Neil M Bressler

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (305)1388.67 Total impact

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    ABSTRACT: Importance: Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment. Objective: To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography. Design, setting, and participants: Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015. Interventions: Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. Main outcomes and measures: One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST. Results: In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (-8% to 35%) for aflibercept vs ranibizumab. Conclusions and relevance: These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients. Trial registration: Identifier: NCT01627249.
    Jama Ophthalmology 11/2015; DOI:10.1001/jamaophthalmol.2015.4599 · 3.32 Impact Factor
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    ABSTRACT: Importance: The potential effect of treatments for diabetic macular edema (DME) on driving should be of value to patients and clinicians, such as ophthalmologists and other physicians, who treat patients with diabetes mellitus. Objective: To determine the effect of ranibizumab on driving and patient-reported vision function relevant to driving among patients with DME. Design, setting, and participants: This exploratory post hoc analysis was conducted between October 1, 2011, and July 25, 2015, based on deidentified data from phase 3, multicenter, randomized clinical trials (RIDE, RISE, and RESTORE trials). Individuals assigned randomly to monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab in RIDE and RISE or to macular laser, macular laser plus 0.5-mg ranibizumab (3-monthly doses, then as needed), or 0.5-mg (3-monthly doses, then as needed) in RESTORE. Main outcomes and measures: Driving items from the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25) at baseline through 24 months in RIDE/RISE (pooled) and through 12 months in RESTORE. Results: A total of 71.2% of 753 patients in RIDE/RISE and 50.4% of 345 patients in RESTORE reported driving at baseline; at least 55% reported still driving at follow-up. Among those not driving at baseline in RIDE/RISE, at 12 months, 7.0% (95% CI, -5.0 to 19.0) more in the 0.3-mg group and 14.4% (95% CI, 1.1 to 27.7) more in the 0.5-mg group vs the sham group reported driving. Among those not driving at baseline in RESTORE, at 12 months, 4.2% (95% CI, -7.7 to 16.1) more in the laser plus 0.5-mg group and 0.9% (95% CI, -10.3 to 12.1) more in the 0.5-mg group vs the laser group reported driving. Although balanced at baseline across treatment groups for RESTORE and RIDE/RISE, the proportion of patients with best-corrected visual acuity typically required for an unrestricted license (20/40 or better in at least 1 eye) appeared greater at month 12 in the ranibizumab groups (77 of 80 [96.3%] for 0.5 mg + laser and 91 of 93 [97.8%] for 0.5 mg) vs laser (71 of 79 [89.9%]) in RESTORE, and at months 12 (112 of 123 [91.1%] and 136 of 137 [99.3%] in 0.3- and 0.5-mg groups, respectively) and 24 (113 of 123 [91.9%] and 135 of 137 [98.5%] in the 0.3- and 0.5-mg groups, respectively) vs sham (121 of 147 [82.3%] and 122 of 147 [83.0%]) in RIDE/RISE. Conclusions and relevance: These results suggest that 12 months after initiating ranibizumab for vision impairment from center-involved DME, patients not driving at initiation of treatment are more likely to report driving and have driving-eligible visual acuity of 20/40 or better in the better-seeing eye than those treated with sham or laser. Trial registration: Identifier: RESTORE: NCT00687804; RIDE: NCT00473382; and RISE: NCT00473330.
    Jama Ophthalmology 11/2015; DOI:10.1001/jamaophthalmol.2015.4636 · 3.32 Impact Factor
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    ABSTRACT: Importance: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). Objective: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. Design, setting, and participants: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Interventions: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. Main outcomes and measures: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. Results: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. Conclusions and relevance: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. Trial registration: Identifier: NCT01489189.
    JAMA The Journal of the American Medical Association 11/2015; 314(20):1-11. DOI:10.1001/jama.2015.15217 · 35.29 Impact Factor
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    ABSTRACT: Importance: The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. Objectives: To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. Evidence review: The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. Findings: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. Conclusions and relevance: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.
    Jama Ophthalmology 10/2015; DOI:10.1001/jamaophthalmol.2015.4110 · 3.32 Impact Factor
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    ABSTRACT: Importance: Patients with intermediate age-related macular degeneration (AMD) using a home monitoring device have less loss of visual acuity, on average, at detection of choroidal neovascularization than do individuals using standard care monitoring techniques. Understanding the frequency with which patients are likely to initiate using a home monitoring device successfully is important in planning implementation of the device into practice. Objectives: To determine the frequency with which patients with intermediate AMD qualify to use a home monitoring device and to establish a reliable baseline reference value with the device to monitor their AMD for progression to choroidal neovascularization. Design, setting, and participants: Between October 8, 2010, and May 20, 2011, a total of 131 eligible participants within a university-based retina practice with intermediate AMD in the study eye and visual acuity of 20/63 or better completed an in-clinic qualification test for the home device. Intermediate AMD was defined as multiple intermediate-sized drusen or at least 1 large druse. If both eyes were eligible, the eye with better visual acuity was selected as the study eye. If both eyes had the same visual acuity, the patient used the eye with subjectively better vision. Analysis was performed between August 1, 2011, and January 11, 2014. Main outcomes and measures: The proportion of patients with reliable qualification test results and a test score predictive of successful home use of a monitoring device for detecting neovascular AMD, and the proportion who established a baseline reference value at home. Results: A total of 129 participants (98.5%; 95% CI, 96.4%-99.9%) had reliable qualification test results; 91 participants (69.5%; 95% CI, 61.6%-77.4%) who completed this test attained a score that suggested they would be able to successfully use the home device. Among the 91 participants who could initiate home testing, 83 did so, including 80 participants (87.9%; 95% CI, 81.2%-94.6%) who established a baseline value that could be used as a reference for future monitoring. Younger participants were more likely to qualify for home testing (mean [SD] age, 73.1 [8.4] vs 81.1 [7.1] years; P < .001). Visual acuity at study enrollment did not appear to be associated with successful qualification (mean visual acuity for those who did and did not qualify was 20/28 and 20/31, respectively; P = .10). Conclusions and relevance: These data suggest that the in-office qualification test is a useful screening tool to identify patients who may benefit from the home device. In any given retina practice, our data suggest an estimated 61.6% to 77.4% of patients with intermediate AMD should be able to produce reliable initial test results in the office test using the home monitoring device and pass a qualification test to initiate home monitoring. Subsequently, 81.2% to 94.6% of patients should be able to establish a home baseline reference value for future monitoring.
    Jama Ophthalmology 10/2015; DOI:10.1001/jamaophthalmol.2015.3684 · 3.32 Impact Factor
  • Yu Tung Wang · Mongkol Tadarati · Hendrik P Scholl · Neil M Bressler ·
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    ABSTRACT: Purpose: To describe visual acuity changes associated with several cycles of accumulation, disappearance, and reaccumulation of vitelliform material in Best disease, with fundus photographs, fluorescein angiograms, and optical coherence tomography images documenting these stages. Methods: Case report with 70 months of follow-up using fundus photography, fluorescein angiography, and optical coherence tomography to image the retina. A non-Hispanic white 33-year-old man with Best disease (positive for a mutation in the BEST1 gene, namely p.Tyr167Cys:c.500A>G). Results: The patient had a history of choroidal neovascularization (CNV) followed by scarring of the macula with sustained vision loss of ∼20/250 in the left eye when he was in his twenties. He subsequently presented in his thirties with acute vision loss in the right eye 3 times during a 70-month follow-up period. Each episode of vision loss in the right eye was preceded by several months of reaccumulation of vitelliform material in the macula apparent on fundus photographs, fluorescein angiograms, and optical coherence tomography, but no evidence of CNV on presentation. Each of the three episodes of vision loss in the right eye was followed by spontaneous gradual improvement in visual acuity over the next several months, correlating with decreasing amounts of the vitelliform material on clinical examination and fundus photographs. After the third documented recovery of visual acuity, at a time of stable vision, the patient developed CNV in the right eye, treated with intravitreal ranibizumab. Conclusion: This case demonstrates that vitelliform material can reaccumulate and resorb several times in Best disease, with temporary visual acuity decline after each episode of vitelliform material accumulation. There is a need for continued vigilance for the development of CNV in patients presenting with acute vision loss, although this patient developed CNV at a time of stable vision.
    09/2015; DOI:10.1097/ICB.0000000000000207
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    ABSTRACT: To determine the impact of ranibizumab 0.5 mg on patient-reported visual function over 36 months in individuals with visual impairment from diabetic macular edema. RESTORE comprises a phase 3, randomized, multicenter, 12-month core study, and a 24-month open-label extension study. Eyes assigned ranibizumab in the core study received ranibizumab for 36 months; eyes assigned laser monotherapy in the core study received ranibizumab during the extension. The primary outcome was least-squares mean change in National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) overall composite and subscale scores. Of 303 core study participants, 240 (79%) entered the extension, comprising 83 (35%) participants initially assigned ranibizumab, 83 (35%) assigned ranibizumab plus laser combination therapy, and 74 (31%) assigned laser monotherapy. Least-squares mean (standard error) change in NEI VFQ-25 composite score from baseline to month 12 (+5.9 [1.5]; +5.0 [1.5], for the ranibizumab and combination therapy groups, respectively) decreased by month 36 (+4.1 [1.7]; +4.0 [1.7], respectively, from baseline to month 36) following reduced injection frequency relative to the core study. At 36 months, the least-squares mean (standard error) change in the laser monotherapy group was similar to that in the ranibizumab groups (+4.1 [1.8]). Most subscale scores showed outcomes similar to that for the composite score. The greatest NEI VFQ-25 gains were consistently observed in participants for whom the study eye was the better-seeing eye. Patients entering the extension were not randomized, and 21% of the core study participants did not enter the extension, which may have affected the results. Gains in patient-reported visual function at month 12 among eyes receiving ranibizumab in the core study decreased slightly by 36 months. Eyes originally receiving laser monotherapy for 12 months, then ranibizumab for 24 months achieved similar gains by 36 months to eyes receiving ranibizumab for 36 months. NCT00687804 and NCT00906464.
    Current Medical Research and Opinion 09/2015; 31(11):1-28. DOI:10.1185/03007995.2015.1081880 · 2.65 Impact Factor
  • Ian C Han · Lawrence J Singerman · Alvin Schmaier · Neil M Bressler ·

    Jama Ophthalmology 07/2015; 133(10). DOI:10.1001/jamaophthalmol.2015.2414 · 3.32 Impact Factor
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    ABSTRACT: Age-related macular degeneration (AMD), left untreated, is the leading cause of vision loss in people older than 55. Severe central vision loss occurs in the advanced stage of the disease, characterized by either the in growth of choroidal neovascularization (CNV), termed the "wet" form, or by geographic atrophy (GA) of the retinal pigment epithelium (RPE) involving the center of the macula, termed the "dry" form. Tracking the change in GA area over time is important since it allows for the characterization of the effectiveness of GA treatments. Tracking GA evolution can be achieved by physicians performing manual delineation of GA area on retinal fundus images. However, manual GA delineation is time-consuming and subject to inter-and intra-observer variability. We have developed a fully automated GA segmentation algorithm in color fundus images that uses a supervised machine learning approach employing a random forest classifier. This algorithm is developed and tested using a dataset of images from the NIH-sponsored Age Related Eye Disease Study (AREDS). GA segmentation output was compared against a manual delineation by a retina specialist. Using 143 color fundus images from 55 different patient eyes, our algorithm achieved PPV of 0.82±0.19, and NPV of 0:95±0.07. This is the first study, to our knowledge, applying machine learning methods to GA segmentation on color fundus images and using AREDS imagery for testing. These preliminary results show promising evidence that machine learning methods may have utility in automated characterization of GA from color fundus images. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Computers in Biology and Medicine 07/2015; 65:124-136. DOI:10.1016/j.compbiomed.2015.06.018 · 1.24 Impact Factor
  • Lee M Jampol · Adam R Glassman · Neil M Bressler ·

    Jama Ophthalmology 06/2015; 133(9). DOI:10.1001/jamaophthalmol.2015.1880 · 3.32 Impact Factor
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    ABSTRACT: The approach to managing diabetic macular edema in eyes with previous vitrectomy is based on limited evidence. Therefore, an exploratory post hoc assessment of 3-year data from eyes with and without vitrectomy before randomization in a trial that evaluated ranibizumab + prompt or deferred laser for diabetic macular edema is presented. Visual acuity and optical coherence tomography outcomes were compared between eyes with and without previous vitrectomy. At baseline, eyes with previous vitrectomy (n = 25) had longer duration of diabetes, worse visual acuity, less thickened central subfield measurements on optical coherence tomography and were more apt to have worse diabetic retinopathy severity level or previous treatment for macular edema or cataract surgery than eyes without a history of vitrectomy (n = 335). Analyses adjusted for these baseline imbalances did not identify substantial differences between eyes with and without previous vitrectomy at each annual visit through 3 years for the favorable visual acuity, optical coherence tomography central subfield thickness, or volume outcomes, although optical coherence tomography improvement appeared slower in vitrectomy eyes during the first year. This study provides little evidence that the beneficial clinical outcomes for patients with center-involved diabetic macular edema treated with anti-vascular endothelial growth factor are affected in the long term by previous vitrectomy.
    Retina (Philadelphia, Pa.) 05/2015; DOI:10.1097/IAE.0000000000000617 · 3.24 Impact Factor
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    ABSTRACT: Optimization of glycemic control is critical to reduce the number of diabetes mellitus-related complications, but long-term success is challenging. Although vision loss is among the greatest fears of individuals with diabetes, comprehensive personalized diabetes education and risk assessments are not consistently used in ophthalmologic settings. To determine whether the point-of-care measurement of hemoglobin A1c (HbA1c) and personalized diabetes risk assessments performed during retinal ophthalmologic visits improve glycemic control as assessed by HbA1c level. Ophthalmologist office-based randomized, multicenter clinical trial in which investigators from 42 sites were randomly assigned to provide either a study-prescribed augmented diabetes assessment and education or the usual care. Adults with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent-than-annual follow-up (502 control participants and 488 intervention participants) and those with an annual follow-up (368 control participants and 388 intervention participants). Enrollment was from April 2011 through January 2013. Point-of-care measurements of HbA1c, blood pressure, and retinopathy severity; an individualized estimate of the risk of retinopathy progression derived from the findings from ophthalmologic visits; structured comparison and review of past and current clinical findings; and structured education with immediate assessment and feedback regarding participant's understanding. These interventions were performed at enrollment and at routine ophthalmic follow-up visits scheduled at least 12 weeks apart. Mean change in HbA1c level from baseline to 1-year follow-up. Secondary outcomes included body mass index, blood pressure, and responses to diabetes self-management practices and attitudes surveys. In the cohort with more-frequent-than-annual follow-ups, the mean (SD) change in HbA1c level at 1 year was -0.1% (1.5%) in the control group and -0.3% (1.4%) in the intervention group (adjusted mean difference, -0.09% [95% CI, -0.29% to 0.12%]; P = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA1c level was 0.0% (1.1%) in the control group and -0.1% (1.6%) in the intervention group (mean difference, -0.05% [95% CI, -0.27% to 0.18%]; P = .63). Results were similar for all secondary outcomes. Long-term optimization of glycemic control is not achieved by a majority of individuals with diabetes. The addition of personalized education and risk assessment during retinal ophthalmologic visits did not result in a reduction in HbA1c level compared with usual care over 1 year. These data suggest that optimizing glycemic control remains a substantive challenge requiring interventional paradigms other than those examined in our study. Identifier:NCT01323348.
    Jama Ophthalmology 05/2015; 133(8). DOI:10.1001/jamaophthalmol.2015.1312 · 3.32 Impact Factor
  • A.W. Kapre · M. Kimel · N. Bressler · R. Varma · E.H. Souied · C. Dolan · E. Tschosik · N. Leidy ·

    Value in Health 05/2015; 18(3):A184. DOI:10.1016/j.jval.2015.03.1062 · 3.28 Impact Factor
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    ABSTRACT: Background: The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. Methods: At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. Results: From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56). Conclusions: Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; number, NCT01627249.).
    New England Journal of Medicine 03/2015; 372(13):1193-1203. DOI:10.1056/NEJMoa1414264 · 55.87 Impact Factor
  • Neil M Bressler · Howard Bauchner ·
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    ABSTRACT: JAMA Ophthalmology has been notified by the University of Colorado Denver Anschutz Medical Campus that the university completed a scientific misconduct investigation involving research published by Rajendra Kadam, MPharm, and has determined that 10 papers with Kadam as an author contain falsified and/or fabricated data. For the article published in 2011 by Kadam et al in JAMA Ophthalmology, then known as Archives of Ophthalmology, the original liquid chromatographic/mass spectrometric data were not available to compare with the data used in the analysis, and the investigative committee was unable to validate the data reported in the study. Therefore, the committee was unable to reach any definitive conclusion related to the integrity or reliability of the data in this report. This Editorial Expression of Concern is to inform readers about possible concerns related to data therein. If additional information becomes available about the integrity of the data reported in this article, we will determine whether additional action is warranted.
    Jama Ophthalmology 03/2015; 133(4). DOI:10.1001/jamaophthalmol.2015.0631 · 3.32 Impact Factor
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    ABSTRACT: For the management of retinal disease, the use of intravitreous injections of anti-vascular endothelial growth factor has increased. Recent reports have suggested that this therapy may cause sustained elevation of intraocular pressure (IOP) and may potentially increase the risk of glaucoma for patients with retinal disease. To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments for eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab. An exploratory analysis was conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial. Study enrollment dates were from March 20, 2007, to December 17, 2008. Of 582 eyes (of 486 participants) with center-involved diabetic macular edema and no preexisting open-angle glaucoma, 260 were randomly assigned to receive a sham injection plus focal/grid laser treatment, and 322 were randomly assigned to receive ranibizumab plus deferred or prompt focal/grid laser treatment. The cumulative probability of sustained IOP elevation, defined as IOP of at least 22 mm Hg and an increase of at least 6 mm Hg from baseline at 2 consecutive visits, or the initiation or augmentation of ocular hypotensive therapy, through 3 years of follow-up. The mean (SD) baseline IOP in both treatment groups was 16 (3) mm Hg (range, 5-24 mm Hg). The cumulative probability of sustained IOP elevation or of initiation or augmentation of ocular hypotensive therapy by 3 years, after repeated ranibizumab injections, was 9.5% for the participants who received ranibizumab plus prompt or deferred focal/grid laser treatment vs 3.4% for the participants who received a sham injection plus focal/grid laser treatment (difference, 6.1% [99% CI, -0.2% to 12.3%]; hazard ratio, 2.9 [99% CI 1.0-7.9]; P = .01). The distribution of IOP and the change in IOP from baseline at each visit through 3 years were similar in each group. In eyes with center-involved diabetic macular edema and no prior open-angle glaucoma, repeated intravitreous injections of ranibizumab may increase the risk of sustained IOP elevation or the need for ocular hypotensive treatment. Clinicians should be aware of this risk and should consider this information when following up with patients who have received intravitreous injections of anti-vascular endothelial growth factor for the treatment of diabetic macular edema.
    Jama Ophthalmology 02/2015; 133(5). DOI:10.1001/jamaophthalmol.2015.186 · 3.32 Impact Factor
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    ABSTRACT: To estimate visual impairment (VI) and blindness avoided with intravitreal ranibizumab 0.3 mg treatment for central-involved diabetic macular edema (DME) among Hispanic and non-Hispanic white individuals in the United States. Population-based model simulating visual acuity (VA) outcomes over 2 years after diagnosis and treatment of DME. Visual acuity changes with and without ranibizumab were based on data from the RISE, RIDE, and DRCR Network trials. For the better-seeing eye, VA outcomes included VI, defined as worse than 20/40 in the better-seeing eye, and blindness, defined as VA of 20/200 or worse in the better-seeing eye. Incidence of 1 or both eyes with central-involved DME in 2010 were estimated based on the 2010 United States population, prevalence of diabetes mellitus, and 1-year central-involved DME incidence rate. Sixty-one percent of incident individuals had bilateral DME and 39% had unilateral DME, but DME could develop in the fellow eye. Cases of VI and blindness avoided with ranibizumab treatment. Among approximately 102 million Hispanic and non-Hispanic white individuals in the United States 45 years of age and older in 2010, an estimated 37 274 had central-involved DME and VI eligible for ranibizumab treatment. Compared with no ranibizumab treatment, the model predicted that ranibizumab 0.3 mg every 4 weeks would reduce the number of individuals with VI from 11 438 (95% simulation interval [SI], 7249-16 077) to 6304 (95% SI, 3921-8981), a 45% (95% SI, 36%-53%) reduction at 2 years. Ranibizumab would reduce the number of incident eyes with VA worse than 20/40 from 16 910 (95% SI, 10 729-23 577) to 9361 (95% SI, 5839-13 245), a 45% (95% SI, 38%-51%) reduction. Ranibizumab was estimated to reduce the number of individuals with legal blindness by 75% (95% SI, 58%-88%) and the number of incident eyes with VA of 20/200 or worse by 76% (95% SI, 63%-87%). This model suggests that ranibizumab 0.3 mg every 4 weeks substantially reduces prevalence of VI and legal blindness 2 years after initiating treatment among Hispanic and non-Hispanic white individuals in the United States with central-involved DME that has caused vision loss. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 02/2015; 122(5). DOI:10.1016/j.ophtha.2014.12.007 · 6.14 Impact Factor
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    ABSTRACT: To evaluate the effect of a topical, nonsteroidal antiinflammatory drug, nepafenac 0.1%, in eyes with noncentral diabetic macular edema. Multicenter, double-masked randomized trial. Individuals with good visual acuity and noncentral-involved diabetic macular edema were randomly assigned to nepafenac 0.1% (N = 61) or placebo (nepafenac vehicle, N = 64) 3 times a day for 12 months. The primary outcome was mean change in optical coherence tomography retinal volume at 12 months. Mean baseline retinal volume was 7.8 mm. At 12 months, in the nepafenac and placebo groups respectively, mean change in retinal volume was -0.03 mm and -0.02 mm (treatment group difference: -0.02, 95% confidence interval: -0.27 to 0.23, P = 0.89). Central-involved diabetic macular edema was present in 7 eyes (11%) and 9 eyes (14%) at the 12-month visit (P = 0.79), respectively. No differences in visual acuity outcomes were identified. One study participant developed a corneal melt after using nepafenac in the nonstudy eye, which had a history of severe dry eye. No additional safety concerns were evident. In eyes with noncentral diabetic macular edema and good visual acuity, topical nepafenac 0.1% 3 times daily for 1 year likely does not have a meaningful effect on optical coherence tomography-measured retinal thickness.
    Retina (Philadelphia, Pa.) 01/2015; 35(5). DOI:10.1097/IAE.0000000000000403 · 3.24 Impact Factor
  • Voraporn Chaikitmongkol · Neil M Bressler ·
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    ABSTRACT: Purpose: To describe the clinical and optical coherence tomography findings of an eye with diabetic macular edema that developed intraretinal fibrosis in an area previously occupied by lipid accumulating after the intravitreous ranibizumab treatment. Methods: Interventional case report. Results: An 85-year-old man presented with diabetic macular edema involving the center of the macula with a half disk area of lipid inferotemporal to the macula. He received ranibizumab treatments after the principles of the Diabetic Retinopathy Clinical Research Network retreatment guidelines. After 12 doses of intravitreous ranibizumab injections over 20 months, macular edema resolved, visual acuity improved from 20/63 to 20/40, and the central subfield thickness decreased from 404 μm to 234 μm. As the edema resolved, the area of lipid did not expand toward the fovea but was replaced by fibrosis occupying the area of lipid, only smaller in extent. Optical coherence tomography scans showed an intraretinal, dome-shaped hyperreflective area corresponding to the fibrosis. Conclusion: This case report, to our knowledge, provides the first documentation of intraretinal fibrosis replacing an area of lipid associated with diabetic macular edema after anti-vascular endothelial growth factor therapy, as had been described previously following laser photocoagulation for diabetic macular edema. Unlike some previous reports of lipid accumulating within the fovea with subsequent fibrosis corresponding to the metaplastic retinal pigment epithelium on histopathology, with or without laser treatment, the lipid in this case did not expand into the fovea before the development of fibrosis, and optical coherence tomography confirmed that the fibrosis was located in the intraretinal rather than the subretinal pigment epithelium space.
    Retinal Cases & Brief Reports 11/2014; 8(4):336-9. DOI:10.1097/ICB.0000000000000063
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    ABSTRACT: To report 5-year results from a previously reported trial evaluating intravitreal 0.5 mg ranibizumab with prompt versus deferred (for ≥24 weeks) focal/grid laser treatment for diabetic macular edema (DME). Multicenter, randomized clinical trial. Among participants from the trial with 3 years of follow-up who subsequently consented to a 2-year extension and survived through 5 years, 124 (97%) and 111 (92%) completed the 5-year visit in the prompt and deferred groups, respectively. Random assignment to ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and prompt or deferred (≥24 weeks) focal/grid laser treatment. Best-corrected visual acuity at the 5-year visit. The mean change in visual acuity letter score from baseline to the 5-year visit was +7.2 letters in the prompt laser group compared with +9.8 letters in the deferred laser group (mean difference, -2.6 letters; 95% confidence interval, -5.5 to +0.4 letters; P = 0.09). At the 5-year visit in the prompt versus deferred laser groups, there was vision loss of ≥10 letters in 9% versus 8%, an improvement of ≥10 letters in 46% versus 58%, and an improvement of ≥15 letters in 27% versus 38% of participants, respectively. From baseline to 5 years, 56% of participants in the deferred group did not receive laser. The median number of injections was 13 versus 17 in the prompt and deferral groups, including 54% and 45% receiving no injections during year 4 and 62% and 52% receiving no injections during year 5, respectively. Five-year results suggest focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better than deferring laser treatment for ≥24 weeks in eyes with DME involving the central macula with vision impairment. Although more than half of eyes in which laser treatment is deferred may avoid laser for at least 5 years, such eyes may require more injections to achieve these results when following this protocol. Most eyes treated with ranibizumab and either prompt or deferred laser maintain vision gains obtained by the first year through 5 years with little additional treatment after 3 years. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 10/2014; 122(2). DOI:10.1016/j.ophtha.2014.08.047 · 6.14 Impact Factor

Publication Stats

13k Citations
1,388.67 Total Impact Points


  • 1987-2015
    • Johns Hopkins University
      • • Wilmer Eye Institute
      • • Department of Epidemiology
      Baltimore, Maryland, United States
  • 1989-2014
    • Johns Hopkins Medicine
      • Wilmer Eye Institute
      Baltimore, Maryland, United States
  • 2008-2010
    • Jaeb Center for Health Research
      Tampa, Florida, United States
  • 1999-2010
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2009
    • Vanderbilt University
      Nashville, Michigan, United States
    • Penn State Hershey Medical Center and Penn State College of Medicine
      Hershey, Pennsylvania, United States
  • 2005
    • Emory University
      • Department of Ophthalmology
      Atlanta, Georgia, United States
  • 2002
    • University College London
      • Institute of Ophthalmology
      London, ENG, United Kingdom
  • 2000
    • Duke University
      Durham, North Carolina, United States
  • 1996
    • University of California, Santa Barbara
      • Neuroscience Research Institute
      Santa Barbara, CA, United States
  • 1992
    • Royal Victorian Eye and Ear Hospital
      Melbourne, Victoria, Australia
  • 1985-1987
    • Harvard Medical School
      Boston, Massachusetts, United States