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The Diabetic Retinopathy Clinical Research Network (DRCR.net) and Its Contributions to the Treatment of Diabetic Retinopathy.
Sun, JK, Jampol, LM
Ophthalmic research. 2019;(4):225-230
Abstract
Over the past two decades, the Diabetic Retinopathy Clinical Research Network (now known as the DRCR Retina Network) has contributed to multiple and substantial advances in the clinical care of diabetic eye disease. Network studies helped establish anti-vascular endothelial growth factor (VEGF) agents as an effective alternative to panretinal photocoagulation for eyes with proliferative diabetic retinopathy (PDR) and as first-line therapy for eyes with visual impairment for diabetic macular edema (DME), defined treatment algorithms for the use of intravitreal medications in these conditions, and provided critical data to understand how to better evaluate the diabetic eye using optical coherence tomography and other imaging modalities. Ongoing DRCR.net studies will address whether anti-VEGF therapy is effective at preventing vision-threatening complications in eyes with severe non-proliferative diabetic retinopathy, if photobiomodulation has a beneficial effect in eyes with DME, and whether initiation of DME treatment with bevacizumab and rescue with aflibercept can provide visual outcomes as good as those achieved with aflibercept alone. Future plans for the Network also include the expansion into non-diabetic eye disease in areas such as age-related macular degeneration.
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How do we evaluate the role of focal/grid photocoagulation in the treatment of diabetic macular edema?
Blindbaek, SL, Peto, T, Grauslund, J
Acta ophthalmologica. 2019;(4):339-346
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Vascular endothelial growth factor inhibitors (anti-VEGF) have consistently demonstrated efficacy and safety and changed both the aim and perspectives of diabetic macular edema (DME) treatment. Hence, the present and future role of focal/grid laser photocoagulation in DME treatment has been subjected to some debate. However, extensive insight into technical advances in novel laser systems, treatment protocols of anti-VEGF trials and the functional impact of modern focal/grid photocoagulation is needed to evaluate the present and future role of photocoagulation in DME treatment. Across a wide range of clinical trials laser therapy was required as adjunctive/rescue treatment in approximately 20-50% of patients receiving anti-VEGF monotherapy for centre involving DME. Further, a lower retreatment rate and a more stable reduction in retinal thickness have been demonstrated in more studies. However, lacking information on the laser systems used, their technical specifications and protocols of application often complicates direct comparison of results in anti-VEGF trials. Hence, this paper aimed to provide an overview of the currently available data relevant to the potential role of focal/grid laser photocoagulation in DME treatment including a thorough overview of the current most commonly used laser systems. Results with subthreshold diode micropulse laser photocoagulation are intriguing and may offer a valuable option as adjunctive therapy to anti-VEGF treatment. However, more well-designed studies on combination therapy are warranted to determine the full potential of modern retinal photocoagulation systems. In conclusion, current data suggest that focal/grid laser therapy should still be an option for consideration as adjunctive therapy in many patients.
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Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).
Li, Z, Zhang, Y, Liao, Y, Zeng, R, Zeng, P, Lan, Y
BMC ophthalmology. 2018;(1):19
Abstract
BACKGROUND Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP. METHODS A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic. RESULTS Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P = 0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P = 0.12). CONCLUSION This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.
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Diabetic macular edema: Evidence-based management.
Browning, DJ, Stewart, MW, Lee, C
Indian journal of ophthalmology. 2018;(12):1736-1750
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Diabetic macular edema (DME) is the most common cause of vision loss in patients with diabetic retinopathy with an increasing prevalence tied to the global epidemic in type 2 diabetes mellitus. Its pathophysiology starts with decreased retinal oxygen tension that manifests as retinal capillary hyperpermeability and increased intravascular pressure mediated by vascular endothelial growth factor (VEGF) upregulation and retinal vascular autoregulation, respectively. Spectral domain optical coherence tomography (SD-OCT) is the cornerstone of clinical assessment of DME. The foundation of treatment is metabolic control of hyperglycemia and blood pressure. Specific ophthalmic treatments include intravitreal anti-VEGF drug injections, intravitreal corticosteroid injections, focal laser photocoagulation, and vitrectomy, but a substantial fraction of eyes respond incompletely to all of these modalities resulting in visual loss and disordered retinal structure and vasculature visible on SD-OCT and OCT angiography. Efforts to close the gap between the results of interventions within randomized clinical trials and in real-world contexts, and to reduce the cost of care increasingly occupy innovation in the social organization of ophthalmic care of DME. Pharmacologic research is exploring other biochemical pathways involved in retinal vascular homeostasis that may provide new points of intervention effective in those cases unresponsive to current treatments.
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Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA).
Schmidt-Erfurth, U, Garcia-Arumi, J, Bandello, F, Berg, K, Chakravarthy, U, Gerendas, BS, Jonas, J, Larsen, M, Tadayoni, R, Loewenstein, A
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2017;(4):185-222
Abstract
Diabetic retinal disease is envisioned to become the plague of the coming decades with a steep increase of worldwide diabetes incidence followed by a substantial rise in retinal disease. Improvements in diagnostic and therapeutic care have to cope with this dilemma in a clinically and socioeconomically efficient manner. Laser treatment has found a less destructive competitor in pharmacological treatments. As a consequence of recent rigorous clinical trials, laser photocoagulation is no longer recommended for the treatment of diabetic macular edema (DME), and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids have maintained a role in the management of chronically persistent DME. The paradigm shifts in therapy are accompanied by a substantial break-through in diagnostics. The following guidance for the management of DME has been composed from the best updated knowledge of leading experts in Europe and represents another volume in the series of EURETINA recommendations for the management of retinal disease.
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A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders.
Scholz, P, Altay, L, Fauser, S
Advances in therapy. 2017;(7):1528-1555
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Micropulse laser treatment is an alternative to the conventional continuous-wave laser for the treatment of retinal or macular diseases. In contrast to the conventional laser, the therapeutic effect of the subthreshold micropulse laser is not accompanied by thermal retinal damage. This fact is of particular importance when a treatment near the fovea is required. Micropulse treatment is applied in indications such as central serous chorioretinopathy (CSC), diabetic macular edema (DME), or macular edema due to retinal vein occlusion (RVO). This review outlines and discusses the published literature of subthreshold micropulse laser treatment for CSC, DME, and macular edema after RVO.
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Proliferative diabetic retinopathy in typical retinitis pigmentosa.
Preethi, S, Rajalakshmi, AR
BMJ case reports. 2015
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A 39-year-old woman with typical retinitis pigmentosa (RP) for 9 years and a positive family history of night blindness was diagnosed with diabetes mellitus (DM). She developed proliferative diabetic retinopathy (PDR) during the course of disease. She was promptly managed with pan retinal photocoagulation (PRP). PDR developing in a case of typical RP is extremely rare and has not been reported in the literature to date. Recognition of this rare, vision threatening complication, points out a definite need to further look deep into the pathogenesis of diabetic retinopathy.
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Recent developments in laser treatment of diabetic retinopathy.
Yun, SH, Adelman, RA
Middle East African journal of ophthalmology. 2015;(2):157-63
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Laser photocoagulation has been the mainstay of diabetic retinopathy treatment since its development in mid-20(th) century. With the advent of antivascular endothelial growth factor therapy, the role of laser therapy appeared to be diminished, however many advances in laser technology have been developed since. This review will describe recent advances in laser treatment of diabetic retinopathy including pattern scan laser, short-pulse duration and a reduced fluence laser, and navigated laser system for proliferative diabetic retinopathy and macular edema.
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Recent developments in retinal lasers and delivery systems.
Yadav, NK, Jayadev, C, Rajendran, A, Nagpal, M
Indian journal of ophthalmology. 2014;(1):50-4
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Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has offered us newer lasing mediums, wavelengths and delivery systems. Pattern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical effect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more effective for vascular structures and offers a more uniform effect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.
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Laser photocoagulation for proliferative diabetic retinopathy.
Evans, JR, Michelessi, M, Virgili, G
The Cochrane database of systematic reviews. 2014;(11):CD011234
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BACKGROUND Diabetic retinopathy is a complication of diabetes in which high blood sugar levels damage the blood vessels in the retina. Sometimes new blood vessels grow in the retina, and these can have harmful effects; this is known as proliferative diabetic retinopathy. Laser photocoagulation is an intervention that is commonly used to treat diabetic retinopathy, in which light energy is applied to the retina with the aim of stopping the growth and development of new blood vessels, and thereby preserving vision. OBJECTIVES To assess the effects of laser photocoagulation for diabetic retinopathy compared to no treatment or deferred treatment. SEARCH METHODS We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 June 2014. SELECTION CRITERIA We included randomised controlled trials (RCTs) where people (or eyes) with diabetic retinopathy were randomly allocated to laser photocoagulation or no treatment or deferred treatment. We excluded trials of lasers that are no longer in routine use. Our primary outcome was the proportion of people who lost 15 or more letters (3 lines) of best-corrected visual acuity (BCVA) as measured on a logMAR chart at 12 months. We also looked at longer-term follow-up of the primary outcome at two to five years. Secondary outcomes included mean best corrected distance visual acuity, severe visual loss, mean near visual acuity, progression of diabetic retinopathy, quality of life, pain, loss of driving licence, vitreous haemorrhage and retinal detachment. DATA COLLECTION AND ANALYSIS We used standard methods as expected by the Cochrane Collaboration. Two review authors selected studies and extracted data. MAIN RESULTS We identified a large number of trials of laser photocoagulation of diabetic retinopathy (n = 83) but only five of these studies were eligible for inclusion in the review, i.e. they compared laser photocoagulation with currently available lasers to no (or deferred) treatment. Three studies were conducted in the USA, one study in the UK and one study in Japan. A total of 4786 people (9503 eyes) were included in these studies. The majority of participants in four of these trials were people with proliferative diabetic retinopathy; one trial recruited mainly people with non-proliferative retinopathy. Four of the studies evaluated panretinal photocoagulation with argon laser and one study investigated selective photocoagulation of non-perfusion areas. Three studies compared laser treatment to no treatment and two studies compared laser treatment to deferred laser treatment. All studies were at risk of performance bias because the treatment and control were different and no study attempted to produce a sham treatment. Three studies were considered to be at risk of attrition bias.At 12 months there was little difference between eyes that received laser photocoagulation and those allocated to no treatment (or deferred treatment), in terms of loss of 15 or more letters of visual acuity (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.89 to 1.11; 8926 eyes; 2 RCTs, low quality evidence). Longer term follow-up did not show a consistent pattern, but one study found a 20% reduction in risk of loss of 15 or more letters of visual acuity at five years with laser treatment. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months (RR 0.46, 95% CI 0.24 to 0.86; 9276 eyes; 4 RCTs, moderate quality evidence). There was a beneficial effect on progression of diabetic retinopathy with treated eyes experiencing a 50% reduction in risk of progression of diabetic retinopathy (RR 0.49, 95% CI 0.37 to 0.64; 8331 eyes; 4 RCTs, low quality evidence) and a similar reduction in risk of vitreous haemorrhage (RR 0.56, 95% CI 0.37 to 0.85; 224 eyes; 2 RCTs, low quality evidence).None of the studies reported near visual acuity or patient-relevant outcomes such as quality of life, pain, loss of driving licence or adverse effects such as retinal detachment.We did not plan any subgroup analyses, but there was a difference in baseline risk in participants with non-proliferative retinopathy compared to those with proliferative retinopathy. With the small number of included studies we could not do a formal subgroup analysis comparing effect in proliferative and non-proliferative retinopathy. AUTHORS' CONCLUSIONS This review provides evidence that laser photocoagulation is beneficial in treating proliferative diabetic retinopathy. We judged the evidence to be moderate or low, depending on the outcome. This is partly related to reporting of trials conducted many years ago, after which panretinal photocoagulation has become the mainstay of treatment of proliferative diabetic retinopathy.Future Cochrane Reviews on variations in the laser treatment protocol are planned. Future research on laser photocoagulation should investigate the combination of laser photocoagulation with newer treatments such as anti-vascular endothelial growth factors (anti-VEGFs).