scholarly journals Lightmasks that prevent dark adaptation for non-central diabetic macular oedema: the CLEOPATRA RCT

2019 ◽  
Vol 6 (2) ◽  
pp. 1-78
Author(s):  
Sobha Sivaprasad ◽  
Joana Vasconcelos ◽  
Helen Holmes ◽  
Caroline Murphy ◽  
Joanna Kelly ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Dark Adaptation ◽  
Standard Care ◽  
Diabetic Macular Oedema ◽  
Clinical Effectiveness ◽  
Phase Iii ◽  
Mechanistic Study ◽  
Controlled Clinical Trial

Background Hypoxia may contribute to the development and progression of diabetic macular oedema (DMO) and diabetic retinopathy. The photoreceptors are the most metabolically active cells in the retina and the rod photoreceptors consume the maximal amount of oxygen for dark adaptation. Therefore, a lightmask emitting 500- to 505-nm light and worn at night during sleep may prevent rod-related dark adaptation and, thereby, reduce the retinal oxygen consumption and improve or prevent progression of DMO and diabetic retinopathy as evidenced in small short-term studies. Objectives The clinical effectiveness and safety of using a lightmask to prevent dark adaptation as a treatment and preventative option was evaluated for DMO over 24 months. Design A Phase III, multicentre, prospective, single-masked, randomised controlled clinical trial that evaluated the clinical effectiveness and safety of a lightmask that prevents dark adaptation to treat and prevent non-central DMO versus standard care (i.e. non-lightmask arm) at 24 months. A subset of participants also enrolled for a mechanistic substudy that evaluated the role of hypoxia in DMO. Setting Fifteen NHS clinical sites in the UK. Participants Adults with non-centre-involving DMO. Intervention The participants were randomly assigned (1 : 1) to being offered a lightmask (Noctura 400 Sleep Masks, Polyphotonix Medical Ltd, Durham, UK) to wear at night during sleep to prevent dark adaptation or to the non-lightmask arm (standard care) for 24 months. The participants were evaluated every 4 months. Main outcome measure The primary outcome was defined as a change in retinal thickness at the zone of maximum thickness measured by spectral domain optical coherence tomography at 24 months in the study eye, analysed using a linear mixed-effects model that estimated adjusted treatment effects at both 12 and 24 months. Results A total of 308 participants were recruited between April 2014 and May 2015. A total of 155 participants in the lightmask arm and 153 in the control arm contributed to the intention-to-treat strategy. The lightmask arm did not show any difference in effect compared with the non-lightmask arm [adjusted mean difference between arms –0.65 µm, 95% confidence interval –6.90 to 5.59 µm; p = 0.84). The compliance of wearing the lightmask was suboptimal, as recorded electronically, from the returned lightmasks. There were no lightmask-related severe adverse events. The mechanistic study aimed at studying the effect of improving hypoxia by inhaling 100% oxygen or by offering lightmasks to wear during sleep at night over 12 months did not demonstrate any clinically beneficial effect on DMO. Conclusion The lightmask, as offered in this trial to prevent dark adaptation, did not show any treatment or preventative effect in participants with non-central oedema or diabetic retinopathy at 24 months. No effect was seen as early as 4 months when compliance was higher. Future work Future research is needed to evaluate the role of rod-induced hypoxia in the pathogenesis of DMO and diabetic retinopathy. Trial registration Current Controlled Trials ISRCTN85596558. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. The report will be published in full in Efficacy and Mechanism Evaluation; Vol. 6, No. 2. See the NIHR Journals Library website for further project information. The lightmasks were purchased at a discounted rate from Polyphotonix Medical Ltd.

scholarly journals Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1683
Author(s):  
Milagros Mateos-Olivares ◽  
Luis García-Onrubia ◽  
Fco. Javier Valentín-Bravo ◽  
Rogelio González-Sarmiento ◽  
Maribel Lopez-Galvez ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Standard Therapy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Rho Kinase ◽  
Diabetic Macular Oedema ◽  
New Drugs ◽  
Anti Vegf

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

Long-term outcomes with as-needed aflibercept in diabetic macular oedema: 2-year outcomes of the ENDURANCE extension study

2017 ◽  
Vol 102 (5) ◽  
pp. 631-636 ◽  
Author(s):  
Charles C Wykoff ◽  
William C Ou ◽  
Rahul N Khurana ◽  
David M Brown ◽  
W Lloyd Clark ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Phase Iii ◽  
Extension Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Intravitreal Aflibercept ◽  
The Mean

Background/aimsTo evaluate the efficacy and safety of individualised 2.0 mg intravitreal aflibercept retreatment for diabetic macular oedema (DME) through the fifth year of management.MethodsThis is a phase IV, 2-year, open-label extension study. Sixty patients completing the 3-year VISTA DME (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) phase III trial enrolled in the ENDURANCE (Long-Term Efficacy and Safety of Intravitreal Aflibercept for the Treatment of DME in Subjects Who Completed the VISTA DME Trial) extension study. All patients received aflibercept in the presence of clinically relevant DME. Intervals between visits were prescribed according to disease activity. The main outcome measure was mean aflibercept injections given through 2 years.ResultsA mean of 7.7 aflibercept injections were administered through 2 years. Fifteen (25%) patients required no retreatment and 48% (n=29) of patients received five or fewer injections through 2 years. Among patients who received at least one aflibercept retreatment during ENDURANCE, the mean number of injections through 2 years was 9.5. The mean visual acuity and central retinal thickness gains achieved during VISTA DME were maintained and stable during ENDURANCE. The most notable safety signal was progression of diabetic retinopathy. Six (10%) patients converted from non-proliferative to proliferative diabetic retinopathy (PDR), and a total of eight patients experienced PDR events occurring at a mean of 387 days following the previous aflibercept treatment.ConclusionThe need for aflibercept retreatment was substantially reduced in the fourth and fifth years of aflibercept dosing for DME following initiation of therapy in the VISTA DME trial. While vision gains achieved during the 3-year VISTA DME trial were maintained through ENDURANCE with a reduced treatment burden, clinically relevant worsening of diabetic retinopathy was observed with progression to PDR in 10% of the eyes.Trial registration numberNCT02299336

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab

2020 ◽  
pp. 112067212092727
Author(s):  
Marko Lukic ◽  
Gwyn Williams ◽  
Zaid Shalchi ◽  
Praveen J Patel ◽  
Philip G Hykin ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Early Treatment ◽  
Macular Oedema ◽  
Real Life ◽  
Diabetic Macular Oedema ◽  
Foveal Thickness ◽  
Macular Volume ◽  
Central Foveal Thickness ◽  
The Mean

Purpose To assess visual and optical coherence tomography–derived anatomical outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in patients switched from intravitreal ranibizumab (Lucentis®). Design Retrospective, cohort study. Participants Ninety eyes (of 67 patients) receiving intravitreal anti–vascular endothelial growth factor therapy were included. Methods This is a retrospective, real-life, cohort study. Each patient had visual acuity measurements and optical coherence tomography scans performed at baseline and 12 months after the first injection of aflibercept was given. Main Outcome Measures We measured visual acuities in Early Treatment Diabetic Retinopathy Study letters, central foveal thickness and macular volume at baseline and at 12 months after the first aflibercept injection was given. Results Ninety switched eyes were included in this study. The mean (standard deviation) visual acuity was 63 (15.78) Early Treatment Diabetic Retinopathy Study letters. At baseline, the mean (standard deviation) central foveal thickness was 417.7 (158.4) μm and the mean macular volume was 9.96 (2.44) mm3. Mean change in visual acuity was +4 Early Treatment Diabetic Retinopathy Study letters (p = 0.0053). The mean change in macular volume was −1.53 mm 3 in SW group (p = 0.21), while the change in central foveal thickness was −136.8 μm (p = 0.69). Conclusion There was a significant improvement in visual acuity and in anatomical outcomes in the switched group at 12 months after commencing treatment with aflibercept for diabetic macular oedema.

scholarly journals Extended real-world experience with the ILUVIEN® (fluocinolone acetonide) implant in the United Kingdom: 3-year results from the Medisoft® audit study

Eye ◽  
2021 ◽  
Author(s):  
Clare Bailey ◽  
◽  
Usha Chakravarthy ◽  
Andrew Lotery ◽  
Geeta Menon ◽  
...  
Keyword(s):  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Clinical Effectiveness ◽  
Fluocinolone Acetonide ◽  
Prior History ◽  
Foveal Thickness ◽  
Central Foveal Thickness ◽  
Laser Trabeculoplasty ◽  
Retrospective Audit ◽  
History Of

Abstract Background This study aimed to assess the long-term effectiveness of the 0.2 μg/day fluocinolone acetonide (FAc) implant over ≥3 years for patients with diabetic macular oedema. Methods A retrospective audit of pseudo-anonymised data from patients with chronic diabetic macular oedema (cDMO) and treated with the FAc implant across 14 UK clinical sites. Safety and clinical effectiveness were measured. Results Two-hundred and fifty-six eyes had ≥3 years of follow-up (mean 4.28 years), during which a mean of 1.14 FAc implants were used per eye. Mean best-recorded visual acuity (BRVA) increased from 52.6 to 56.7 letters at month 3 and remained stable thereafter; this trend was also seen in pseudophakic eyes. The proportion of patients attaining a BRVA ≥6/12 increased from 17% at baseline to 27% 1 month after FAc implant and remained stable above 30% from month 12 onwards. Eyes with no prior history of intraocular pressure (IOP)-related events required significantly less treatment-emergent IOP-lowering medication than those with a prior history of IOP events (17.9% vs. 50.0% of eyes; p < 0.001). The incidence of an IOP increase of ≥10 mmHg, use of IOP-lowering medication, laser trabeculoplasty and IOP-lowering surgery was 28.9%, 29.7%, 0.8% and 2.7%, respectively, for the whole cohort. There were significant reductions in mean central foveal thickness and macular volume (p < 0.001). Conclusions The FAc implant was well tolerated, with predictable and manageable IOP-related events while delivering a continuous microdose of corticosteroid to eyes with cDMO, providing prolonged vision preservation and a reduced number of treatments.

scholarly journals Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study

2021 ◽  
pp. bjophthalmol-2020-318690
Author(s):  
Kun Liu ◽  
Hanying Wang ◽  
Wei He ◽  
Jian Ye ◽  
Yanping Song ◽  
...  
Keyword(s):  
Macular Oedema ◽  
Laser Photocoagulation ◽  
Sham Group ◽  
Controlled Trial ◽  
Diabetic Macular Oedema ◽  
Intravitreal Injections ◽  
Phase Iii ◽  
Extension Study ◽  
Open Label ◽  
Open Label Extension

BackgroundTo demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).MethodsA 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.ResultsA total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.ConclusionThe use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.Trial registration numberNCT02194634.

scholarly journals Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

2021 ◽  
Vol 22 (8) ◽  
pp. 4020
Author(s):  
Enrique Antonio Alfonso-Muñoz ◽  
Raquel Burggraaf-Sánchez de las Matas ◽  
Jorge Mataix Boronat ◽  
Julio César Molina Martín ◽  
Carmen Desco
Keyword(s):  
Diabetic Retinopathy ◽  
Diabetic Macular Oedema ◽  
Complementary Therapy ◽  
Antioxidant Supplementation ◽  
Current Management ◽  
Adult Type ◽  
Aged People

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

Non-mydriatic ultrawide field scanning laser ophthalmoscopy compared with dilated fundal examination for assessment of diabetic retinopathy and diabetic macular oedema in Chinese individuals with diabetes mellitus

2018 ◽  
Vol 103 (9) ◽  
pp. 1327-1331 ◽  
Author(s):  
Simon K H Szeto ◽  
Raymond Wong ◽  
Jerry Lok ◽  
Fangyao Tang ◽  
Zihan Sun ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Clinical Examination ◽  
Macular Oedema ◽  
Chinese Population ◽  
Retrospective Cohort ◽  
Diabetic Macular Oedema ◽  
Scanning Laser ◽  
Scanning Laser Ophthalmoscopy ◽  
Chinese Cohort ◽  
Clinical Grading

AimsTo evaluate the performance of ultrawide field scanning laser ophthalmoscopy (UWF-SLO) for assessing diabetic retinopathy (DR) and diabetic macular oedema (DME) in a Chinese population, compared with clinical examination.MethodsThis is a retrospective cohort study. A series of 322 eyes from 164 patients with DM were included. Each patient underwent both dilated fundal examination with DR and DME grading by retina specialist and non-mydriatic 200° UWF-SLO (Daytona, Optos, Dunfermline, UK). The severity of DR and DME from UWF-SLO images was further graded by ophthalmologists, according to both international clinical DR and DME disease severity scales and the standard 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Any DR, DME and vision-threatening DR (VTDR) were treated as endpoints for this study.Results23 out of 322 images (7.14%), including all four cases with proliferative DR on clinical examinations, were determined as ungradable. When the international scale was used for grading UWF-SLO images, the sensitivity of any DR, DME and VTDR was 67.7%, 67.4% and 72.6%, respectively; the specificity of any DR, DME and VTDR was 97.8%, 97.3% and 97.8%, respectively. The agreement with clinical grading in picking up any DR, DME and VTDR was substantial, with κ-values of 0.634, 0.694 and 0.707, respectively. The performance of UWF-SLO was shown to be lower when ETDRS scale was used for grading the images.ConclusionThe performance of non-mydriatic UWF-SLO is comparable in identifying DR with that of clinical examination in a Chinese cohort. However, whether UWF-SLO can be considered as tool for screening DR is still undetermined.

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