surfaces, who had a significantly higher risk to develop post-surgical DED symptoms (50.0% vs 9.6%; P<0.001, χ2 test). Logistic regression analysis showed that OSFI≥0.3 (but not age, gender or any pre-operative sign) was a good predictor of ocular surface symptoms onset (odds ratio (OR) =9.45; 95%CI (4.74-18.82). Regression was still significant when performed on 200 bootstrapped samples. Conclusions The OSFI can be easily and quickly calculated using non-invasive and low-tech procedures and it showed to be predictive of post-operative ocular surface symptoms onset. This novel tool might allow cataract surgeons to perform a useful pre-operative personalized risk assessment.

    更新日期:2019-12-29
  • Ocular Anesthesia-Related Closed Claims from Ophthalmic Mutual Insurance Company 2008-2018
    Ophthalmology (IF 7.732) Pub Date : 2019-12-25
    Michael Morley; Anne M. Menke; Karen C. Nanji

    Purpose To evaluate the types of anesthesia-related closed claims and their contributing factors, using data from Ophthalmic Mutual Insurance Company (OMIC). Design Retrospective analysis of pre-existing data Participants Plaintiffs who filed a professional liability claim or suit (written demand for money) against OMIC-insured ophthalmologists, ophthalmic practices, and/or surgicenters in which the surgical case occurred. Methods Plaintiff claims were collected from the OMIC database from 2008-2018 using search queries for terms associated with known complications of ophthalmic anesthesia. Main outcome measures Number and types of anesthesia-related injuries and claims, who administered the anesthesia, the outcomes of the claim or suit, cost to defend, and payments made to plaintiffs. Results Sixty-three anesthesia related claims or suits were filed by 50 plaintiffs. Anesthesia-related injuries included globe perforation (n=17), death (n=13), retrobulbar hemorrhage (n=7), optic nerve damage (n=4), vascular occlusions (n=2), pain (n=2), eye or head movement resulting in injury (n=2), and one case each for numbness, diplopia, and tooth loss during intubation. All but 1 patient who died had pre-existing, significant co-morbidities. Two deaths were related to brainstem anesthesia. Regarding the type of anesthesia in the closed claims, retrobulbar and peribulbar anesthesia were the most common types (n=16 each ), followed by local infiltration around the lids and facial nerve (n=6), topical anesthesia (n=5) and general anesthesia (n=5). In two cases, the exact type of anesthesia was unknown but not general. The 5 topical with sedation anesthesia-related claims were due to inadequate pain control (n= 2), ocular movement resulting in capsular rupture (n= 2), or death (n=1) allegedly related to excessive, or inadequate monitoring of, sedation. There were 5 claims related to general anesthesia including 4 deaths and 1 tooth loss during intubation. Sedation was alleged to be a factor in 5 cases resulting in death. Anticoagulants were a factor in 3 retrobulbar hemorrhage cases. Conclusions While claims and suits were infrequent given the large number of insured ophthalmologists and the large number of surgical cases requiring various types of anesthesia performed over the 10.5-year study period, severe injuries can occur.

    更新日期:2019-12-26
  • Eye Injuries in the National Basketball Association
    Ophthalmology (IF 7.732) Pub Date : 2019-12-23
    Jonathan A. Go; Sophie Y. Lin; Katherine J. Williams; Jeffrey Tran; Adam R. Sweeney; Rod Foroozan; Michael T. Yen

    Eye injuries in the National Basketball Association during the 2018-2019 regular season are not uncommon and resulted in significant negative financial and performance impacts to teams.

    更新日期:2019-12-23
  • Beyond Performance Metrics: Automatic Deep Learning Retinal OCT Analysis Reproduces Clinical Trial Outcome
    Ophthalmology (IF 7.732) Pub Date : 2019-12-23
    Jessica Loo; Traci E. Clemons; Emily Y. Chew; Martin Friedlander; Glenn J. Jaffe; Sina Farsiu

    Purpose To validate the efficacy of a fully-automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2) Design Evaluation of diagnostic test or technology Participants 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to one of two treatment groups Methods The ellipsoid zone (EZ) defect areas were measured on spectral domain optical coherence tomography images of each eye at two time points (Baseline and Month 24) by a fully-automatic, deep learning-based segmentation algorithm. The change in EZ defect area from Baseline to Month 24 was calculated and analyzed according to the clinical trial protocol. Primary Outcome Measure Difference in the change in EZ defect area from Baseline to Month 24 between the two treatment groups. Results The difference in the change in EZ defect area from Baseline to Month 24 between the two treatment groups measured by the fully-automatic segmentation algorithm was 0.072 ± 0.035 mm2 (p = 0.021). This was comparable to the outcome of the clinical trial using semi-automatic measurements by expert Readers, 0.065 ± 0.033 mm2 (p = 0.025). Conclusions The fully-automatic segmentation algorithm was as accurate as semi-automatic expert segmentation to assess EZ defect areas and was able to reliably reproduce the statistically significant primary outcome measure of the clinical trial. This approach, to validate the performance of an automatic segmentation algorithm on the primary clinical trial endpoint, provides a robust gauge of its clinical applicability.

    更新日期:2019-12-23
  • Two-Year Clinical Trial of the Low-concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report
    Ophthalmology (IF 7.732) Pub Date : 2019-12-21
    Jason C. Yam; Fen Fen Li; Xiujuan Zhang; Shu Min Tang; Benjamin Hon Kei Yip; Ka Wai Kam; Simon T. Ko; Alvin L. Young; Clement C. Tham; Li Jia Chen; Chi Pui Pang

    Purpose To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drop over 2 years to determine which is the optimal concentration for longer-term myopia control. Design A randomized, double-masked trial, extended from the Low-Concentration Atropine for Myopia Progression (LAMP) study. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials disclosed in this article. Participants Three hundred eighty-three (87%) of the 438 children aged 4 to 12 years with myopia of at least -1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2). Methods Children of the placebo group in phase 1 were switched to receive 0.05% atropine from the beginning of the second year follow up, while those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals. Main outcome measure Changes in spherical equivalent (SE) and AL, and their differences between groups. Results Over the 2-year period, the mean SE progression was 0.55±0.86D, 0.85±0.73D, and 1.12±0.85D in the 0.05%, 0.025%, 0.01% atropine groups, respectively (P=0.015, P<.001, and P=0.02 for pairwise comparisons); with mean AL changes over two years of 0.39±0.35mm, 0.50±0.33mm, and 0.59±0.38mm (P=0.04, P<0.001, and P=0.10). Compared with the 1st year, the 2nd year efficacy of 0.05% and 0.025% remained similar (p=0.45 and p=0.31), but mildly improved in the 0.01% atropine group (P=0.04). For the phase 1 placebo group, the myopia progression was significantly reduced after switching to 0.05% atropine (SE change 0.18D in second year vs. 0.82D in first year, p<0.001; AL elongated 0.15mm in second year vs 0.43mm in first year, p<0.001). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results, and were well tolerated. Visual acuity, and vision related quality of life remained unaffected. Conclusions Over two years, the observed efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration amongst the studied atropine concentrations in slowing myopia progression.

    更新日期:2019-12-21
  • A Prospective Randomized Trial Comparing Hydrus and iStent Microinvasive Glaucoma Surgery Implants for Standalone Treatment of Open-Angle Glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2019-04-26
    Iqbal Ike K. Ahmed; Antonio Fea; Leon Au; Robert E. Ang; Paul Harasymowycz; Henry D. Jampel; Thomas W. Samuelson; David F. Chang; Douglas J. Rhee

    Purpose To compare the efficacy of different microinvasive glaucoma surgery (MIGS) devices for reducing intraocular pressure (IOP) and medications in open-angle glaucoma (OAG). Design Prospective, multicenter, randomized clinical trial. Participants One hundred fifty-two eyes from 152 patients aged 45 to 84 years with OAG, Shaffer angle grade III–IV, best-corrected visual acuity (BCVA) 20/30 or better, and IOP 23 to 39 mmHg after washout of all hypotensive medications. Eyes with secondary glaucoma other than pseudoexfoliative or pigmentary glaucoma, angle closure, previous incisional glaucoma surgery, or any significant ocular pathology other than glaucoma were excluded. Intervention Study eyes were randomized 1:1 to standalone MIGS consisting of either 1 Hydrus Microstent (Ivantis, Inc, Irvine, CA) or 2 iStent Trabecular Micro Bypass devices (Glaukos Inc, San Clemente, CA). Follow-up was performed 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. Main Outcome Measures Within-group and between-group differences in IOP and medications at 12 months and complete surgical success defined as freedom from repeat glaucoma surgery, IOP 18 mmHg or less, and no glaucoma medications. Safety measures included the frequency of surgical complications, changes in visual acuity, slit-lamp findings, and adverse events. Results Study groups were well matched for baseline demographics, glaucoma status, medication use, and baseline IOP. Twelve-month follow-up was completed in 148 of 152 randomized subjects (97.3%). At 12 months, the Hydrus had a greater rate of complete surgical success (P < 0.001) and reduced medication use (difference = −0.6 medications, P = 0.004). More Hydrus subjects were medication free at 12 months (difference = 22.6% P = 0.0057). Secondary glaucoma surgery was performed in 2 eyes in the 2-iStent group (3.9%) and in none of the Hydrus eyes. Two eyes in the Hydrus group and 1 in the 2-iStent group had BCVA loss of ≥2 lines. Conclusion Standalone MIGS in OAG with the Hydrus resulted in a higher surgical success rate and fewer medications compared with the 2-iStent procedure. The 2 MIGS devices have similar safety profiles.

    更新日期:2019-12-18
  • HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration
    Ophthalmology (IF 7.732) Pub Date : 2019-04-12
    Pravin U. Dugel; Adrian Koh; Yuichiro Ogura; Glenn J. Jaffe; Ursula Schmidt-Erfurth; David M. Brown; Andre V. Gomes; James Warburton; Andreas Weichselberger; Frank G. Holz

    Purpose Two similarly designed phase 3 trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration (nAMD). Design Double-masked, multicenter, active-controlled, randomized trials. Participants Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye. Intervention Patients were randomized to intravitreal brolucizumab 3 mg (HAWK only) or 6 mg or aflibercept 2 mg. After loading with 3 monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval adjusted to every 8 weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing. Main Outcome Measures The primary hypothesis was noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to Week 48 (margin: 4 letters). Other key end points included the percentage of patients who maintained q12w dosing through Week 48 and anatomic outcomes. Results At Week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; P < 0.001 for each comparison). Greater than 50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]). At Week 16, after identical treatment exposure, fewer brolucizumab 6 mg–treated eyes had disease activity versus aflibercept in HAWK (24.0% vs. 34.5%; P = 0.001) and HARRIER (22.7% vs. 32.2%; P = 0.002). Greater central subfield thickness reductions from baseline to Week 48 were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean −172.8 μm vs. −143.7 μm; P = 0.001) and HARRIER (LS mean −193.8 μm vs. −143.9 μm; P < 0.001). Anatomic retinal fluid outcomes favored brolucizumab over aflibercept. Overall, adverse event rates were generally similar with brolucizumab and aflibercept. Conclusions Brolucizumab was noninferior to aflibercept in visual function at Week 48, and >50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing interval through Week 48. Anatomic outcomes favored brolucizumab over aflibercept. Overall safety with brolucizumab was similar to aflibercept (ClinicalTrials.gov; NCT02307682, NCT02434328).

    更新日期:2019-12-18
  • Development and Validation of Deep Learning Models for Screening Multiple Abnormal Findings in Retinal Fundus Images
    Ophthalmology (IF 7.732) Pub Date : 2019-05-31
    Jaemin Son; Joo Young Shin; Hoon Dong Kim; Kyu-Hwan Jung; Kyu Hyung Park; Sang Jun Park

    Purpose To develop and evaluate deep learning models that screen multiple abnormal findings in retinal fundus images. Design Cross-sectional study. Participants For the development and testing of deep learning models, 309 786 readings from 103 262 images were used. Two additional external datasets (the Indian Diabetic Retinopathy Image Dataset and e-ophtha) were used for testing. A third external dataset (Messidor) was used for comparison of the models with human experts. Methods Macula-centered retinal fundus images from the Seoul National University Bundang Hospital Retina Image Archive, obtained at the health screening center and ophthalmology outpatient clinic at Seoul National University Bundang Hospital, were assessed for 12 major findings (hemorrhage, hard exudate, cotton-wool patch, drusen, membrane, macular hole, myelinated nerve fiber, chorioretinal atrophy or scar, any vascular abnormality, retinal nerve fiber layer defect, glaucomatous disc change, and nonglaucomatous disc change) with their regional information using deep learning algorithms. Main Outcome Measures Area under the receiver operating characteristic curve and sensitivity and specificity of the deep learning algorithms at the highest harmonic mean were evaluated and compared with the performance of retina specialists, and visualization of the lesions was qualitatively analyzed. Results Areas under the receiver operating characteristic curves for all findings were high at 96.2% to 99.9% when tested in the in-house dataset. Lesion heatmaps highlight salient regions effectively in various findings. Areas under the receiver operating characteristic curves for diabetic retinopathy-related findings tested in the Indian Diabetic Retinopathy Image Dataset and e-ophtha dataset were 94.7% to 98.0%. The model demonstrated a performance that rivaled that of human experts, especially in the detection of hemorrhage, hard exudate, membrane, macular hole, myelinated nerve fiber, and glaucomatous disc change. Conclusions Our deep learning algorithms with region guidance showed reliable performance for detection of multiple findings in macula-centered retinal fundus images. These interpretable, as well as reliable, classification outputs open the possibility for clinical use as an automated screening system for retinal fundus images.

    更新日期:2019-12-18
  • The Relative Impact of Patient, Physician, and Geographic Factors on Variation in Primary Rhegmatogenous Retinal Detachment Management
    Ophthalmology (IF 7.732) Pub Date : 2019-04-12
    Daniel Vail; Suzann Pershing; Mary-Grace Reeves; Armin R. Afshar

    Purpose To evaluate geographic variation and characterize the relative contributions of patient characteristics, physician practice, and geographic region on variation in primary rhegmatogenous retinal detachment (RRD) management. Design Retrospective claims-based analysis. Participants Commercially insured patients with incident RRD diagnosed between 2008 and 2016 (12 779 patients). Methods We determined whether patients underwent primary RRD repair within 60 days of diagnosis and identified repair type. We characterized physicians using physician identifier variables and characterized geography by Combined Statistical Areas or Core-Based Statistical Area. We used multilevel mixed effects logistic regression models to evaluate patient-, physician-, and geographic-level variation in whether patients underwent RRD repair and used multilevel mixed effects multinomial models to characterize variation in repair type. For each model, we evaluated patient fixed effects and physician random effects nested within geographic random effects. We estimated intraclass correlation coefficients and variance partition coefficients, respectively, to compare relative contributions of patient, physician, and geography to overall variation. Main Outcome Measures Odds ratios for RRD repair and variation estimates for patient, physician, and geography. Results Most incident RRD patients received treatment within 60 days post-diagnosis. Pars plana vitrectomy was most common (49%), followed by laser barricade (23%), scleral buckle and pneumatic retinopexy (both 11%), and cryotherapy (5%). Physician-level variation showed greater impact on receipt of any treatment than geographic-level variation (estimated variance coefficients of 1.09 and 0.32, respectively). Patient-level characteristics represented approximately 82% of overall variation in receipt of any repair, versus 16% from physician-level and 2% from geographic-level factors. Among RRD patients who underwent repair, estimated variance coefficients were 0.07 for geography and 3.37 for physician. Physician-level factors represented approximately 50% of total variation in repair type, followed by patient-level (49%), and geographic-level (1%) factors. Conclusions Rhegmatogenous retinal detachment repair decisions are influenced by patient-level and physician-level factors, less so by geographic variation. Patient characteristics account for most of the variation in receipt of repair, and physician practice accounts for most of the variation in choice of procedure. These findings indicate a need for additional studies to understand drivers behind differences in care and clinical outcomes and to identify barriers in access to care.

    更新日期:2019-12-18
  • Quantitative Assessment of the Retina Using OCT and Associations with Cognitive Function
    Ophthalmology (IF 7.732) Pub Date : 2019-06-04
    Yoshikazu Ito; Mariko Sasaki; Hiroki Takahashi; Shoko Nozaki; Shinichiro Matsuguma; Kaoru Motomura; Rihito Ui; Ryo Shikimoto; Ryo Kawasaki; Kenya Yuki; Norie Sawada; Masaru Mimura; Kazuo Tsubota; Shoichiro Tsugane

    Purpose To determine the association of retinal thickness with cognitive function in Japanese persons. Design Cross-sectional, population-based survey. Participants A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center–Based Prospective Study participated in the eye and mental health screening. Methods Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors. Main Outcome Measures Association of retinal thickness with cognitive function. Results Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors. Conclusions Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function.

    更新日期:2019-12-18
  • Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials
    Ophthalmology (IF 7.732) Pub Date : 2019-12-14
    Nancy Holekamp; Charles C. Wykoff; Steffen Schmitz-Valckenberg; Jordi Monés; Eric H. Souied; Hugh Lin; Melvin D. Rabena; Ronald A. Cantrell; Erin C. Henry; Fan Tang; Balakumar Swaminathan; Jillian Martin; Daniela Ferrara; Giovanni Staurenghi

    Purpose To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design Proxima A (NCT02479386) and Proxima B (NCT02399072) were global, prospective, non-interventional, observational clinical trials. Participants Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N=295). Patients in Proxima B had GA with no CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n=168); or GA with no CNV in the study eye, without CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n=32). Methods Changes in visual function and imaging/anatomic parameters were evaluated over time using a Mixed Model for Repeated Measurement (MMRM) accounting for key baseline characteristics. Main Outcome Measures Pre-specified endpoints included change in GA area from baseline, best corrected visual acuity (BCVA) score assessed by ETDRS, and BCVA under low-luminance conditions (LLVA). Results At 24 months, the adjusted mean (standard error; SE) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). GA progression was greater in patients with baseline non-subfoveal (vs. subfoveal) GA lesions, and tended to increase as baseline low-luminance deficit increased (Proxima A; Proxima B, all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (SE) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months: −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in the Proxima B fellow eye CNV cohort, −11.48 (3.39) and −8.37 (3.02) in the Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

    更新日期:2019-12-17
  • Artificial Intelligence Classification of Central Visual Field Patterns in Glaucoma
    Ophthalmology (IF 7.732) Pub Date : 2019-12-12
    Mengyu Wang; Lucy Q. Shen; Louis R. Pasquale; Michael V. Boland; Sarah R. Wellik; Carlos Gustavo De Moraes; Jonathan S. Myers; Thao Nguyen; Robert Ritch; Pradeep Ramulu; Hui Wang; Jorryt Tichelaar; Dian Li; Peter J. Bex; Tobias Elze

    Purpose To quantify the central visual field (VF) loss patterns in glaucoma using machine-learning. Design Retrospective study. Participants 8,712 patients with 13,951 Humphrey 10-2 tests from 13,951 eyes for cross-sectional analyses, and 824 patients with at least five reliable 10-2 tests at 6 or more month intervals from 1191 eyes for longitudinal analyses. Methods Total deviation values were used to determine the central VF patterns using the most recent 10-2 tests. A 24-2 VF within a 3 month window of the 10-2 tests was used to stage eyes into mild, moderate or severe functional loss using the Hodapp-Anderson-Parrish scale at baseline. Archetypal analysis was applied to determine the central VF patterns. Cross-validation was performed to determine the optimal number of patterns. Stepwise regression was applied to select the optimal feature combination of global indices, average baseline decomposition coefficients from central VFs archetypes and other factors to predict central VF mean deviation (MD) slope based on the Bayesian information criterion (BIC). Main Outcome Measures The central VF patterns stratified by severity stage based on 24-2 tests and a model to predict the central VF MD change over time using baseline tests. Results From cross-sectional analysis, 17 distinct central VF patterns were determined for the 13,951 eyes across the spectrum of disease severity. These central VF patterns could be divided into isolated superior loss, isolated inferior loss, diffuse loss and other loss patterns. Notably, 4 of the 5 patterns of diffuse VF loss preserved the less vulnerable inferotemporal zone, while they lost most of the remaining more vulnerable zone described by the Hood model. Inclusion of coefficients from central VFs archetypical patterns strongly improved the prediction of central VF MD slope (BIC decreasing of 35; BIC decreasing > 6 indicating strong prediction improvement) than using only the global indices of two baseline VFs. Eyes with baseline VFs with more superonasal and inferonasal loss were more likely to have worsening MD over time. Conclusion We quantified central VF patterns in glaucoma, which were used to improve the prediction of central VF worsening compared with only using global indices alone.

    更新日期:2019-12-13
  • Next-generation sequencing of retinoblastoma identifies pathogenic alterations beyond RB1 inactivation that correlate with aggressive histopathologic features
    Ophthalmology (IF 7.732) Pub Date : 2019-12-12
    Armin R. Afshar; Melike Pekmezci; Michele M. Bloomer; Nicola J. Cadenas; Meredith Stevers; Anuradha Banerjee; Ritu Roy; Adam B. Olshen; Jessica Van Ziffle; Courtney Onodera; Patrick Devine; James P. Grenert; Boris C. Bastian; David A. Solomon; Bertil E. Damato

    Objective To determine the utility of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. Design Cohort study. Subjects 32 children with retinoblastoma. Methods We performed targeted NGS using the UCSF500 Cancer Panel on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. Main Outcome Measures Presence or absence of germline RB1 mutation/deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. Results Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n=12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification in 4 tumors (two with wildtype RB1 and two with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been previously reported in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. Conclusions Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlate with aggressive histopathologic features.

    更新日期:2019-12-13
  • Myopia and Childhood Migration: A Study of 607,862 Adolescents
    Ophthalmology (IF 7.732) Pub Date : 2019-12-09
    Alon Peled, Arnon Afek, Gilad Twig, Eran Pras, Ygal Rotenstreich, Ifat Sher, Estela Derazne, Dorit Tzur, Barak Gordon

    Purpose Immigrational studies can shed light on myopia development and reveal high-risk populations. To this end, we investigated the association between immigration, age at immigration, and myopia occurrence at adolescence. Design Population-based, retrospective, cross-sectional study. Participants 607,862 adolescents, Israeli-born and immigrants, with origins in the former Union of Soviet Socialist Republics (USSR), Ethiopia or Israeli-natives, assessed for medical fitness for mandatory military service at age 17 years between 1993 and 2016. Methods Refraction was determined using subjective visual acuity followed by noncycloplegic autorefraction and subjective validation. Myopia was defined as -0.75 diopters myopia or worse in each principal meridian in the right eye. High myopia was defined as -0.75 diopters myopia or worse in each principal meridian and a spherical equivalent of -6.00 D or worse, in the right eye. Age at immigration was categorized into 0-5, 6-11 and 12-19 years. Univariate and multivariable logistic regression models were made. Myopia odds ratios (ORs) were calculated according to immigrational status, with Israel-natives as controls. Next, myopia ORs were calculated according to age at immigration, with Israeli-born of same origin as controls. Main Outcome Measures Myopia prevalence and ORs Results Myopia was less prevalent among immigrants than among Israeli-natives. When stratified according to age at immigration, a decrease in myopia prevalence and ORs with increasing age at migration categories was observed, most prominent in immigrants arriving after age 11 years, who also had lower high myopia ORs. USSR and Ethiopian immigrants arriving after age 11 years had myopia OR of 0.65 (95% CI 0.63-0.67; p< 10-205) and 0.52 (95% CI 0.46-0.58; p<10-27) compared to the Israeli-born of same origin. Notably, Ethiopians arriving earlier than age 5 had a two-fold myopia OR than those migrating after age 11. Conclusion Immigrants arriving after age 11 years had marked lower ORs for myopia and high myopia relative to the Israeli-born or to those arriving at early childhood, likely due to environmental and lifestyle changes. Differences between immigrants arriving until age 5 to those arriving between 6-11 years were relatively smaller, suggesting exposures at elementary-school age play a greater role in our population.

    更新日期:2019-12-09
  • PREDICTORS OF LONG-TERM VISUAL FIELD FLUCTUATION IN GLAUCOMA PATIENTS
    Ophthalmology (IF 7.732) Pub Date : 2019-12-05
    Alessandro Rabiolo, Esteban Morales, Ji Hyun Kim, Abdelmonem A. Afifi, Fei Yu, Kouros Nouri-Mahdavi, Joseph Caprioli

    Purpose To identify predictive factors for visual field (VF) fluctuation in glaucoma patients. Design Retrospective cohort study. Subjects A total of 1,392 eyes (816 patients) with ≥6 VFs and ≥3 years of follow-up. Methods For each eye, the VF mean deviation (MD) was regressed against time to model the series trend, and the root mean square error (RMSE) was estimated as a measure of variability. Similarly, the threshold sensitivity at individual test locations was regressed against time, residuals for a single eye pooled, and the RMSE calculated. The following baseline variables were tested as potential predictors: age, gender, eye laterality, ethnicity, intraocular pressure (IOP), central corneal thickness, number of glaucoma medications, spherical equivalent, best-corrected visual acuity, lens status, previous glaucoma surgery, MD, hypertension, diabetes, smoking, and family history of glaucoma. The following longitudinal variables were tested: IOP fluctuation, length of follow-up, frequency of VFs, glaucoma/cataract surgery, rate of VF decay, and median false positive (FP), false negative (FN), and fixation loss rates. Variables were selected with LASSO regression. Main Outcome Measures Predictors of global and pointwise VF long-term fluctuation. Results In the global model, left eye (0.063 dB, p=0.022), Asian descent (0.265 dB, p=0.006), larger IOP fluctuation (0.051 dB, p<0.001), intervening cataract surgery (0.090 dB, p=0.023), longer follow-up (0.130 dB, p<0.001), worse baseline MD (–0.145 dB, p<0.001), faster VF decay rates (–0.090 dB, p<0.001), and higher FPs (0.145 dB, p<0.001) and FNs (0.220 dB, p<0.001) were predictors of VF fluctuation. In the pointwise model, larger IOP fluctuation (0.039 dB, p=0.022), longer follow-up (0.340 dB, p<0.001), higher VFs frequency (0.238 dB, p=0.002), intervening glaucoma surgery (0.190 dB, p=0.01), worse baseline MD (–0.535 dB, p<0.001), faster VF decay rates (–0.340 dB, p<0.001), and higher FPs (0.255 dB, p<0.001) and FNs (0.395 dB, p <0.001) were associated with increased fluctuation. The multivariable model explained 57% and 28% of the pointwise and global variances, respectively. Conclusion This study identifies novel predictors of VF fluctuation. Nearly 60% of the pointwise variance can be explained by a multivariable model. In the presence of factors predictive of high fluctuation, increased frequency of testing and better analytics will help identify VF progression more accurately.

    更新日期:2019-12-05
  • Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis. Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group
    Ophthalmology (IF 7.732) Pub Date : 2019-12-02
    Victor Llorenç, Miguel Cordero-Coma, Ana Blanco-Esteban, Henar Heras-Mulero, María-José Losada-Castillo, Vega Jovani-Casano, Elia Valls-Pascual, Margarita Jodar-Marquez, Ángel García-Aparicio, Alejandro Fonollosa, Juan Jacobo González-Guijarro, Luís Rodriguez-Melian, Manuel Fernández-Prada, María Jerez-Fidalgo, Marisa Hernandez-Garfella, Cristina Esquinas, Maite Sainz-de-la-Maza, Alfredo Adán

    Purpose To study drug retention rate (DRR), causes and predictors of discontinuation of adalimumab (ADA) in real-world uveitis setting. Design Multicentric, nation-wide, registry-based, ambispective, observational study. Subjects Patients treated with ADA for non-infectious uveitis in the Biotherapies for Uveitis (BioÚvea) Spanish registry from Nov 2016 to Nov 2017. Methods Demographics, clinical data, timing and reasons for discontinuation, if occurred, were recorded. DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional hazards model and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. Main Outcome Measures DRR and DRT. Results 392 patients were analyzed, including 218 females. Median age was 39 (IQR 25) years. Non-anterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. DRR at 6, 12, 24 and 60 months was 92.97%, 87.68%, 76.31% and 54.28%, respectively. ADA was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74, adverse event in 34, and sustained quiescence in 25 patients. Recorded adverse events included: infections in 10 patients and malignant neoplasms in 3. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. ADA was prescribed as a ≥2nd biotherapy line in 76 patients, who showed shorter DRT (p=0.038). Starting ADA in non-biotherapy-naïve patients was a predictor for “discontinuation due to inefficacy”, whereas undifferentiated uveitis was a predictor for “discontinuation due to adverse event”. DRT was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. Conclusions DRR of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show significant influence on DRT. The use of ADA as a second or more biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.

    更新日期:2019-12-03
  • Return To The Operating Room For Removal Of Retained Lens Fragments After Cataract Surgery: Iris® Registry Analysis
    Ophthalmology (IF 7.732) Pub Date : 2019-11-29
    Michael A. Mahr, Flora Lum, Danielle Fujino, Scott P. Kelly, Jay C. Erie

    A retrospective IRIS Registry-based study of over 2.26 million patients undergoing cataract surgery in the US shows that 0.18% (1 in 563) returned to the operating room for secondary removal of retained lens fragments in the anterior chamber within one year of the original surgery. The risk of secondary removal of retained lens fragments was increased among complex coded cataract surgery, males, smokers, and in patients with military or Medicaid insurance status.

    更新日期:2019-11-29
  • Factors Predictive of Remission of Chronic Anterior Uveitis
    Ophthalmology (IF 7.732) Pub Date : 2019-11-28
    Lucia Sobrin, Maxwell Pistilli, Kurt Dreger, Srishti Kothari, Naira Khachatryan, Pichaporn Artornsombudh, Siddharth S. Pujari, C. Stephen Foster, Douglas A. Jabs, Robert B. Nussenblatt, James T. Rosenbaum, Grace A. Levy-Clarke, H. Nida Sen, Eric B. Suhler, Jennifer E. Thorne, Nirali P. Bhatt, John H. Kempen

    Purpose To estimate the incidence of medication-free remission of chronic anterior uveitis; to identify predictors thereof. Design Retrospective cohort study Participants Patients diagnosed as having anterior uveitis for greater than 3 months followed at United States tertiary uveitis care facilities Methods Retrospective cohort study based on standardized chart review. Estimation of remission incidence and identification of associated predictors used survival analysis. Main Outcome Measures Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis off treatment at all visits spanning an interval of at least 90 days or—for patients who did not return for follow-up after 90 days—remaining inactive without receiving suppressive medications at all of their last visits. Association of factors potentially predictive of medication-free remission also was studied. Results 2795 eyes of 1634 patients with chronic anterior uveitis were followed over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% [95% Confidence Interval (CI), 30.4% - 35.2%]. Baseline clinical factors predictive of less remission included longer duration of uveitis at presentation [adjusted hazard ratio (aHR), 0.61; 95% CI, 0.44 - 0.83; for 2 - 5 years vs. less than 6 months], bilateral uveitis (aHR, 0.75, 95% CI, 0.59 – 0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56 – 0.88) and glaucoma surgery (aHR, 0.63; 95% CI, 0.45 – 0.90). Two time-updated characteristics were also predictive of less remission: keratic precipitates (aHR, 0.36; 95% CI 0.21– 0.60) and synechiae (aHR, 0.62; 95% CI, 0.41 - 0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy also were associated with less remission. Older age at presentation was associated with higher incidence of remission (aHR, 1.29; 95%, CI 1.02 – 1.63, for age ≥ 40 years vs. < 40 years). Conclusions Approximately one-third of chronic anterior uveitis cases remit within five years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict less remission; cases with these factors should be managed taking into account the higher probability of a longer disease course.

    更新日期:2019-11-29
  • Incidence of macular atrophy following untreated neovascular age-related macular degeneration: Age-Related Eye Disease Study Report 40
    Ophthalmology (IF 7.732) Pub Date : 2019-11-26
    Panos G. Christakis, Elvira Agrón, Michael L. Klein, Traci E. Clemons, J. Peter Campbell, Frederick L. Ferris, Emily Y. Chew, Tiarnan D. Keenan

    Purpose To report the natural history of untreated neovascular age-related macular degeneration (NV), concerning risk of subsequent macular atrophy. Design Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. Participants Age-Related Eye Disease Study (AREDS) participants, aged 55-80 years, who developed NV during follow-up (1992-2005), prior to the advent of anti-VEGF therapy. Methods Stereoscopic color fundus photographs were collected at annual study visits and graded centrally for features of late AMD. Incident macular atrophy after NV was examined by Kaplan-Meier analysis and proportional hazards regression. Main outcome measures Incident macular atrophy following NV, including risk of central involvement. Results Of the 4,757 AREDS participants, 708 eyes (627 participants) developed NV during follow-up and were eligible for analysis. The cumulative risks of incident macular atrophy after untreated NV were 9.6% (standard error 1.2%), 31.4% (2.2%), 43.1% (2.6%), and 61.5% (4.3%) at two, five, seven, and 10 years, respectively. This corresponded to a linear risk of 6.5%/year. The cumulative risk of central involvement was 30.4% (3.2%), 43.4% (3.8%), and 57.0% (4.8%) at first appearance of atrophy, two years, and five years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy after NV (HR 1.70, 1.17-2.49; p=0.006). However, higher 52-SNP AMD Genetic Risk Score was not associated with increased risk of macular atrophy after NV (hazard ratio 1.03, 95% CI 0.90-1.17; p=0.67). Similarly, no significant differences were observed according to the SNPs CFH rs1061170, CFH rs10922109, ARMS2 rs10490924, or C3 rs2230199. Conclusions The rate of incident macular atrophy following untreated NV is relatively high, increasing linearly over time and affecting half of eyes by eight years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated NV suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, though a contribution remains possible. Central involvement by macular atrophy is present in approximately one third of eyes at the time atrophy develops (similar to pure GA) and increases linearly to half of eyes at three years.

    更新日期:2019-11-27
  • Real-World Outcomes of Selective Laser Trabeculoplasty in the UK
    Ophthalmology (IF 7.732) Pub Date : 2019-11-26
    Anthony P. Khawaja, Joanna H. Campbell, Nicholas Kirby, Hitesh S. Chandwani, Ian Keyzor, Mousam Parekh, Andrew I. McNaught

    Objective Selective laser trabeculoplasty (SLT) is a common treatment option for managing glaucoma and ocular hypertension. We assessed the real-world effectiveness of SLT and baseline factors associated with treatment success in the United Kingdom (UK). Design Retrospective observational study of de-identified electronic medical records (Medisoft® Glaucoma module) from 5 UK ophthalmology teaching centers. Participants Adult patients undergoing their first recorded SLT. For bilateral SLT (same day), analyses included one randomly selected eye. Methods Patient demographics, procedure details and clinical outcomes data were extracted. Factors associated with treatment success were assessed using multivariable Cox regression. Main outcome measures Change from baseline in intraocular pressure (IOP) and glaucoma medication use at 12−18 and 24−36 months post-SLT. A Kaplan-Meier survival analysis was also conducted. SLT failure was defined as any further glaucoma procedure post-SLT or any of the following at 2 consecutive visits: IOP >21 mmHg, IOP reduction <20% from baseline, or an increase in glaucoma medications from baseline. Results 831 SLT-treated eyes (mean baseline IOP 22.0 mmHg) of 831 patients were analyzed. At 12−18 and 24−36 months post-SLT, respectively, significant reductions in IOP (−4.2 [95% CI: −4.7 to −3.7] and −3.4 [95% CI: −4.1 to −2.7] mmHg; both P<0.0001) and significant increases in the number of glaucoma medications (0.13 [95% CI: 0.04 to 0.23], P=0.007, and 0.20 [95% CI 0.06 to 0.33], P=0.005) were observed. Survival analysis demonstrated treatment success in 70%, 45%, and 27% of eyes at 6, 12, and 24 months post-SLT, respectively. Higher baseline IOP was strongly associated with treatment success (HR 0.64 for baseline IOP >21 mmHg vs ≤21 mmHg, 95% CI: 0.53–0.76; P<0.001). SLT success was not significantly associated with age (P=0.78), baseline visual field mean deviation (P=1.00) or the concurrent use of IOP-lowering medication (P=0.52). Conclusion Most patients initially responded to SLT, but a majority failed within 1 year. SLT efficacy was better in patients with higher baseline IOP but did not differ by glaucoma severity or by concurrent use of IOP-lowering medication. These findings may help inform which patients are suitable for SLT therapy.

    更新日期:2019-11-27
  • Ranibizumab or Aflibercept for Diabetic Macular Edema: Comparison of One-Year Outcomes from the Fight Retinal Blindness! Registry
    Ophthalmology (IF 7.732) Pub Date : 2019-11-26
    Sanjeeb Bhandari, Vuong Nguyen, Samantha Fraser-Bell, Hemal Mehta, Francesco Viola, Florian Baudin, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Mark Gillies, Daniel Barthelmes

    Purpose Both ranibizumab and aflibercept improved vision and decreased macular thickness in eyes with diabetic macular edema (DME) in clinical trials. This study compares the 12 month treatment outcomes of each drug in routine clinical practice. Design Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! Project. Participants Treatment-naïve eyes starting intravitreal injections of either ranibizumab (0.5mg) or aflibercept (2mg) for DME from 1 December 2013 to 1 June 2018 that were tracked in the registry. Methods Visual acuity (VA) was analyzed at 12 months in all eyes (completers, non-completers and eyes that switched treatment). Main Outcome measures The primary outcome was the mean change in VA (number of letters read on a logarithm of the minimum angle of resolution chart) from baseline to 12 months. Results We identified 383 eyes (Ranibizumab – 166, Aflibercept – 217) of 291 patients. Eyes of patients in the aflibercept group had a lower mean VA (mean difference [MD] -3.1 letters) and a thicker maculae (MD +26μm) than those of ranibizumab at baseline which was not significantly different. Patients on ranibizumab were older (MD +2.7 years). The adjusted MD in VA change and central subfield thickness (CST) reduction were +1 letter (1.4 for aflibercept versus 0.4 for ranibizumab, p = 0.4) and -30 microns (-85 versus -55, p<0.01) in eyes with initial VA ≥ 20/40 and +3 letters (10.6 versus 7.6, p<0.01) and -46 microns (-148 versus -102, p<0.02) in those presenting with VA ≤ 20/50. Eyes in the aflibercept group received more injections over 12 months, median (Q1, Q3) of 8 (6, 9), than the ranibizumab group, 6 (4, 8), though this difference was not significant (p = 0.13). Treatment switches, albeit low, were more frequent from ranibizumab to aflibercept than vice versa. Significantly more eyes in the aflibercept group were lost to follow-up within 12 months (21% versus 9% ranibizumab, P<0.01). Conclusions Both drugs were beneficial for DME. Aflibercept-treated eyes, which had borderline worse vision and thicker maculae at baseline, had larger reductions in CST after 12 months of treatment. Larger gains in VA was observed with aflibercept treatment when the initial VA was ≤ 20/50.

    更新日期:2019-11-27
  • Upper Cranial Nerve Involvement and IgG4-Related Optic Neuropathy
    Ophthalmology (IF 7.732) Pub Date : 2019-11-26
    Kenneth K.H. Lai, Regine Y.C. Chan, Joyce K.Y. Chin, Kenneth K.W. Li, Alvin L. Young, Hunter K.L. Yuen, Simon T.C. Ko, Kelvin K.L. Chong

    5% of one of the largest biopsy-proven IgG4ROD cohort suffered from IgG4-related optic neuropathy, which was associated with upper cranial nerve(s) involvement and retrobulbar mass. Visual prognosis was related to the level of presenting vision. (35 words)

    更新日期:2019-11-26
  • Demographics of a Large International Population of Patients Affected by Leber’s Hereditary Optic Neuropathy
    Ophthalmology (IF 7.732) Pub Date : 2019-11-25
    Lissa Poincenot, Alexander L. Pearson, Rustum Karanjia

    Objective The goal of this project was to study the demographics of Leber’s hereditary optic neuropathy (LHON) using a large international database of people affected by LHON. Design This was a cross-sectional study. Participants 1,517 people affected by LHON with a known pathogenic genetic mutation were included. Methods Self-reported genetic and demographic data was collected. The data was de-identified and then analyzed. Main Outcome Measures LHON mutation, gender, age of vision loss onset, geographical region. Results The data shows that both females and males can have symptom onset at any age. We found a 3:1 male:female ratio. Interestingly, below the age of 5 and after the age of 45, the male:female ratio of those becoming affected was approximately 1:1. A dramatic peak in age of onset of vision loss was found among males between ages 14-26. Disease onset in females occurred across all age groups, without any comparable dramatic peak of onset age. This study found that 10% of individuals become affected with LHON after the age of 50. As per the literature, we found that the m.11778, m.14484 and m.3460 mutations were the most common LHON point mutations in both males and females, with a similar age of onset distribution. Conclusions This is the largest study of LHON demographics to date. It shows that women carrying a LHON mutation are at higher risk of losing vision than is generally expected. Unlike the traditional 5:1 male:female ratio commonly reported in the literature, we found a 3:1 male:female ratio. Earlier studies may have had an ascertainment bias of overemphasizing the confirmation of this being a disease of young men. However, our data suggests LHON is a disease that affects both females and males of all ages. This should prompt physicians to conduct genetic testing for LHON in all patients who meet the clinical criteria, regardless of whether they fit the demographics traditionally associated with the disease. Counseling about LHON should be offered to all maternal bloodline relatives, females and males of all ages, as they are at risk of sudden-onset legal blindness.

    更新日期:2019-11-26
  • Anti-Vascular Endothelial Growth Factor Use and Atrophy in Neovascular Age-Related Macular Degeneration: Systematic Literature Review and Expert Opinion
    Ophthalmology (IF 7.732) Pub Date : 2019-11-22
    SriniVas R. Sadda, Robyn Guymer, Jordi M. Monés, Adnan Tufail, Glenn J. Jaffe

    Topic The objective was to summarize the rates of atrophy, risk factors and atrophy- associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (VEGF) treatment for macular neovascularization (MNV). Clinical relevance Age-related macular degeneration is a leading cause of vision loss worldwide and VEGF inhibitors are the primary treatment for nAMD. However, atrophy is frequently observed in eyes treated with anti-VEGF therapy, prompting questions regarding a causative role for these therapies in atrophy development. Methods PubMed was searched for articles published in the past 5 years (January 1, 2014, to January 10, 2019). Studies including atrophy outcome(s) in patients with AMD who received anti-VEGF treatment were included. Review articles, retrospective studies, case reports/studies, preclinical studies, prevalence data reports, and non-English studies were excluded. Randomization was not required. Results Overall, 145 studies were identified; 29 publications were included, with cohorts ranging from 8 to 1185 eyes. Imaging modalities used to assess atrophy varied across studies. All studies confirmed the occurrence of atrophy and, when available, longitudinal data from the included studies demonstrated an increase in atrophy incidence over time. Key risk factors or phenotypes associated with atrophy were fellow eye atrophy, reticular pseudodrusen, increased injections, and Type 3 lesion. In addition, visual acuity loss was noted with foveal atrophy. Conclusion All studies demonstrated that atrophy occurs in the context of MNV treated with anti-VEGF therapy; however, it is not clear whether anti-VEGF treatment is causative of atrophy vs associated with atrophy development. The included studies were not designed or powered to assess atrophy as a primary outcome. In addition, it is difficult to determine whether prognostic factors directly affect atrophy. Furthermore, patient populations in clinical trials do not necessarily represent real-world patients. Although phenotypes and risk factors may help to identify those at greater risk of developing atrophy, it is important to recognize that adequately treating exudative MNV remains the best option to optimize vision outcomes in patients with nAMD, particularly given the risk of vision loss with undertreatment observed in the real world.

    更新日期:2019-11-22
  • Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media
    Ophthalmology (IF 7.732) Pub Date : 2019-11-21
    Allister Gibbons, Ella H. Leung, Sonia H. Yoo

    Objective To evaluate the cost-effectiveness of supplementing hypothermic corneal storage media (CSM) with antifungal therapy Design Cost-effectiveness analysis (CEA) Subject Base case of a Fuch’s endothelial dystrophy patient undergoing a first eye keratoplasty Methods Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasties (EK) and penetrating keratoplasties (PKP); amphotericin B, voriconazole, caspofungin, and combination therapy, and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 U.S. dollars. Main Outcome Measures Incremental cost-effectiveness ratios (ICERs) Results In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20,000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of post keratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKPs, antifungal supplementation was less cost-effective than for EKs. Conclusions Antifungal supplementation with amphotericin B for endothelial keratoplasty grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

    更新日期:2019-11-22
  • Contribution of Genome-Wide Significant Single Nucleotide Polymorphisms in Myopia Prediction
    Ophthalmology (IF 7.732) Pub Date : 2019-07-02
    Yanxian Chen, Xiaotong Han, Xiaobo Guo, Yonghui Li, Jonathan Lee, Mingguang He

    Purpose To determine the added predictive ability of genome-wide significant single nucleotide polymorphisms (SNPs) in refraction prediction in children and investigate the earliest age threshold for an accurate prediction of high myopia. Design Prospective longitudinal study. Participants A total of 1063 first-born twins followed annually between 2006 and 2015 in China. The exposures were genetic factors (parental myopia, SNPs) and environmental factors (near work, outdoor activity). Methods Five linear mixed-effect models, consisting of different combinations of age, gender, genetic, and environmental factors, were built to predict myopia development. All predictions were performed on the basis of spherical equivalent (SE) at baseline and the measurements on the second and third visits. Main Outcome Measures The primary outcome measure was SE at the last visit among all subjects, and the secondary outcome measure was the presence of high myopia at the age of 18 years. Results Mean age of the study population was 10.5±2.2 years (range, 7–15 years) at baseline, and 48.6% were male. In linear mixed-effect models, age, age square, gender, paternal SE, maternal SE, and genetic risk scores (GRSs) showed a significant fixed effect, whereas outdoor and near-work time were not significant to SE at the last visit. Incorporating more follow-up data into the model showed better performance across all models. In the prediction of the presence of high myopia at 18 years of age, the model consisting of only age and gender showed a good performance (area under the curve [AUC] = 0.95), whereas the addition of SNPs did not enhance the model performance significantly. The AUC for predicting high myopia was >0.95 after the age of 13 years for participants with a single visit and after the age of 12 years for those with 1 more visit data. Conclusions A simple model incorporating age, sex, and relevant refraction data is sufficient to accurately predict high myopia; there was limited improvement in the prediction model after adding genetic information. Furthermore, this prediction on the outcome at 18 years is possible when the child is aged 12 to 13 years.

    更新日期:2019-11-20
  • The Increasing Burden of Myopia in Israel among Young Adults over a Generation
    Ophthalmology (IF 7.732) Pub Date : 2019-06-29
    Yinon Shapira, Michael Mimouni, Yossy Machluf, Yoram Chaiter, Haitam Saab, Eedy Mezer

    Purpose To determine the trends in prevalence of myopia in Israeli young adults over approximately a generation, as well as associated factors and variation in the impact of these factors on myopia prevalence in this region over time. Design Retrospective, cross-sectional study. Participants One hundred four thousand six hundred eighty-nine consecutive persons 16 to 19 years of age born between 1971 and 1994 who had not yet enlisted in the Israeli Army but had completed the medical profiling process. Methods Using data collected at a north Israel recruitment center, the prevalence of myopia over time was estimated, and a polynomial regression analysis was performed to assess significance of nonlinear trends. Associations of demographic and socioeconomic factors with myopia were assessed, and trends over time were analyzed using a factorial logistic regression. Main Outcome Measures The primary outcome measure was factors associated with the prevalence of myopia over time. The secondary outcome measure was a description of the change in prevalence of myopia over time. Results The prevalence of myopia increased 1.284-fold over 24 years from 20.4% among participants born between 1971 and 1982 to 26.2% among participants born between 1983 and 1994. A quite similar increase was observed among males (from 17.9% to 22.7%, respectively) and females (from 23.9% to 30.8%, respectively). The factors found to be associated with myopia were as follows: more recent date of birth, female gender, more years of education, being the eldest child, non-Israeli ethnic origin, and urban residence. However, there were significant trends over time in the effects of some of these factors, most notably an attenuation of the difference between participants of different religions in the recent birth-years period. Most of these associations and trends were observed in both males and females separately, with some gender-specific variations. Immigrants from Ethiopia who were raised in Israel were highly more likely to demonstrate myopia than those who arrived at an older age. Conclusions This study demonstrated an increase in the prevalence of myopia and the possible associations of urbanization- and higher education-related factors among several subpopulations and the risk for myopia developing.

    更新日期:2019-11-20
  • The Association of Aspirin Use with Age-Related Macular Degeneration Progression in the Age-Related Eye Disease Studies
    Ophthalmology (IF 7.732) Pub Date : 2019-06-26
    Tiarnan D. Keenan, Henry E. Wiley, Elvira Agrón, Mary E. Aronow, William G. Christen, Traci E. Clemons, Emily Y. Chew

    Purpose To analyze the potential association between aspirin use and progression of age-related macular degeneration (AMD). Design Two prospective cohort studies within 2 controlled clinical trials of oral supplementation for age-related eye disease. Participants Age-Related Eye Disease Study (AREDS) participants 55 to 80 years of age and AREDS2 participants 50 to 85 years of age. Methods Propensity scores for aspirin use were calculated for AREDS and AREDS2 participants separately by logistic regression. Of the participants without late AMD (geographic atrophy [GA] or neovascular AMD) in either eye at study baseline, aspirin users were matched 1:1 with nonusers by propensity score (separately for AREDS and AREDS2). Proportional hazards regression was performed, adjusting for age, on the matched participants to evaluate associations between aspirin propensity score and progression to late AMD (and its subtypes). Main Outcome Measures Progression to late AMD on color fundus photographs, graded centrally. Results Of the 3734 eligible AREDS participants, 1049 (28.1%) were taking aspirin, and of the 2403 eligible AREDS2 participants, 1198 (49.9%) were taking aspirin. After matching by propensity score, the characteristics of the users and nonusers were similar in both studies. Of the 1950 matched AREDS participants and 1694 matched AREDS2 participants, over a median follow-up of 10.1 years and 5.0 years, respectively, the numbers who progressed to late AMD, GA, or neovascular AMD were 454 (23.3%), 345 (17.7%), and 278 (14.3%), respectively, in AREDS and 643 (38.0%), 402 (24.6%), and 341 (20.1%) in AREDS2. The hazard ratios of progression in quintile 5 (highest propensity for aspirin use) versus 1 (reference) were 1.17 (P = 0.35), 1.24 (0.25), and 0.95 (0.81), respectively, in AREDS and 1.26 (0.09), 1.46 (0.03), and 1.12 (0.58) in AREDS2. No significant association with progression to late AMD was observed for quintiles 2 through 5 for any of the 3 outcomes in either study. Conclusions Aspirin use was not associated significantly with progression to late AMD or its subtypes in either the AREDS or AREDS2. Patients with AMD need not avoid aspirin for this reason when its use is medically indicated.

    更新日期:2019-11-20
  • Prevalence, Risk, and Genetic Association of Reticular Pseudodrusen in Age-related Macular Degeneration
    Ophthalmology (IF 7.732) Pub Date : 2019-07-29
    Amitha Domalpally, Elvira Agrón, Jeong W. Pak, Tiarnan D. Keenan, Fredrick L. Ferris, Traci E. Clemons, Emily Y. Chew

    Purpose To determine the prevalence of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD), assess the role of RPD as an independent risk factor for late AMD development, and evaluate genetic association with RPD. Design Prospective cohort study. Participants Participants with intermediate AMD in 1 or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplement. Methods Fundus autofluorescence (FAF) images from a subset of AREDS2 participants were evaluated at annual visits for presence of RPD. Six single nucleotide polymorphisms—rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A)—and the genetic risk score (GRS) were assessed for association with RPD. Development of late AMD, defined as geographic atrophy (GA) or neovascular AMD (NVAMD), was identified. Main Outcome Measures Prevalence of RPD, odds ratio (OR) of late AMD development, and genetic associations of RPD. Results The FAF images were evaluated for 5021 eyes (2516 participants). Reticular pseudodrusen were seen in 1186 eyes (24% of eyes, 29% of participants). Prevalence of RPD varied with baseline AREDS AMD severity level: 6% in early AMD (n = 458), 26% in intermediate AMD (n = 2606), 36% in GA (n = 682), and 19% in NVAMD (n = 1246). Mean age of participants with RPD was 79 years (standard deviation [SD], 7) and 75 years (SD, 8) in those without RPD (P < 0.0001). Reticular pseudodrusen were more frequent in female participants (65% RPD vs. 53% no RPD). Odds ratio adjusted for baseline age, gender, race, educational status, smoking, and AMD severity level for 1710 eyes at risk of developing late AMD at the next annual visit was 2.42 (95% confidence interval [CI], 1.80–3.24; P < 0.001) for GA and 1.21 (95% CI, 0.87–1.7; P = 0.26) for NVAMD. Presence of RPD was significantly associated with higher GRS (P < 0.0001) and ARMS2 risk alleles (P < 0.0001) and, at a nominal level, with C3 risk alleles (P = 0.04) and CFH risk alleles (P = 0.048 for homozygotes). Conclusions Participants with RPD have an increased risk of progression to GA but not NVAMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis.

    更新日期:2019-11-20
  • OCT Angiography Metrics Predict Progression of Diabetic Retinopathy and Development of Diabetic Macular Edema
    Ophthalmology (IF 7.732) Pub Date : 2019-06-26
    Zihan Sun, Fangyao Tang, Raymond Wong, Jerry Lok, Simon K.H. Szeto, Jason C.K. Chan, Carmen K.M. Chan, Clement C. Tham, Danny S. Ng, Carol Y. Cheung

    Purpose To prospectively determine the relationship of OCT angiography (OCTA) metrics to diabetic retinopathy (DR) progression and development of diabetic macular edema (DME). Design Prospective, observational study. Participants A total of 205 eyes from 129 patients with diabetes mellitus followed up for at least 2 years. Methods All participants underwent OCTA with a swept-source OCT device (DRI-OCT Triton, Topcon, Inc, Tokyo, Japan). Individual OCTA images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were generated by IMAGEnet6 (Basic License 10). After a quality check, automated measurements of foveal avascular zone (FAZ) area, FAZ circularity, vessel density (VD), and fractal dimension (FD) of both SCP and DCP were then obtained. Main Outcome Measures Progression of DR and development of DME. Results Over a median follow-up of 27.14 months (interquartile range, 24.16–30.41 months), 28 of the 205 eyes (13.66%) developed DR progression. Of the 194 eyes without DME at baseline, 17 (8.76%) developed DME. Larger FAZ area (hazard ratio [HR], 1.829 per SD increase; 95% confidence interval [CI], 1.332–2.512), lower VD (HR, 1.908 per SD decrease; 95% CI, 1.303–2.793), and lower FD (HR, 4.464 per SD decrease; 95% CI, 1.337–14.903) of DCP were significantly associated with DR progression after adjusting for established risk factors (DR severity, glycated hemoglobin, duration of diabetes, age, and mean arterial blood pressure at baseline). Lower VD of SCP (HR, 1.789 per SD decrease; 95% CI, 1.027–4.512) was associated with DME development. Compared with the model with established risk factors alone, the addition of OCTA metrics improved the predictive discrimination of DR progression (FAZ area of DCP, C-statistics 0.723 vs. 0.677, P < 0.001; VD of DCP, C-statistics 0.727 vs. 0.677, P = 0.001; FD of DCP, C-statistics 0.738 vs. 0.677, P < 0.001) and DME development (VD of SCP, C-statistics 0.904 vs. 0.875, P = 0.036). Conclusions The FAZ area, VD, and FD of DCP predict DR progression, whereas VD of SCP predicts DME development. Our findings provide evidence to support that OCTA metrics improve the evaluation of risk of DR progression and DME development beyond traditional risk factors.

    更新日期:2019-11-20
  • OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study
    Ophthalmology (IF 7.732) Pub Date : 2019-05-29
    Marco Nassisi, Jianqin Lei, Nizar Saleh Abdelfattah, Ayesha Karamat, Siva Balasubramanian, Wenying Fan, Akihito Uji, Kenneth M. Marion, Kirstie Baker, Xiwen Huang, Elizabeth Morgenthien, Srinivas R. Sadda

    Purpose To evaluate the relationship between OCT features and progression to late age related-macular degeneration (AMD) in the fellow eyes of patients enrolled in the Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular AMD (HARBOR) (ClinicalTrials.gov identifier, NCT00891735). Design Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. Participants Evaluable patients (n = 501) with macular neovascularization (MNV) secondary to neovascular AMD and early or intermediate AMD in the fellow eye. Methods Volume OCT scans from 501 fellow eyes of 501 patients with MNV were reviewed. Baseline OCT features that were assessed included intraretinal hypereflective foci (IHRF), hyporeflective foci (hRF) within drusenoid lesions (DLs), subretinal drusenoid deposits (SDDs), and drusen volume (DV) of 0.03 mm3 or more. OCT images obtained at months 6, 12, 18, and 24 were graded by masked graders for late AMD (defined as MNV, complete retinal pigment epithelium and photoreceptor atrophy [cRORA], or both). Participant demographic characteristics (age, gender, and smoke exposure) and baseline OCT features were correlated with progression to late AMD. Main Outcome Measures Incidence of late AMD, hazard ratio (HR) for demographics, and OCT risk factors. Results At month 24, 33.13% of eyes (166/501) demonstrated late AMD: 20.96% (105/501) demonstrated cRORA, whereas 12.18% (61/501) demonstrated MNV. Baseline demographic factors were not associated significantly with development of late AMD, whereas significant associations were identified for all OCT features. Intraretinal hypereflective foci had an HR of 5.21 (95% confidence interval [CI], 3.29–8.26), hRF within DLs had an HR of 2.42 (95% CI, 1.74–3.38), SDD had an HR of 1.95 (95% CI, 1.34–2.82), and DV of 0.03 mm3 or more had an HR of 1.46 (95% CI, 1.03–2.07). The correlation remained significant when considering only the progression to cRORA and MNV alone, except for DV, which was not associated significantly with progression to MNV. Conclusions We confirmed that 4 previously reported OCT risk factors were associated with progression to late AMD in the fellow eyes of patients newly diagnosed with MNV. Although outcomes of more than 2 years were not evaluated, these findings may help to identify high-risk AMD patients.

    更新日期:2019-11-20
  • Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti–Vascular Endothelial Growth Factor
    Ophthalmology (IF 7.732) Pub Date : 2019-06-26
    Aude Couturier, Pierre-Antoine Rey, Ali Erginay, Carlo Lavia, Sophie Bonnin, Bénédicte Dupas, Alain Gaudric, Ramin Tadayoni

    Purpose To assess change in retinal nonperfusion (NP) after anti–vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) using 2 different imaging modalities: swept-source widefield (SS-WF) OCT angiography (OCTA) and ultra-widefield (UWF) fluorescein angiography (FA). Design Observational case series. Participants Ten eyes of 9 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) initiating 3 monthly anti-VEGF intravitreal injections for DME. Methods All eyes were imaged with UWF color fundus photographs (CFPs), UWF FA, and SS-WF OCTA at baseline (M0) and 1 month after the third anti-VEGF injection (M3). All images were aligned and divided into 16 boxes for analysis of NP areas by 2 blinded retina specialists. Main Outcome Measures The number of discrepancies between SS-WF OCTA and UWF FA regarding the detection of NP areas and small vessels passing through NP areas; assessment of DR severity on UWF CFP; and change in each NP area between M0 and M3: number of boxes/eye with presence of at least 1 NP area, number of arterioles or venules that disappeared or reappeared, and number of NP areas in which capillaries disappeared or reappeared. Results The diabetic retinopathy (DR) severity score improved by at least 1 stage in 8 of 10 eyes, with a significant decrease in the mean number of microaneurysms and retinal hemorrhages on UWF CFP at M3 versus M0 (n = 40±28 vs. 121±57; P = 0.0020) and regression of fundus neovascularization when present. All NP areas detected on FA were seen on SS-WF OCTA, but additional NP areas were detected on SS-WF OCTA at M0 in 29% (46/160) of boxes. No reperfusion of arterioles or venules was observed at M3 on FA or SS-WF OCTA. Retinal capillaries were only visible on OCTA, and no reperfusion in NP areas was observed even when a reduction in dark areas was visible on FA. Conclusions No reperfusion of vessels or capillary network was detected in NP areas using 2 imaging techniques, UWF FA and SS-WF OCTA, in eyes with DR after 3 anti-VEGF injections. The detection rate of NP areas was higher with SS-WF OCTA than with UWF FA.

    更新日期:2019-11-20
  • Different Factors Associated with 2-Year Outcomes in Patients with Branch versus Central Retinal Vein Occlusion Treated with Ranibizumab
    Ophthalmology (IF 7.732) Pub Date : 2019-07-23
    Raafay Sophie, Pin-wen Wang, Roomasa Channa, Carlos Quezada-Ruiz, Ann Clark, Peter A. Campochiaro

    Purpose To investigate characteristics associated with visual and anatomic outcomes in branch and central retinal vein occlusion (BRVO and CRVO) patients treated with ranibizumab. Design Post hoc analysis of patients with BRVO and CRVO from 2 multicenter clinical trials who completed month 12 of the HORIZON extension trial. Participants 205 patients with BRVO and 181 patients with CRVO who completed month 12 of the extension trial. Methods With the use of logistic regression, covariates with a P value < 0.20 from univariate analysis were included in multivariate models to identify independent factors associated with a given outcome (at P < 0.05), with preset variables of disease duration and original treatment assignment. Main Outcome Measures Best-corrected visual acuity (BCVA) ≥20/40 (≥70 letters), gain ≥15 letters, and central subfield thickness (CST) ≤250 μm at HORIZON month 12. Results In patients with BRVO, good baseline BCVA (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.30–1.79), male sex (OR, 2.48; 95% CI, 1.20–5.13), and normal hematocrit (low vs. normal, OR, 0.26; 95% CI, 0.12–0.59) predicted BCVA ≥20/40; high central foveal thickness (OR, 1.03; 95% CI, 1.01–1.04) and normal hematocrit (low vs. normal, OR, 0.31; 95% CI, 0.15–0.66) predicted BCVA improvement ≥15 letters; and extensive baseline subretinal fluid modestly predicted CST ≤250 μm (OR, 1.08; 95% CI, 1.00–1.16). In patients with CRVO, good baseline BCVA (OR, 1.59; 95% CI, 1.35–1.89), never smoking (OR, 2.80; 95% CI, 1.27–6.17), and young age (OR, 0.58; 95% CI, 0.41–0.82) predicted BCVA ≥20/40; never smoking (OR, 2.13; 95% CI, 1.03–4.39), young age (OR, 0.41; 95% CI, 0.28–0.59), poor baseline BCVA (OR, 0.82; 95% CI, 0.73–0.93), hypertension (OR, 4.47; 95% CI, 1.70–11.75), and low diastolic ocular perfusion pressure (OPP) throughout the study (OR, 0.39; 95% CI, 0.21–0.72) predicted BCVA improvement ≥15 letters; and young age (OR, 0.65; 95% CI, 0.47–0.90), lower mean hematocrit (low vs. normal, OR, 2.81; 95% CI, 1.06–7.49), high systolic OPP throughout the study (OR, 1.61; 95% CI, 1.14–2.27), large areas of central hemorrhage (OR, 1.44; 95% CI, 1.04–2.00), and no subretinal fluid (OR, 2.15; 95% CI, 1.06–4.40) predicted CST ≤250 μm. Conclusions There are substantial differences in good outcome factors in CRVO versus BRVO, suggesting differences in pathophysiology. Young age, never smoking, hemodilution, and hypertension/high systolic perfusion pressure are more beneficial in CRVO, suggesting that avoidance of sluggish blood flow and maintenance of perfusion may be particularly important in CRVO.

    更新日期:2019-11-20
  • Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography
    Ophthalmology (IF 7.732) Pub Date : 2019-07-15
    S. Tammy Hsu, Hoan T. Ngo, Sandra S. Stinnett, Nathan L. Cheung, Robert J. House, Michael P. Kelly, Xi Chen, Laura B. Enyedi, S. Grace Prakalapakorn, Miguel A. Materin, Mays A. El-Dairi, Glenn J. Jaffe, Sharon F. Freedman, Cynthia A. Toth, Lejla Vajzovic

    Purpose To assess macular vasculature in healthy infants and children using OCT angiography (OCTA). Design Prospective cross-sectional study. Participants One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks–17 years) treated at the Duke University Eye Center. Methods We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes. Main Outcome Measures The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC. Results The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm2; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00). Conclusions Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.

    更新日期:2019-11-20
  • Highly Variable Disease Courses in Siblings with Stargardt Disease
    Ophthalmology (IF 7.732) Pub Date : 2019-07-16
    Dyon Valkenburg, Esmee H. Runhart, Nathalie M. Bax, Bart Liefers, Stanley L. Lambertus, Clara I. Sánchez, Frans P.M. Cremers, Carel B. Hoyng

    Purpose To investigate intersibling phenotypic concordance in Stargardt disease (STGD1). Design Retrospective cohort study. Participants Siblings with genetically confirmed STGD1 and at least 1 available fundus autofluorescence (FAF) image of both eyes. Methods We compared age at onset within families. Disease duration was matched to investigate differences in best-corrected visual acuity (BCVA) and compared the survival time for reaching severe visual impairment (<20/200 Snellen or >1.0 logarithm of the minimum angle of resolution [logMAR]). Central retinal atrophy area was quantified independently by 2 experienced graders using semiautomated software and compared between siblings. Both graders performed qualitative assessment of FAF and spectral-domain (SD) OCT images to identify phenotypic differences. Main Outcome Measures Differences in age at onset, disease duration-matched BCVA, time to severe visual impairment development, FAF atrophy area, FAF patterns, and genotypes. Results Substantial differences in age at onset were present in 5 of 17 families, ranging from 13 to 39 years. Median BCVA at baseline was 0.60 logMAR (range, –0.20 to 2.30 logMAR; Snellen equivalent, 20/80 [range, 20/12–hand movements]) in the right eye and 0.50 logMAR (range, –0.20 to 2.30 logMAR; Snellen equivalent, 20/63 [range, 20/12–hand movements]) in the left eye. Disease duration-matched BCVA was investigated in 12 of 17 families, and the median difference was 0.41 logMAR (range, 0.00–1.10 logMAR) for the right eye and 0.41 logMAR (range, 0.00–1.08 logMAR) for the left eye. We observed notable differences in time to severe visual impairment development in 7 families, ranging from 1 to 29 years. Median central retinal atrophy area was 11.38 mm2 in the right eye (range, 1.98–44.78 mm2) and 10.59 mm2 in the left eye (range, 1.61–40.59 mm2) and highly comparable between siblings. Similarly, qualitative FAF and SD OCT phenotypes were highly comparable between siblings. Conclusions Phenotypic discordance between siblings with STGD1 carrying the same ABCA4 variants is a prevalent phenomenon. Although the FAF phenotypes are highly comparable between siblings, functional outcomes differ substantially. This complicates both sibling-based prognosis and genotype-phenotype correlations and has important implications for patient care and management.

    更新日期:2019-11-20
  • Visual Acuity Outcomes after Cataract Surgery
    Ophthalmology (IF 7.732) Pub Date : 2019-04-09
    Jacob T. Cox, Ganesh-Babu B. Subburaman, Beatriz Munoz, David S. Friedman, Ravilla D. Ravindran

    Purpose The primary objective was to assess associations between annual surgeon case volume and visual acuity outcomes after cataract surgery. Secondary objectives included (1) assessing associations between other case and patient characteristics and visual acuity outcomes and (2) assessing associations between annual surgeon case volume and complication rates. Design Database study. Participants All adult eyes that underwent small-incision cataract surgery (SICS) or phacoemulsification cataract extraction (PECE) with intraocular lens placement at the Aravind Eye Hospital, Madurai, India, during 2015. Methods Descriptive statistics were used to characterize the study population. Uncorrected visual acuity (UCVA) at follow-up was assessed relative to annual surgeon case volume and other case and demographic factors using bivariate linear regression with random effects modeling. Factors with P values of less than 0.20 on bivariate regression were included in multivariate linear regression with random effects modeling. Main Outcome Measures Postoperative UCVA after cataract surgery. Results Of 91 084 surgeries, 35 880 eyes were included in this study. Cases were performed by 69 surgeons, who varied in annual case volume from 76 to 2900 cases during the study period. Increasing annual surgeon case volume was independently associated with a statistically significant but clinically modest improvement in UCVA in PECE but not in SICS. This association was most pronounced when comparing surgeons with case volumes of 350 PECE/year or fewer; surgeons with more than 350 PECE/year had similar results to one another. Similarly, increased annual case volume was associated with significantly lower complication rates, both in PECE and SICS. Younger patient age was independently associated with improved visual acuity outcomes and lower complication rates in both PECE and SICS. Greater surgeon experience was associated with lower complication rates in PECE, but not SICS, and there was no significant association with visual acuity outcomes. Conclusions High-volume cataract surgeons showed improved visual acuity outcomes in PECE and lower complication rates in PECE and SICS. These findings further support the benefit of high-output ophthalmology clinics wherein individual surgeons perform a high number of cataract extractions annually, particularly in developing nations where there is a large backlog of untreated cataracts and the cataract patient-to-surgeon ratio is high.

    更新日期:2019-11-18
  • Associations with Corneal Hysteresis in a Population Cohort
    Ophthalmology (IF 7.732) Pub Date : 2019-07-05
    Bing Zhang, Yusrah Shweikh, Anthony P. Khawaja, John Gallacher, Sarah Bauermeister, Paul J. Foster

    Purpose To describe the distribution of corneal hysteresis (CH) in a large cohort and explore its associated factors and possible clinical applications. Design Cross-sectional study within the UK Biobank, a large cohort study in the United Kingdom. Participants We analyzed CH data from 93 345 eligible participants in the UK Biobank cohort, aged 40 to 69 years. Methods All analyses were performed using left eye data. Linear regression models were used to evaluate associations between CH and demographic, lifestyle, ocular, and systemic variables. Piecewise logistic regression models were used to explore the relationship between self-reported glaucoma and CH. Main Outcome Measures Corneal hysteresis (mmHg). Results The mean CH was 10.6 mmHg (10.4 mmHg in male and 10.8 mmHg in female participants). After adjusting for covariables, CH was significantly negatively associated with male sex, age, black ethnicity, self-reported glaucoma, diastolic blood pressure, and height. Corneal hysteresis was significantly positively associated with smoking, hyperopia, diabetes, systemic lupus erythematosus (SLE), greater deprivation (Townsend index), and Goldmann-correlated intraocular pressure (IOPg). Self-reported glaucoma and CH were significantly associated when CH was less than 10.1 mmHg (odds ratio, 0.86; 95% confidence interval, 0.79–0.94 per mmHg CH increase) after adjusting for covariables. When CH exceeded 10.1 mmHg, there was no significant association between CH and self-reported glaucoma. Conclusions In our analyses, CH was significantly associated with factors including age, sex, and ethnicity, which should be taken into account when interpreting CH values. In our cohort, lower CH was significantly associated with a higher prevalence of self-reported glaucoma when CH was less than 10.1 mmHg. Corneal hysteresis may serve as a biomarker aiding glaucoma case detection.

    更新日期:2019-11-18
  • Characteristics Associated with Adherence to Annual Dilated Eye Examinations among US Patients with Diagnosed Diabetes
    Ophthalmology (IF 7.732) Pub Date : 2019-06-15
    Sarah E. Eppley, Steven L. Mansberger, Saras Ramanathan, Eugene A. Lowry

    Purpose To identify the characteristics that are associated with adherence to annual diabetic eye exams and patient awareness of retinopathy using a nationally representative sample from the United States. Design Cross-sectional, secondary analysis. Participants National Health and Nutrition Examination Survey (NHANES) participants from 2005 to 2016 aged 20 years and older with diabetes mellitus. Methods The NHANES collected surveys every 2 years from 2005 to 2016, which contained demographic information, clinical information, and time to last dilated eye exam. From 2005 to 2008, retinal photographs were taken of all participants older than 40 years of age. We used univariate and multivariable logistic regression to determine the demographic and clinical factors associated with adherence to annual diabetic eye examinations and those associated with correctly reporting their retinopathy status. Main Outcome Measure Factors associated with adherence defined as having an eye exam within the preceding 12 or 24 months. Results From 2005 to 2016, NHANES surveyed 4072 individuals who represent 20 million Americans aged 20 years and older with self-report of diabetes. By using the adherence definitions of 12 and 24 months, 63.4% and 78.7%, respectively, were adherent to diabetic eye examinations. The nonadherence rates of 36.6% and 21.3% for this national estimate did not change from 2005 to 2016 (P = 0.7, logistic regression). Insurance status, age, education, income, cholesterol levels, duration of diabetes, and self-reported retinopathy were all significantly associated with adherence with both definitions (all P < 0.05, logistic regression). Insurance status had the highest predictive value, with 76% of Americans on combination private-public insurance adherent compared with 36% of uninsured. Most Americans with retinopathy incorrectly denied having the diagnosis (2 727 144/3 896 093 or 70%). Conclusions Multiple variables were associated with nonadherence to eye exams, with insurance status having the strongest association. Adherence with annual eye exams has not improved over the past decade. The majority of patients with retinopathy are unaware of this diagnosis, including the majority of those with a dilated funduscopic examination in the past year. Further improvements in education and adherence may reduce the visual morbidity caused by diabetes.

    更新日期:2019-11-18
  • Assessment of Vitreous Structure and Visual Function after Neodymium:Yttrium–Aluminum–Garnet Laser Vitreolysis
    Ophthalmology (IF 7.732) Pub Date : 2019-06-22
    Justin H. Nguyen, Jeannie Nguyen-Cuu, Fei Yu, Kenneth M. Yee, Jonathan Mamou, Ronald H. Silverman, Jeffrey Ketterling, J. Sebag

    Purpose Neodymium:yttrium–aluminum–garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision. Design Retrospective, comparative study. Participants One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation. Methods The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision. Main Outcome Measures Results of NEI-VFQ-39, QUS, BCVA, and CSF. Results Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings. Conclusions As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

    更新日期:2019-11-18
  • SALT Trial: Steroids after Laser Trabeculoplasty
    Ophthalmology (IF 7.732) Pub Date : 2019-06-06
    Sylvia L. Groth, Eiyass Albeiruti, Mariana Nunez, Roman Fajardo, Lucie Sharpsten, Nils Loewen, Joel S. Schuman, Jeffrey L. Goldberg

    Purpose This study examined whether short-term use of topical nonsteroidal anti-inflammatory drug (NSAID) or steroid therapy affected the efficacy of selective laser trabeculoplasty (SLT). Design Double-masked, randomized, placebo-controlled, dual-center, multisurgeon trial. Participants Patients older than 18 years with intraocular pressure (IOP) of more than 18 mmHg for whom the clinician decided SLT was the appropriately indicated therapy were randomized to 1 of 3 groups in a ratio of 1:1:1 as follows: ketorolac 0.5%, prednisolone 1%, or saline tears. Methods After SLT, patients randomized into each group were instructed to use an unmarked drop 4 times daily starting the day of SLT and continuing for 4 additional days. The Kruskal-Wallis test and Wilcoxon rank-sum test were used for continuous variables when comparing 2 or 3 treatment groups, respectively. The Fisher exact test was used for categorical variables. Main Outcome Measures The primary outcome of this study was IOP at 12 weeks. Secondary outcome measures included IOP at 1 and 6 weeks, patient-reported pain, and detectable anterior chamber inflammation. Results Ninety-six eyes of 85 patients fit inclusion criteria and were enrolled between the 2 sites. The NSAID, steroid, and placebo groups were similar in baseline demographics and baseline IOP (mean, 23.3±3.9 mmHg; P = 0.57). There was no statistically significant difference in IOP decrease among groups at week 6. Both the NSAID and steroid groups showed a statistically significantly greater decrease in IOP at week 12 compared with the placebo group (mean, –6.2±3.1 mmHg, –5.2±2.7 mmHg, and –3±4.3 mmHg, respectively; P = 0.02 [analysis of variance] and P = 0.002 [t test] for NSAID vs. placebo groups; P = 0.02 for steroid vs. placebo groups). Conclusions Significantly better IOP reduction at 12 weeks was measured in eyes treated with steroid or NSAID drops after SLT. Short-term postoperative use of NSAID or steroid drops may improve IOP reduction after SLT. Longer-term follow-up studies are indicated.

    更新日期:2019-11-18
  • Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity
    Ophthalmology (IF 7.732) Pub Date : 2019-06-08
    Justis P. Ehlers, Alice C. Jiang, Joseph D. Boss, Ming Hu, Natalia Figueiredo, Amy Babiuch, Katherine Talcott, Sumit Sharma, Jenna Hach, Thuy Le, Alison Rogozinski, Leina Lunasco, Jamie L. Reese, Sunil K. Srivastava

    Purpose To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. Design Retrospective image analysis study. Methods Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. Main Outcome Measures Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. Results Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10–16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10–16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10–7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. Conclusions Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

    更新日期:2019-11-18
  • A Deep Learning Approach for Automated Detection of Geographic Atrophy from Color Fundus Photographs
    Ophthalmology (IF 7.732) Pub Date : 2019-06-11
    Tiarnan D. Keenan, Shazia Dharssi, Yifan Peng, Qingyu Chen, Elvira Agrón, Wai T. Wong, Zhiyong Lu, Emily Y. Chew

    Purpose To assess the utility of deep learning in the detection of geographic atrophy (GA) from color fundus photographs and to explore potential utility in detecting central GA (CGA). Design A deep learning model was developed to detect the presence of GA in color fundus photographs, and 2 additional models were developed to detect CGA in different scenarios. Participants A total of 59 812 color fundus photographs from longitudinal follow-up of 4582 participants in the Age-Related Eye Disease Study (AREDS) dataset. Gold standard labels were from human expert reading center graders using a standardized protocol. Methods A deep learning model was trained to use color fundus photographs to predict GA presence from a population of eyes with no AMD to advanced AMD. A second model was trained to predict CGA presence from the same population. A third model was trained to predict CGA presence from the subset of eyes with GA. For training and testing, 5-fold cross-validation was used. For comparison with human clinician performance, model performance was compared with that of 88 retinal specialists. Main Outcome Measures Area under the curve (AUC), accuracy, sensitivity, specificity, and precision. Results The deep learning models (GA detection, CGA detection from all eyes, and centrality detection from GA eyes) had AUCs of 0.933–0.976, 0.939–0.976, and 0.827–0.888, respectively. The GA detection model had accuracy, sensitivity, specificity, and precision of 0.965 (95% confidence interval [CI], 0.959–0.971), 0.692 (0.560–0.825), 0.978 (0.970–0.985), and 0.584 (0.491–0.676), respectively, compared with 0.975 (0.971–0.980), 0.588 (0.468–0.707), 0.982 (0.978–0.985), and 0.368 (0.230–0.505) for the retinal specialists. The CGA detection model had values of 0.966 (0.957–0.975), 0.763 (0.641–0.885), 0.971 (0.960–0.982), and 0.394 (0.341–0.448). The centrality detection model had values of 0.762 (0.725-0.799), 0.782 (0.618–0.945), 0.729 (0.543–0.916), and 0.799 (0.710–0.888). Conclusions A deep learning model demonstrated high accuracy for the automated detection of GA. The AUC was noninferior to that of human retinal specialists. Deep learning approaches may also be applied to the identification of CGA. The code and pretrained models are publicly available at https://github.com/ncbi-nlp/DeepSeeNet.

    更新日期:2019-11-18
  • No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2
    Ophthalmology (IF 7.732) Pub Date : 2019-06-12
    Freekje van Asten, Chi-Yang Chiu, Elvira Agrón, Traci E. Clemons, Rinki Ratnapriya, Anand Swaroop, Michael L. Klein, Ruzong Fan, Emily Y. Chew

    Purpose To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design Post hoc analysis of a randomized trial. Participants White AREDS2 participants. Methods AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene–supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. Main Outcome Measures The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10–5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

    更新日期:2019-11-18
  • Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa
    Ophthalmology (IF 7.732) Pub Date : 2019-05-01
    Feng-Juan Gao, Jian-Kang Li, Han Chen, Fang-Yuan Hu, Sheng-Hai Zhang, Yu-He Qi, Ping Xu, Dan-Dan Wang, Lu-Sheng Wang, Qing Chang, Yong-Jin Zhang, Wei Liu, Wei Li, Min Wang, Fang Chen, Ge-Zhi Xu, Ji-Hong Wu

    Purpose To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population. Design Cohort study. Participants A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 2701) were recruited. Methods All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation. Main Outcome Measures Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing. Results Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup (≤5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6–16 years old, 73.74%) and late-onset subgroup (≥17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP. Conclusions This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum is completely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to family members. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in China.

    更新日期:2019-11-18
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