著者: Neil H White, Wanjie Sun, Patricia A Cleary, Ronald P Danis, Matthew D Davis, Dean P Hainsworth, Larry D Hubbard, John M Lachin, David M Nathan
雑誌名: Arch Ophthalmol. 2008 Dec;126(12):1707-15. doi: 10.1001/archopht.126.12.1707.
Abstract/Text
OBJECTIVE: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.
METHODS: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.
RESULTS: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P < .001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P < .001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT.
CONCLUSION: The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.
TRIAL REGISTRATION: (clinicaltrials.gov) Identifiers: NCT00360815 and NCT00360893.
PMID
19064853 Arch Ophthalmol. 2008 Dec;126(12):1707-15. doi: 10.1001･･･
著者: DCCT/EDIC Research Group, Lloyd Paul Aiello, Wanjie Sun, Arup Das, Sapna Gangaputra, Szilard Kiss, Ronald Klein, Patricia A Cleary, John M Lachin, David M Nathan
雑誌名: N Engl J Med. 2015 Apr 30;372(18):1722-33. doi: 10.1056/NEJMoa1409463.
Abstract/Text
BACKGROUND: The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes.
METHODS: Between 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies.
RESULTS: Over a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P=0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P=0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P=0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up.
CONCLUSIONS: Intensive therapy in patients with type 1 diabetes was associated with a substantial reduction in the long-term risk of ocular surgery. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360893 and NCT00360815.).
PMID
25923552 N Engl J Med. 2015 Apr 30;372(18):1722-33. doi: 10.1056･･･
著者: Writing Team for the DCCT/EDIC Research Group, Rose A Gubitosi-Klug, Wanjie Sun, Patricia A Cleary, Barbara H Braffett, Lloyd Paul Aiello, Arup Das, William Tamborlane, Ronald Klein
雑誌名: JAMA Ophthalmol. 2016 Feb;134(2):137-45. doi: 10.1001/jamaophthalmol.2015.4606.
Abstract/Text
IMPORTANCE: Preservation of vision in patients with diabetes mellitus is critical. Interventions to improve glycemic control through early intensive treatment of diabetes reduce rates of severe retinopathy and preserve visual acuity.
OBJECTIVE: To assess the effects of prior intensive insulin treatment and risk factors on patient-reported visual function in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort.
DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 1184 participants with type 1 diabetes from the DCCT/EDIC study (randomized clinical trial followed by an observational follow-up study) who completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) during EDIC years 17 through 20 (September 1, 2009, through April 30, 2014) in 28 institutions across the United States and Canada.
MAIN OUTCOMES AND MEASURES: The primary outcome was the composite NEI-VFQ-25 score. Secondary outcomes were visual acuity (measured by the Early Treatment Diabetic Retinopathy Study protocol), retinopathy level (determined by masked grading of stereoscopic color fundus photographs), and NEI-VFQ-25 subscale scores. The composite NEI-VFQ-25 scale and its subscales were scored 0 to 100, corresponding to poor to excellent function, respectively.
RESULTS: The overall average NEI-VFQ-25 score for 1184 DCCT/EDIC participants (mean [SD] age, 52.3 [6.9] years; 48% female) with a 30-year duration of diabetes was high (all participants: median, 91.7; interquartile range [IQR], 89.7-96.9; intensive treatment [n = 605]: median, 94.7; IQR, 91.0-97.2; conventional treatment [n = 579]: median, 94.0; IQR, 88.4-96.1; P = .006 for intensive vs conventional). After adjustment for sex, age, hemoglobin A1c level, and retinopathy level at DCCT baseline, the former intensive treatment group had a significant, albeit modest, improvement in overall NEI-VFQ-25 score compared with the former conventional diabetes treatment group (median difference, -1.0; 95% CI, -1.7 to -0.3; P = .006). This beneficial treatment effect was fully attributed to the prior glycemic control in DCCT (explained treatment effect: 100%). Those with visual acuity worse than 20/100 reported the largest decline in visual function (median difference, -21.0; 95% CI, -40.5 to -1.6; P = .03).
CONCLUSIONS AND RELEVANCE: In the DCCT/EDIC cohort, patient-reported visual function remains high in both treatment groups, comparable to previous reports of overall health-related quality of life. Intensive diabetes therapy modestly improved NEI-VFQ-25 score 30 years after the start of the DCCT, the benefit underestimated owing to more nonparticipants from the conventional treatment group. Visual acuity had the greatest effect on patient-reported visual function from among all risk factors.
TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.
PMID
26584339 JAMA Ophthalmol. 2016 Feb;134(2):137-45. doi: 10.1001/j･･･
著者: Y Ohkubo, H Kishikawa, E Araki, T Miyata, S Isami, S Motoyoshi, Y Kojima, N Furuyoshi, M Shichiri
雑誌名: Diabetes Res Clin Pract. 1995 May;28(2):103-17.
Abstract/Text
To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.
PMID
7587918 Diabetes Res Clin Pract. 1995 May;28(2):103-17.
著者: A C Keech, P Mitchell, P A Summanen, J O'Day, T M E Davis, M S Moffitt, M-R Taskinen, R J Simes, D Tse, E Williamson, A Merrifield, L T Laatikainen, M C d'Emden, D C Crimet, R L O'Connell, P G Colman, FIELD study investigators
雑誌名: Lancet. 2007 Nov 17;370(9600):1687-97. doi: 10.1016/S0140-6736(07)61607-9. Epub 2007 Nov 7.
Abstract/Text
BACKGROUND: Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus.
METHODS: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481.
FINDINGS: Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022).
INTERPRETATION: Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.
PMID
17988728 Lancet. 2007 Nov 17;370(9600):1687-97. doi: 10.1016/S01･･･
著者: ACCORD Study Group, ACCORD Eye Study Group, Emily Y Chew, Walter T Ambrosius, Matthew D Davis, Ronald P Danis, Sapna Gangaputra, Craig M Greven, Larry Hubbard, Barbara A Esser, James F Lovato, Letitia H Perdue, David C Goff, William C Cushman, Henry N Ginsberg, Marshall B Elam, Saul Genuth, Hertzel C Gerstein, Ulrich Schubart, Lawrence J Fine
雑誌名: N Engl J Med. 2010 Jul 15;363(3):233-44. doi: 10.1056/NEJMoa1001288. Epub 2010 Jun 29.
Abstract/Text
BACKGROUND: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.
METHODS: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy.
RESULTS: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29).
CONCLUSIONS: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)
2010 Massachusetts Medical Society
PMID
20587587 N Engl J Med. 2010 Jul 15;363(3):233-44. doi: 10.1056/N･･･
著者: Pascale Massin, Francesco Bandello, Justus G Garweg, Lutz L Hansen, Simon P Harding, Michael Larsen, Paul Mitchell, Dianne Sharp, U E K Wolf-Schnurrbusch, Margarita Gekkieva, Andreas Weichselberger, Sebastian Wolf
雑誌名: Diabetes Care. 2010 Nov;33(11):2399-405. doi: 10.2337/dc10-0493.
Abstract/Text
OBJECTIVE: The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.
RESEARCH DESIGN AND METHODS: This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).
RESULTS: At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.
CONCLUSIONS: Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
PMID
20980427 Diabetes Care. 2010 Nov;33(11):2399-405. doi: 10.2337/d･･･
著者: Paul Mitchell, Francesco Bandello, Ursula Schmidt-Erfurth, Gabriele E Lang, Pascale Massin, Reinier O Schlingemann, Florian Sutter, Christian Simader, Gabriela Burian, Ortrud Gerstner, Andreas Weichselberger, RESTORE study group
雑誌名: Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
Abstract/Text
OBJECTIVE: To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).
DESIGN: A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.
PARTICIPANTS: We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.
METHODS: Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).
MAIN OUTCOME MEASURES: Mean average change in BCVA from baseline to month 1 through 12 and safety.
RESULTS: Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.
CONCLUSIONS: Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.
Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PMID
21459215 Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.o･･･
著者: Jean-François Korobelnik, Diana V Do, Ursula Schmidt-Erfurth, David S Boyer, Frank G Holz, Jeffrey S Heier, Edoardo Midena, Peter K Kaiser, Hiroko Terasaki, Dennis M Marcus, Quan D Nguyen, Glenn J Jaffe, Jason S Slakter, Christian Simader, Yuhwen Soo, Thomas Schmelter, George D Yancopoulos, Neil Stahl, Robert Vitti, Alyson J Berliner, Oliver Zeitz, Carola Metzig, David M Brown
雑誌名: Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.
Abstract/Text
PURPOSE: A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
DESIGN: Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME).
PARTICIPANTS: We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
METHODS: Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
MAIN OUTCOME MEASURES: The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
RESULTS: Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
CONCLUSIONS: At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PMID
25012934 Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j･･･
著者: Diabetic Retinopathy Clinical Research Network, John A Wells, Adam R Glassman, Allison R Ayala, Lee M Jampol, Lloyd Paul Aiello, Andrew N Antoszyk, Bambi Arnold-Bush, Carl W Baker, Neil M Bressler, David J Browning, Michael J Elman, Frederick L Ferris, Scott M Friedman, Michele Melia, Dante J Pieramici, Jennifer K Sun, Roy W Beck
雑誌名: N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.
Abstract/Text
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; ClinicalTrials.gov number, NCT01627249.).
PMID
25692915 N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.105･･･
著者: M Miyazaki, M Kubo, Y Kiyohara, K Okubo, H Nakamura, K Fujisawa, Y Hata, S Tokunaga, M Iida, Y Nose, T Ishibashi, Hisayama study
雑誌名: Diabetologia. 2004 Aug;47(8):1411-5. doi: 10.1007/s00125-004-1466-8. Epub 2004 Jul 28.
Abstract/Text
AIMS/HYPOTHESIS: The aims of this study were to compare the ability of tests measuring fasting plasma glucose, 2-h plasma glucose and HbA1c levels in predicting specific diabetic retinopathy, and to determine the cut-off level of each measurement for diagnosing diabetes in a Japanese population.
METHODS: In a total of 1637 subjects, fasting plasma glucose, 2-h plasma glucose and HbA1c levels were measured in a 75-g oral glucose tolerance test, and diabetic retinopathy was assessed by ophthalmic examination. We calculated receiver operating characteristic (ROC) curves as well as the prevalence of diabetic retinopathy by deciles of the distribution of these glycaemic measurements.
RESULTS: Of the subjects, 37 (2.3%) had diabetic retinopathy. The prevalence of retinopathy dramatically increased in the tenth decile of each variable. Analysis with ROC curves showed that the optimal cut-off levels for diagnosis of diabetes were 6.4 mmol/l for fasting plasma glucose, 11.1 mmol/l for 2-h plasma glucose, and 5.7% for HbA1c. The sensitivities for the cut-off point of the three measurements were identical (86.5%), and the specificities were similar (fasting plasma glucose 87.3%; 2-h plasma glucose 89.6%; HbA1c 90.1%). The area under the ROC curve for 2-h plasma glucose (96.1%) was slightly but not significantly larger than that for fasting plasma glucose (90.0%) and that for HbA1c (94.5%).
CONCLUSIONS/INTERPRETATION: . Our findings suggest that measuring fasting plasma glucose or HbA1c is just as useful as measuring 2-h plasma glucose for the diagnosis of diabetes, and that the cut-off point for diagnostic fasting plasma glucose level is lower than that of the current diagnostic criteria.
PMID
15309291 Diabetologia. 2004 Aug;47(8):1411-5. doi: 10.1007/s0012･･･
著者: R Kawasaki, J J Wang, T Y Wong, T Kayama, H Yamashita
雑誌名: Diabetes Obes Metab. 2008 Jun;10(6):514-5. doi: 10.1111/j.1463-1326.2007.00824.x.
Abstract/Text
PMID
18462198 Diabetes Obes Metab. 2008 Jun;10(6):514-5. doi: 10.1111･･･
著者: R Klein, B E Klein, S E Moss, M D Davis, D L DeMets
雑誌名: Arch Ophthalmol. 1984 Apr;102(4):520-6.
Abstract/Text
In a population-based study in southern Wisconsin, 996 insulin-taking, younger-onset diabetic persons were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 17% to 97.5% in persons with diabetes for less than five years and 15 or more years, respectively. Proliferative retinopathy varied from 1.2% to 67% in persons with diabetes for less than ten years and 35 or more years, respectively. For persons with diabetes of 10 years' duration or less, the Cox regression model relates the severity or retinopathy to longer duration, older age at examination, and higher levels of glycosylated hemoglobin. After ten years of diabetes, severity of retinopathy was related to longer duration, high levels of glycosylated hemoglobin, presence of proteinuria, higher diastolic BP, and male sex.
PMID
6367724 Arch Ophthalmol. 1984 Apr;102(4):520-6.
著者: R Klein, B E Klein, S E Moss, M D Davis, D L DeMets
雑誌名: Arch Ophthalmol. 1984 Apr;102(4):527-32.
Abstract/Text
In a population-based study in southern Wisconsin, 1,370 patients given diagnoses of diabetes at age 30 years or older were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 28.8% in persons who had diabetes for less than five years to 77.8% in persons who had diabetes for 15 or more years. The rate of proliferative diabetic retinopathy varied from 2.0% in persons who had diabetes for less than five years to 15.5% in persons who had diabetes for 15 or more years. By using the Cox regression model, the severity of retinopathy was found to be related to longer duration of diabetes, younger age at diagnosis, higher glycosylated hemoglobin levels, higher systolic BP, use of insulin, presence of proteinuria, and small body mass.
PMID
6367725 Arch Ophthalmol. 1984 Apr;102(4):527-32.
著者: Diabetes Control and Complications Trial Research Group
雑誌名: Diabetes Care. 2000 Aug;23(8):1084-91.
Abstract/Text
OBJECTIVE: To assess the effect of pregnancy on the development and progression of retinopathy and microalbuminuria in type 1 diabetes.
RESEARCH DESIGN AND METHODS: We conducted longitudinal analyses of the Diabetes Control and Complications Trial (DCCT), a multicenter controlled clinical trial that compared intensive treatment with conventional diabetes therapy and studied 180 women who had 270 pregnancies and 500 women who did not become pregnant during an average of 6.5 years of follow-up. Women assigned to the conventional treatment group were changed to intensive therapy if they were planning pregnancy or as soon as possible after conception. Fundus photography was performed every 6 months, and the urinary albumin excretion rate (AER) was measured annually.
RESULTS: Compared with nonpregnant women, pregnant women had a 1.63-fold greater risk of any worsening of retinopathy from before to during pregnancy (P < 0.05) in the intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not pregnant women in the conventional group (P < 0.001). In the conventional group, the odds of > or =3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during pregnancy in the intensive group, but not in the conventional group, was significantly elevated from the level at baseline, albeit in the normal range. Although individual patients had transient worsening of retinopathy during pregnancy, even to the proliferative level, at the end of the DCCT, mean levels of retinopathy and albuminuria in subjects who had become pregnant were similar to those in subjects who had not become pregnant within each treatment group.
CONCLUSIONS: Pregnancy in type 1 diabetes induces a transient increase in the risk of retinopathy; increased ophthalmologic surveillance is needed during pregnancy and the first year postpartum. The long-term risk of progression of early retinopathy and albumin excretion, however, does not appear to be increased by pregnancy.
PMID
10937502 Diabetes Care. 2000 Aug;23(8):1084-91.
著者:
雑誌名: N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
Abstract/Text
BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
PMID
8366922 N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/･･･
著者:
雑誌名: N Engl J Med. 2000 Feb 10;342(6):381-9. doi: 10.1056/NEJM200002103420603.
Abstract/Text
BACKGROUND: Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving near-normal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT).
METHODS: At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group.
RESULTS: The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1 percent and 7.2 percent, respectively) narrowed during follow-up (median during 4 years, 8.2 percent and 7.9 percent, respectively, P<0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72 percent to 87 percent, P<0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group.
CONCLUSIONS: The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.
PMID
10666428 N Engl J Med. 2000 Feb 10;342(6):381-9. doi: 10.1056/NE･･･
著者:
雑誌名: Lancet. 1998 Sep 12;352(9131):837-53.
Abstract/Text
BACKGROUND: Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.
METHODS: 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.
FINDINGS: Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).
INTERPRETATION: Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)
PMID
9742976 Lancet. 1998 Sep 12;352(9131):837-53.
著者:
雑誌名: Ophthalmology. 1981 Jul;88(7):583-600.
Abstract/Text
Additional follow-up confirms previous reports from the Diabetic Retinopathy Study (DRS) that photocoagulation, as used in the study, reduces the risk of severe visual loss by 50% or more. Decreases of visual acuity of one or more lines and constriction of peripheral visual field due to treatment were also observed in some eyes. These harmful effects were more frequent and more severe following the DRS xenon technique. The two-year risk of severe visual loss without treatment outweighs the risk of harmful treatment effects for two groups of eyes: (1) eyes with new vessels and preretinal or vitreous hemorrhage; and (2) eyes with new vessels on or within one disc diameter of the optic disc (NVD) equaling or exceeding 1/4 to 1/3 disc area in extent, (Fig 1), even in the absence of preretinal or vitreous hemorrhage. For eyes with these characteristics, prompt treatment is usually advisable. For eyes with less severe retinopathy, DRS findings do not provide a clear choice between prompt treatment or deferral unless progression to these more severe stages occurs.
PMID
7196564 Ophthalmology. 1981 Jul;88(7):583-600.
著者:
雑誌名: Ophthalmology. 1991 May;98(5 Suppl):766-85.
Abstract/Text
The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Follow-up examinations were scheduled at least every 4 months and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Eyes selected for early photocoagulation received one of four different combinations of scatter (panretinal) and focal treatment. This early treatment, compared with deferral of photocoagulation, was associated with a small reduction in the incidence of severe visual loss (visual acuity less than 5/200 at two consecutive visits), but 5-year rates were low in both the early treatment and deferral groups (2.6% and 3.7%, respectively). Adverse effects of scatter photocoagulation on visual acuity and visual field also were observed. These adverse effects were most evident in the months immediately following treatment and were less in eyes assigned to less extensive scatter photocoagulation. Provided careful follow-up can be maintained, scatter photocoagulation is not recommended for eyes with mild or moderate nonproliferative diabetic retinopathy. When retinopathy is more severe, scatter photocoagulation should be considered and usually should not be delayed if the eye has reached the high-risk proliferative stage. The ETDRS results demonstrate that, for eyes with macular edema, focal photocoagulation is effective in reducing the risk of moderate visual loss but that scatter photocoagulation is not. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. Focal treatment should be considered for eyes with macular edema that involves or threatens the center of the macula.
PMID
2062512 Ophthalmology. 1991 May;98(5 Suppl):766-85.
著者:
雑誌名: Arch Ophthalmol. 1990 Jul;108(7):958-64.
Abstract/Text
Six hundred sixteen eyes with recent severe diabetic vitreous hemorrhage reducing visual acuity to 5/200 or less for at least 1 month were randomly assigned to either early vitrectomy or deferral of vitrectomy for 1 year. The proportion of eyes with visual acuity of 10/20 or better was higher in the early vitrectomy group than in the deferral group throughout the 4-year follow-up period. Up to the 18-month visit, the early group had a higher proportion of eyes with visual acuity of no light perception. An increased chance of obtaining good vision with early vitrectomy was clearly present in the type I diabetes group, particularly in patients who developed severe vitreous hemorrhage after less than 20 years of diabetes, a patient group tending to have more severe proliferative retinopathy. This advantage was not found in the type II diabetes group, in which patients were older and tended to have less severe retinopathy. The findings of this and previous Diabetic Retinopathy Vitrectomy Study reports support early vitrectomy in eyes known or suspected to have very severe proliferative diabetic retinopathy as a means of increasing the chance of restoring or maintaining good vision.
PMID
2196036 Arch Ophthalmol. 1990 Jul;108(7):958-64.
著者: H Sone, A Katagiri, S Ishibashi, R Abe, Y Saito, T Murase, H Yamashita, Y Yajima, H Ito, Y Ohashi, Y Akanuma, N Yamada, JD Study Group
雑誌名: Horm Metab Res. 2002 Sep;34(9):509-15. doi: 10.1055/s-2002-34791.
Abstract/Text
BACKGROUND: Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes.
OBJECTIVE: The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results.
DESIGN: The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care.
PATIENTS: The study enrolled 2 205 patients with previously diagnosed type 2 diabetes.
INTERVENTION: The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer.
MEASUREMENTS: Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year.
RESULTS: Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available.
CONCLUSIONS: The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.
PMID
12384828 Horm Metab Res. 2002 Sep;34(9):509-15. doi: 10.1055/s-2･･･
著者: Diabetic Retinopathy Clinical Research Network (DRCR.net), Roy W Beck, Allison R Edwards, Lloyd P Aiello, Neil M Bressler, Frederick Ferris, Adam R Glassman, Elizabeth Hartnett, Michael S Ip, Judy E Kim, Craig Kollman
雑誌名: Arch Ophthalmol. 2009 Mar;127(3):245-51. doi: 10.1001/archophthalmol.2008.610.
Abstract/Text
OBJECTIVE: To report 3-year outcomes of patients who participated in a randomized trial evaluating 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone compared with focal/grid photocoagulation for treatment of diabetic macular edema.
METHODS: Eyes with diabetic macular edema and visual acuities of 20/40 to 20/320 were randomly assigned to focal/grid photocoagulation or 1 mg or 4 mg of triamcinolone. At the conclusion of the trial, 3-year follow-up data were available in 306 eyes.
RESULTS: Between 2 years (time of the primary outcome) and 3 years, more eyes improved than worsened in all 3 treatment groups. Change in visual acuity letter score from baseline to 3 years was +5 in the laser group and 0 in each triamcinolone group. The cumulative probability of cataract surgery by 3 years was 31%, 46%, and 83% in the laser and 1-mg and 4-mg triamcinolone groups, respectively. Intraocular pressure increased by more than 10 mm Hg at any visit in 4%, 18%, and 33% of eyes, respectively.
CONCLUSIONS: Results in a subset of randomized subjects who completed the 3-year follow-up are consistent with previously published 2-year results and do not indicate a long-term benefit of intravitreal triamcinolone relative to focal/grid photocoagulation in patients with diabetic macular edema similar to those studied in this clinical trial. Most eyes receiving 4 mg of triamcinolone as given in this study are likely to require cataract surgery.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00367133.
PMID
19273785 Arch Ophthalmol. 2009 Mar;127(3):245-51. doi: 10.1001/a･･･
著者: Diabetic Retinopathy Clinical Research Network, Michael J Elman, Lloyd Paul Aiello, Roy W Beck, Neil M Bressler, Susan B Bressler, Allison R Edwards, Frederick L Ferris, Scott M Friedman, Adam R Glassman, Kellee M Miller, Ingrid U Scott, Cynthia R Stockdale, Jennifer K Sun
雑誌名: Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.
Abstract/Text
OBJECTIVE: Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME).
DESIGN: Multicenter, randomized clinical trial.
PARTICIPANTS: A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea.
METHODS: Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system.
MAIN OUTCOME MEASURES: Best-corrected visual acuity and safety at 1 year.
RESULTS: The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes.
CONCLUSIONS: Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.
Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PMID
20427088 Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1･･･
著者: Anthony P Adamis, Michael Altaweel, Neil M Bressler, Emmett T Cunningham, Matthew D Davis, Mauro Goldbaum, Christine Gonzales, David R Guyer, Katz Barrett, Manju Patel, Macugen Diabetic Retinopathy Study Group
雑誌名: Ophthalmology. 2006 Jan;113(1):23-8. doi: 10.1016/j.ophtha.2005.10.012. Epub 2005 Dec 15.
Abstract/Text
OBJECTIVE: To study effects of intravitreal pegaptanib (Macugen) on retinal neovascularization.
DESIGN: Retrospective analysis of a randomized clinical trial. PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Individuals with retinal neovascularization identified from a multicenter, randomized, controlled trial evaluating pegaptanib for treatment of diabetic macular edema, with a best-corrected visual acuity letter score between 68 and 25 (approximate Snellen equivalent between 20/50 and 20/320) and receiving a sham injection or intravitreal pegaptanib (0.3 mg, 1 mg, 3 mg) administered at study entry, week 6, and week 12, with additional injections and/or focal photocoagulation as needed during the ensuing 18 weeks, up to a maximum of 6 pegaptanib/sham therapies, were evaluated. Scatter panretinal photocoagulation before study enrollment was permitted, but not within 6 months of randomization and study entry. Changes in retinal neovascularization were assessed on fundus photographs and fluorescein angiograms graded at a reading center in a masked fashion.
RESULTS: Of 172 participants, 19 had retinal neovascularization in the study eye at baseline. Excluding 1 who had scatter photocoagulation 13 days before randomization and 2 with no follow-up photographs, 1 of the remaining 16 subjects had panretinal photocoagulation during study follow-up. Of these 16 subjects, 8 of 13 (62%) in a pegaptanib treatment group (including the one receiving panretinal photocoagulation), 0 of 3 in the sham group, and 0 of 4 fellow (nonstudy) eyes showed either regression of neovascularization on fundus photographs or regression or absence of fluorescein leakage from neovascularization (or both) at 36 weeks. In 3 of 8 with regression, neovascularization progressed at week 52 after cessation of pegaptanib at week 30.
CONCLUSIONS: Most subjects with retinal neovascularization at baseline assigned to pegaptanib showed regression of neovascularization by week 36. These findings suggest a direct effect of pegaptanib upon retinal neovascularization in patients with diabetes mellitus.
PMID
16343627 Ophthalmology. 2006 Jan;113(1):23-8. doi: 10.1016/j.oph･･･
著者: Ri-ichiro Kohno, Yasuaki Hata, Yasutaka Mochizuki, Ryoichi Arita, Shuhei Kawahara, Takeshi Kita, Masanori Miyazaki, Toshio Hisatomi, Yasuhiro Ikeda, Lloyd Paul Aiello, Tatsuro Ishibashi
雑誌名: Am J Ophthalmol. 2010 Aug;150(2):223-229.e1. doi: 10.1016/j.ajo.2010.03.016. Epub 2010 Jun 9.
Abstract/Text
PURPOSE: To examine the histopathologic effect of a single intravitreal injection of bevacizumab on newly formed vessels in eyes with proliferative diabetic retinopathy (PDR).
DESIGN: Interventional case series and laboratory investigation.
METHODS: Two days after intravitreal injection of bevacizumab (1.25 mg/eye), pars plana vitrectomy or trabeculectomy was performed for the treatment of PDR or neovascular glaucoma (NVG) associated with PDR. Ten surgically removed preretinal proliferative tissues and 6 deep scleral flaps containing trabecular meshwork were fixed in 2% glutaraldehyde or 4% paraformaldehyde and were subjected to transmission electron microscopic analysis, immunohistochemical analysis, and terminal deoxyuridiine triphosphate (dUTP) nick-end labeling staining. Two surgically removed preretinal proliferative tissues and 2 deep scleral flaps from patients with PDR and NVG, but without preoperative intravitreal injection of bevacizumab (IVB), served as controls.
RESULTS: In control tissues, vascular endothelial cells possessed many fenestrations and were accompanied by pericytes. Apoptotic vascular endothelial cells frequently were observed in tissue after intravitreal injection of bevacizumab, whereas they were not observed in control tissues. Additionally, no apparent fenestration was observed in newly formed vessels from either proliferative tissue or trabecular meshwork after intravitreal injection of bevacizumab. In both PDR and NVG tissues after intravitreal injection of bevacizumab, overexpression of smooth muscle actin was observed in newly formed vessels, suggesting that the treatment may have increased pericytes on the vasculature as compared with control tissue.
CONCLUSIONS: Intravitreal injection of bevacizumab may induce changes in immature, newly formed vessels of PDR or NVG tissue, leading to endothelial apoptosis with vascular regression, while inducing normalization of premature vessels by increasing pericyte coverage and reducing vessel fenestration.
Copyright (c) 2010 Elsevier Inc. All rights reserved.
PMID
20542485 Am J Ophthalmol. 2010 Aug;150(2):223-229.e1. doi: 10.10･･･
著者: Ayman A Alkawas, Ezzat A Shahien, Atef M Hussein
雑誌名: J Glaucoma. 2010 Dec;19(9):622-6. doi: 10.1097/IJG.0b013e3181ccb794.
Abstract/Text
PURPOSE: The aim of this study was to evaluate the safety and efficacy of using intravitreal bevacizumab, panretinal photocoagulation, and trabeculectomy with mitomycin C in the management of neovascular glaucoma.
PATIENTS AND METHODS: The study included 17 eyes of 15 patients with neovascular glaucoma. Panretinal photocoagulation was performed combined with intravitreal bevacizumab injection (1.25 mg in 0.05 mL). A fornix-based conjunctival flap trabeculectomy with intraoperative mitomycin C (0.4mg/mL for 3min) was then performed.
RESULTS: The causes of neovascular glaucoma included: diabetic retinopathy (10 eyes), central retinal vein occlusion (5 eyes), and branch retinal vein occlusion (2 eyes). Complete regression of iris neovascularization after intravitreal bevacizumab injection and panretinal photocoagulation occurred in 14 eyes (82.4%). After trabeculectomy with mitomycin C, mean intraocular pressure was reduced from 42.9±4.2 mm Hg preoperatively to 15.1±2.2, 16.3±2.0, and 19.7±2.1 mm Hg at first week, first month, and sixth months postoperatively, respectively. This reduction was statistically significant (P<0.05). The mean number of antiglaucoma medications used before surgery was 2.8±0.4 (range: 2 to 3) that decreased to 0.8±0.6 (range: 0 to 3) after surgery. Postoperative hypotony (intraocular pressure 7 mm Hg) was observed in 17.6% (3 of 17 eyes), conjunctival dehiscence in 5.9%, shallow anterior chamber in 11.8%, hyphema in 23.5%, choroidal detachment in 11.8%, and epithelial corneal erosions related to applications of mitomycin C in 1 eye (5.9%).
CONCLUSIONS: Trabeculectomy with intraoperative mitomycin C after an adjunctive treatment with intravitreal bevacizumab and panretinal photocoagulation is a good treatment modality in the management of eyes with neovascular glaucoma.
PMID
20179624 J Glaucoma. 2010 Dec;19(9):622-6. doi: 10.1097/IJG.0b01･･･
著者: Suleyman Ciftci, Yildirim Bayezit Sakalar, Kaan Unlu, Ugur Keklikci, Ihsan Caca, Eyup Dogan
雑誌名: Eur J Ophthalmol. 2009 Nov-Dec;19(6):1028-33.
Abstract/Text
PURPOSE: To evaluate the clinical efficacy of intravitreal bevacizumab (IVB) combined with panretinal photocoagulation in patients with open angle neovascular glaucoma (NVG).
METHODS: Nine patients (9 eyes) with NVG participated in this study. Patients received IVB (1.25 mg) as the initial treatment for NVG and were followed up for at least 4 months. IVB was offered as the first treatment of choice to patients with NVG. Panretinal photocoagulation was performed as soon as feasible after the second week and completed in all patients the fourth week after IVB. The main outcome measures are resolution of INV, inhibition of peripheral anterior synechia (PAS), and controllability of intraocular pressure (IOP).
RESULTS: The mean follow-up period was 5.6+/-1.4 months (range, 4-9 months). The mean IOP before treatment was 35.1+/-9.7 mmHg (range, 24-56) under medication before IVB treatment. After IVB and after combined treatment, the mean IOP was reduced to 22.8+/-8.1 mmHg (range, 9-33) and 13.0+/-4.0 mmHg (range, 7-20), respectively. The mean referral INV was 3.6+/-0.4 grade (range, 3-4) and reduced to 1.6+/-0.4 (range 1-2) grade after IVB and 0.6+/-0.8 (range 0-2) grade after combined therapy. By IVB, combined panretinal photocoagulation recurrence of INV was not observed.
CONCLUSIONS: In NVG, IVB treatment can reduce iris and angle neovascularization and inhibits further PAS formation temporarily. Panretinal photocoagulation inhibits neovascularization constantly. Therefore, management of open angle NVG is more feasible with bevacizumab combined with panretinal photocoagulation.
PMID
19882572 Eur J Ophthalmol. 2009 Nov-Dec;19(6):1028-33.
著者: Julia Beutel, Swaantje Peters, Matthias Lüke, Sabin Aisenbrey, Peter Szurman, Martin S Spitzer, Efdal Yoeruek, Bevacizumab Study Group, Salvatore Grisanti
雑誌名: Acta Ophthalmol. 2010 Feb;88(1):103-9. doi: 10.1111/j.1755-3768.2008.01355.x. Epub 2009 Sep 20.
Abstract/Text
PURPOSE: We aimed to evaluate the longterm effects of intraocular bevacizumab (Avastin) injections as adjuvant treatment in patients with neovascular glaucoma.
METHODS: Twenty eyes of 18 consecutive patients with secondary neovascular glaucoma caused by proliferative diabetic retinopathy (n = 7), ischaemic central retinal vein occlusion (n = 7), ischaemic ophthalmopathy (n = 2) and retinal ischaemia resulting from persistent detachment (n = 2) were treated with intraocular bevacizumab injections (1.25 mg/0.05 ml) in addition to other treatments. The main outcome measure was the change in degree of iris rubeosis. Secondary outcomes included intraocular pressure (IOP), best corrected visual acuity (BCVA) and numbers of additional interventions or antiglaucoma medications administered after injection.
RESULTS: Mean (+/- standard deviation) follow-up was 67.7 +/- 13.8 weeks (range 50-93 weeks). At the last follow-up, complete regression of rubeosis was detectable in five (20%) eyes, incomplete regression in seven (35%), stabilization in six (30%), and an increase in two (10%) eyes. Mean IOP was 26.0 +/- 8.9 mmHg at baseline and significantly decreased to 14.75 +/- 5.3 mmHg at the last follow-up visit (p = 0.000005). Mean baseline BCVA (logMAR [logarithm of the minimum angle of resolution] 1.43 +/- 0.89) was stabilized during the follow-up period (logMAR 1.5 +/- 0.98). Patients received an average of 2.75 injections. Additional treatments were laser photocoagulation in 13 (65%) eyes, cyclodestructive procedure in 14 (70%), cryopexy in six (30%), drainage procedures in two (10%), and vitrectomy in five (25%) eyes.
CONCLUSIONS: Bevacizumab may be beneficial as adjuvant treatment in neovascular glaucoma because of its anti-angiogenic properties and its ability to prevent establishment or progression of angular obstruction. The causative disease inducing the angiogenic process requires treatment in all cases. Antiglaucoma treatment is needed in cases of persistent elevated IOP.
PMID
18811641 Acta Ophthalmol. 2010 Feb;88(1):103-9. doi: 10.1111/j.1･･･
著者: Yanrong Jiang, Xiaoying Liang, Xiaoxin Li, Yong Tao, Kai Wang
雑誌名: Acta Ophthalmol. 2009 Nov;87(7):736-40. doi: 10.1111/j.1755-3768.2008.01353.x. Epub 2008 Sep 18.
Abstract/Text
PURPOSE: To evaluate the therapeutic effect of intravitreal bevacizumab (Avastin) (IVB) in the treatment of iris neovascularization (INV) in proliferative diabetic retinopathy (PDR).
METHODS: A retrospective analysis on data collected from 28 eyes of 22 patients with PDR was performed. The analysis included grading of INV, visual acuity (VA) and intraocular pressure (IOP) prior to and after IVB treatment.
RESULTS: Significant regression was noted in 20 eyes (71.4%); six eyes (21.4%) showed partial regression; no change or worsening was observed in two eyes (7.2%). VA (measured with a Snellen acuity chart) improved in five eyes (17.9%) while the remaining 23 eyes (82.1%) had no improvement. In the 11 eyes with preoperative neovascular glaucoma, IOP decreased in 10 eyes (91%) and increased in one eye (9%) after treatment.
CONCLUSION: IVB treatment of INV in PDR patients shows a promising short-term result. Further studies are needed to evaluate long-term results.
PMID
18803622 Acta Ophthalmol. 2009 Nov;87(7):736-40. doi: 10.1111/j.･･･
