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Liraglutide Treatment Does Not Induce Changes in the Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Diabetic Retinopathy.
Arendt Nielsen, T, Sega, R, Uggerhøj Andersen, C, Vorum, H, Drewes, AM, Jakobsen, PE, Brock, B, Brock, C
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2022;(1):114-121
Abstract
Purpose: Liraglutide treatment has shown promising anti-inflammatory and nerve regenerative results in preclinical and clinical trials. We sought to assess if liraglutide treatment would induce nerve regeneration through its anti-inflammatory and neurotrophic mechanisms by increasing peripapillary retinal nerve fiber layer (RNFL) thickness in individuals with long-term type 1 diabetes. Methods: Secondary analyses were performed on a prospective, double-blinded, randomized, placebo-controlled trial on adults with type 1 diabetes, distal symmetric polyneuropathy (DSPN), and confirmed diabetic retinopathy, who were randomized 1:1 to either 26 weeks placebo or liraglutide treatment. The primary endpoint was a change in peripapillary RNFL thickness between treatments, assessed by optical coherence tomography. Results: Thirty-seven participants were included in the secondary analysis. No differences in mean peripapillary RNFL thickness (overall ΔMean RNFL thickness; liraglutide -1 (±8) μm (-1%) vs. placebo -1 (±5) μm (-1%), P = 0.78, n = 37) or any of the quadrants. Peripapillary RNFL thicknesses were shown between treatments in either nonproliferative (ΔMean RNFL thickness; liraglutide -1 (±5) μm (-1%) vs. placebo 0 (±4) μm (0%), P = 0.80, N = 26) or proliferative diabetic retinopathy subgroup (ΔMean RNFL thickness; liraglutide -2 (±14) μm (-3%) vs. placebo -1 (±6) μm (-2%), P = 0.88, N = 11). Conclusions: In this study, 26 weeks of liraglutide treatment did not induce measurable changes in the assessed optic nerve thickness. Thus, this methodology does not support the induction of substantial nerve regeneration in this cohort with established retinopathy and DSPN. The trial was approved by the Danish Health and Medicines Authority. Informed consent was obtained from all participants. TODINELI study: EUDRA CT 2013-004375-12, Ethics Ref: N-20130077 Clinical trial registration number: clinicaltrials.gov NCT02138045.
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Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT.
Broadbent, DM, Wang, A, Cheyne, CP, James, M, Lathe, J, Stratton, IM, Roberts, J, Moitt, T, Vora, JP, Gabbay, M, et al
Diabetologia. 2021;(1):56-69
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AIMS/HYPOTHESIS Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide-ranging input from individuals with diabetes. METHODS This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives. RESULTS A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference -1.0 [95% CI -3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non-inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference -0.3 [95% CI -1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality-adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero; multiple imputation supported the dominance of individualised screening. Incremental cost savings per person with individualised screening were £17.34 (95% CI 17.02, 17.67) from the National Health Service perspective and £23.11 (95% CI 22.73, 23.53) from the societal perspective, representing a 21% reduction in overall programme costs. Overall, 43.2% fewer screening appointments were required in the individualised arm. CONCLUSIONS/INTERPRETATION Stakeholders involved in diabetes care can be reassured by this study, which is the largest ophthalmic RCT in diabetic retinopathy screening to date, that extended and individualised, variable-interval, risk-based screening is feasible and can be safely and cost-effectively introduced in established systematic programmes. Because of the 2 year time horizon of the trial and the long time frame of the disease, robust monitoring of attendance and retinopathy rates should be included in any future implementation. TRIAL REGISTRATION ISRCTN 87561257 FUNDING The study was funded by the UK National Institute for Health Research. Graphical abstract.
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The effect of educational program based on theory of planned behavior on promoting retinopathy preventive behaviors in patients with type 2 diabetes: RCT.
Hosseini, SS, Shamsi, M, Khorsandi, M, Moradzadeh, R
BMC endocrine disorders. 2021;(1):17
Abstract
BACKGROUND Diabetic retinopathy is the most common microvascular complication of diabetes and it is a leading cause of visual impairment and blindness among patients with diabetes. This study aimed to investigate the effect of educational program based on Theory of Planned Behavior (TPB) on promoting retinopathy preventive behaviors in patients with type 2 diabetes. METHODS The present study is an educational randomized controlled trial research that was conducted on 94 patients with type 2 diabetes who had gone to diabetes clinic. The samples were randomly assigned to the intervention (N = 47) and control groups (N = 47). Data collection instrument was a researcher-made questionnaire based on TPB and FBS and HbA1C tests. Then, educational program was performed for the intervention group through four educational sessions. After 3 months, data collection was repeated for the two groups and FBS, HbA1C testes were done again and data were analyzed. RESULTS The performance of the intervention group on preventive behaviors of retinopathy increased from 2.48 ± 1.42 to 4.48 45 1.45 after the education (p < 0.001). The mean of FBS and HbA1c in the intervention group also decreased after the intervention (P < 0.05). CONCLUSION Applying the TPB model proved is very effective in developing an educational program for patients with diabetes, to control their blood sugar and enhance preventive behaviors of retinopathy. Besides such programs, follow-up education for controlling and monitoring are highly recommended. This theory serves as a helpful theoretical framework for health-related behaviors and can be an appropriate pattern to plan for educational interventions. TRIAL REGISTRATION This trial has been registered at Iranian Registry of Clinical Trials, IRCT20180819040834N1 . Prospectively registered 8 Apr 2019, https://en.irct.ir/trial/38401.
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Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study.
de Mello, VD, Selander, T, Lindström, J, Tuomilehto, J, Uusitupa, M, Kaarniranta, K
Nutrients. 2021;(12)
Abstract
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40-64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.
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Effectiveness and Safety of Coadministration of Intravitreal Dexamethasone Implant and Silicone Oil Endotamponade for Proliferative Diabetic Retinopathy with Tractional Diabetic Macular Edema.
Altun, A, Kanar, HS, Aki, SF, Arsan, A, Hacisalihoglu, A
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2021;(2):131-137
Abstract
Purpose: To investigate the efficacy and safety of coadministered intravitreal dexamethasone (IVD) implant and silicone oil endotamponade during pars plana vitrectomy (PPV) for the treatment of proliferative diabetic retinopathy (PDR) with tractional diabetic macular edema (DME). Methods: In this prospective, controlled, and randomized clinical study, the eyes with PDR and vitreomacular traction syndrome that underwent PPV with silicone oil endotamponade were divided into 2 groups. Group 1 was defined as the control group, and no other procedures were performed. IVD was implanted to the eyes in Group 2. In both groups, panretinal photocoagulation was completed to the missed areas during PPV. All cases followed for 6 months, postoperatively. Retinal findings were followed with optical coherence tomography and fluorescein fundus angiography. Results: A total of 52 eyes of 52 patients were included in the study. Twenty-six eyes of 23 patients were included in both groups. The improvement in best corrected visual acuity was statistically significantly higher in Group 2 (P > 0.05). In the postoperative period, the DME development rate and intravitreal ranibizumab (IVR) injection requirement were significantly higher in Group 1 (P > 0.05). There was no statistically significant difference in the proliferative vitroretinopathy development rate between the groups (P < 0.05). Conclusion: Coadministration of IVD implant and silicone oil endotamponade to the eyes with PDR during vitrectomy seems to be safe and effective application and may decrease the rate of DME and the requirement of IVR injection.
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Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study.
Babiuch, A, Wykoff, CC, Hach, J, Srivastava, S, Talcott, KE, Yu, HJ, Nittala, M, Sadda, S, Ip, MS, Le, T, et al
The British journal of ophthalmology. 2021;(8):1111-1115
Abstract
BACKGROUND/AIMS: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform. METHODS RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively. RESULTS The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group. CONCLUSION Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact. TRIAL REGISTRATION NUMBER NCT02863354.
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Attendance Rate in Patients with Diabetic Macular Edema Receiving Short Messages.
Kumar, G, Velu, S, Prakash, VJ, Kumar, S, Sivaprasad, S, Sharma, A, Raman, R
Ophthalmology. Retina. 2021;(10):1054-1056
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Four-Year Screening Interval and Vision-Threatening Retinopathy in Type 2 Diabetes Patients With Good Glycemic Control.
Tsujimoto, T, Kajio, H
Mayo Clinic proceedings. 2021;(2):322-331
Abstract
OBJECTIVE To assess whether vision-threatening retinopathy developed after 4 years in patients with type 2 diabetes with good glycemic control during follow-up. PATIENTS AND METHODS Using data from the Action to Control Cardiovascular Risk in Diabetes and Action to Control Cardiovascular Risk in Diabetes Follow-on studies (conducted from January 1, 2001, to October 14, 2014), we investigated the incidence of vision-threatening retinopathy after 4 years in patients with type 2 diabetes with good or poor glycemic control. Patients with proliferative diabetic retinopathy at baseline were excluded. Vision-threatening retinopathy was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, laser photocoagulation, or vitrectomy. Good and poor glycemic control was defined as mean glycated hemoglobin level less than 7% and 7% or greater during follow-up, respectively. RESULTS This study included 2285 patients. Among patients with no retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was 0% (0 of 386) and 0.8% (6 of 721) in those with good and poor glycemic control, respectively (P=.54). Similarly, severe retinopathy was not observed at 8 years in patients who did not have retinopathy at 4 years. Among patients with mild to moderate nonproliferative diabetic retinopathy at baseline, the 4-year incidence of vision-threatening retinopathy was significantly higher in those with poor glycemic control than in those with good glycemic control (9.7% [77 of 790] vs 4.4% [13 of 297]; P=.004). Additionally, the remission rate of diabetic retinopathy was low in patients with a long duration of diabetes. Four-year incidences of vision-threatening retinopathy were higher in patients with retinopathy at baseline who had poorer glycemic control and longer durations of diabetes. CONCLUSION It may be safe to extend screening intervals for diabetic retinopathy to 4 years or longer in patients with type 2 diabetes with no retinopathy.
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Combination of Intravitreal Bevacizumab and Topical Dorzolamide versus Intravitreal Bevacizumab Alone for Diabetic Macular Edema: A Randomized Contralateral Clinical Trial.
Fazel, F, Nikpour, H, Pourazizi, M
BioMed research international. 2020;:6794391
Abstract
PURPOSE To evaluate the efficacy of three intravitreal bevacizumab (IVB) injections versus the same combined with 2% of topical dorzolamide in the treatment of diabetic macular edema (DME). METHODS In this randomized double-masked clinical trial, 32 eyes of 16 treatment-naive patients with bilateral DME were enrolled. The eyes were randomly assigned to receive three monthly injections of IVB (1.25 mg) plus topical dorzolamide 2% twice daily or IVB (1.25 mg) plus topical artificial tear twice daily. Best-corrected visual acuity (BCVA) was the primary outcome of the study followed by the central macular thickness (CMT) and central macular volume (CMV) as the secondary outcomes. RESULTS Mean BCVA changes were insignificant in both groups. It changed from 0.21 ± 0.08 logMAR at baseline to 0.23 ± 0.09 (P=0.24) in the combination group and from 0.18 ± 0.09 logMAR to 0.21 ± 0.09 (P=0.11) in the IVB alone group, at 3 months, respectively. Changes in mean CMT and CMV were significant in both groups. However, the difference between the groups was not significant at all the visits. In the study, no major ocular complication or systemic side effects were noted regarding IVB or topical dorzolamide. CONCLUSION This randomized contralateral clinical trial demonstrated that adjuvant topical dorzolamide with IVB injection had no additional effects on IVB in the treatment of DME over a three-month course. This trial is registered with the Iranian Registry of Clinical Trials under the registration code IRCT20131229015975N5.
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Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.
Besirli, CG, Smith, SJ, Zacks, DN, Gardner, TW, Pipe, KP, Musch, DC, Shah, AR
Ophthalmology. Retina. 2020;(10):979-986
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PURPOSE To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.