Corticosteroid Use for Diabetic Macular Edema: Old Fad or New Trend?

Diabetic retinopathy is the leading cause of blindness in working age individuals in developed countries. Most cases of diabetes related vision loss result from breakdown of the blood-retinal barrier with resultant diabetic macular edema (DME). For over 30 years, laser photocoagulation has been the standard therapy for DME, but most eyes do not experience significant improvements in visual acuity. Intravitreal injections of drugs that inhibit the action of vascular endothelial growth factor (VEGF) lead to gains in vision, but can be expensive and need to be repeated frequently. In addition to VEGF-mediated breakdown of the blood-retinal barrier, recent evidence suggests that inflammation plays an important role in the development of DME. Recognizing this, physicians have injected steroids into the vitreous and developers have created sustained release implants. Intravitreal injections of triamcinolone acetonide lead to rapid resolution of macular edema and significant short-term improvements in visual acuity, but unfortunately, visual acuities diminish when treatment is continued through 2 years. However, intravitreal triamcinolone remains an attractive treatment option for eyes that are pseudophakic, scheduled to undergo cataract surgery, resistant to laser photocoagulation, or require urgent panretinal photocoagulation for proliferative retinopathy. In controlled trials, intraocular implants that slowly release dexamethasone and fluocinolone show promise in reducing macular edema and improving visual acuity. The high incidences of drug related cataracts and glaucoma, however, require that corticosteroids be used cautiously and that patients be selected carefully. The increasing number of patients with DME, the burgeoning cost of medical care and the continuing development of intravitreal steroids suggest that the use of these agents will likely increase in coming years.     

Intravitreal steroid versus macular laser for treatment of diabetic macular edema

Diabetic macular edema is a leading cause of vision loss in the United States. Focal/grid laser photocoagulation has been the gold standard for treatment over the past two decades. Intravitreal pharmacologic treatments increasingly have been used over the past 5 years. Various studies have shown the possible benefits of intravitreal corticosteroids and anti-vascular endothelial growth factors in the treatment of diabetic macular edema. However, focal/grid laser photocoagulation continues to be the only proven safe and effective treatment for diabetic macular edema.     

Diabetes und Auge

Diabetic retinopathy is the most common cause of blindness in the working age population in industrialized nations and the most frequent microvascular complication of diabetes mellitus. Due to the expected increase in patients suffering from diabetes worldwide, the number of patients in need of regular ophthalmological examinations and therapeutic interventions is also expected to rise. Therefore, optimized screening programs under optimal use of available resources of the ophthalmological infrastructure will become even more important. Diabetic macular edema and proliferative diabetic retinopathy are the main reasons for visual loss in these patients. Adequate control of blood glucose and blood pressure levels can significantly reduce the incidence or progression of sight-threatening diabetic retinopathy. Regular ophthalmological examinations and timely laser photocoagulation in cases of clinically significant diabetic macular edema or early proliferative diabetic retinopathy can drastically reduce the risk of blindness. Additionally, intravitreal drug injections and pars plana vitrectomy have recently become available for treatment in advanced stages of the disease.     

Vascular Endothelial Growth Factor Inhibitors for Diabetic Retinopathy

The prevalence of diabetes is growing at epidemic rates in the USA. Diabetic retinopathy develops in a large proportion of patients and is a leading cause of blindness worldwide. Systemic management of diabetic retinopathy has included glycemic, hypertension, and lipid control. Local ophthalmic treatment in the form of focal/grid or panretinal laser photocoagulation has been shown to prevent vision loss in diabetic edema and proliferative diabetic retinopathy, respectively. The introduction of anti-vascular endothelial growth factor for diabetic macular edema and retinopathy has provided clinicians with improved clinical outcomes with potentially less damaging effects than laser.     

Difference in the efficacy of intravitreal dexamethasone implant before and after silicone oil removal: A case report

Rationale:An intravitreal dexamethasone (IV-DEX) implant is safe and effective for the treatment of macular edemas; however, the efficacy of IV-DEX implants in silicone oil (SO)-filled eyes remains controversial. There is no previous study comparing an IV-DEX implant in the same eye with and without intravitreal SO.Patient concerns:A 72-year-old man with proliferative diabetic retinopathy, macular edema, and rhegmatogenous retinal detachment, treated with pars plana vitrectomy with SO tamponade had refractory macular edema.Diagnosis:Refractory macular edema.Intervention:Subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation were performed; this was followed by intravitreal SO removal combined with IV-DEX implantation.Outcomes:The macular edema did not decrease significantly with posterior subtenon triamcinolone injection, intravitreal anti-vascular endothelial growth factor injection, and IV-DEX implantation; however, the edema was relieved after SO removal and a new IV-DEX implantation.Lessons:IV-DEX implant may be less efficacious in the treatment of macular edema in an SO-filled eye than that in a normal vitreous cavity.     

Diabetische Retinopathie

Diabetic retinopathy is a microvascular complication of diabetes, which can be found in almost all diabetic patients in the course of the disease. It is the most common cause of blindness in the western world in working age patients. The main reasons for loss of diabetic macular edema, which can occur at any stage of the disease and proliferative diabetic retinopathy. Risk factors are the duration of disease and poorly controlled arterial hypertension and blood glucose levels. Regular ophthalmologic surveillance is essential even in asymptomatic patients in order to prevent long-term consequences. The therapeutic options are laser photocoagulation, vitrectomy and the newly available intravitreal application of drugs.     

Posterior subtenon and intravitreal triamcinolone acetonide for diabetic macular edema

AIM: To evaluate retroprospectively the clinical consequences of posterior subtenon (PSTT) and intravitreal (IVT) triamcinolone acetonide injections in diabetic macular edema (DME) refractory to conventional grid laser photocoagulation. MATERIAL AND METHODS: Eyes with clinically significant DME refractory to grid laser photocoagulation were assessed for the inclusion in the study. Complete ophthalmic examination with fluorescein angiography (FA) and optic coherence tomography (OCT) were performed before and in the 1st, 3rd, and 6th months of the treatment. The IVT group received 4 mg/0.1 ml and the PSTT group received 20 mg/0.5 ml triamcinolone injection. PSTT but not IVT injection was repeated in case of recurrent edema. IVT was also applied to the eyes with resistant macular edema after PSTT injection (secondary IVT group). RESULTS: There were 85 eyes of 60 patients in the PSTT group and 41 eyes of 35 patients in IVT group. There were 24 eyes in the primary IVT group and 17 eyes in the secondary IVT group. Mean follow-up time was 4.1+/-1.9 and 4.6+/-2.2 months after PSTT and IVT injections, respectively. In the PSTT group, the mean visual acuity increased from 0.19+/-0.18 to 0.22+/-0.19 and the mean central foveal thickness decreased from 413.1+/-117.5 to 312.1+/-103.1 microm (P=.001 and P=.0001, respectively) during the first 3 months. In the IVT group, the mean visual acuity and central foveal thickness were found to be 0.15+/-0.14 and 494.5+/-141.3 microm before the treatment and 0.20+/-0.16 and 288.4+/-88.5 microm 3 months after the treatment, respectively (P=.008 and P=.001, respectively). The effect in central foveal thickness was significantly greater in the primary IVT group than in the PSTT group (P=.002). There was no significant difference with respect to the decrease in the central foveal thickness and increase in visual acuity between the primary and secondary IVT injections (Mann-Whitney U test, P>.05). The steroid effect started to diminish after the 3rd month. The recurrence of macular edema was seen in 7.1% in the PSTT group starting after 3 months. Twenty percent of the eyes in the PSTT group did not respond to the treatment at all and had secondary IVT injections. Significant intraocular pressure increase was found in 8.2% of the PSTT group and in 24.3% of IVT injection. There was one case of pseudomonas endophthalmitis in the IVT group. CONCLUSION: This study is the first study comparing the clinical outcomes of PSTT and IVT injections for the treatment of DME. Both PSTT and IVT injections caused a significant increase in visual acuity and a decrease in central foveal thickness, especially in the short term. The effect was more pronounced in the IVT group; however, PSTT injection also seemed to be a safe and effective technique for the treatment of DME. Further prospective studies are warranted to assess the efficacy and side effects of IVT and PSTT injections for the treatment of DME.     

Intravitreal triamcinolone acetonide for patients with macular edema due to branch retinal vein occlusion

We designed a case series study to evaluate the outcome of intravitreal triamcinolone acetonide for the treatment of macular edema due to branch retinal vein occlusion (BRVO). The prospective comparative nonrandomized clinical interventional study included 27 patients (27 eyes) with macular edema due to BRVO. The study group consisted of 16 patients who had accepted an intravitreal injection (IVI) of 4 mg triamcinolone acetonide. The control group included 11 patients without IVI of triamcinolone acetonide. The mean follow-up was 103.00 +/- 36.24 days in the study group and 94.55 +/- 36.31 days in the control group. In the study group, visual acuity measurements improved significantly (p < 0.001) from 0.77 +/- 0.43 logarithm of minimal angle of resolution (logMAR) preoperatively to a best postoperative visual acuity of 0.44 +/- 0.43 logMAR. Fourteen eyes (87.5%) gained improvement in visual acuity, with 10 eyes (62.5%) showing an increase in visual acuity of at least two Snellen lines. All 16 patients showed significant macular edema resolution in optical coherence tomography examination (p < 0.001) and perivascular leakage decrease in fluorescein angiography post-IVI. In the control group, baseline best-corrected visual acuity and best-corrected visual acuity during the follow-up did not vary significantly (p = 0.294). In conclusion, IVI of triamcinolone acetonide can lead to an increase in visual acuity and a resolution of macular edema in patients with BRVO.     

The laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion: A protocol for systematic review and meta-analysis

Background:At present, laser is regarded as an effective treatment for macular edema secondary to branch retinal vein occlusion. With the breakthrough of anti-vascular endothelial growth factor drugs in ophthalmology clinical research, the intravitreal injection of ranibizumab is widely applied, but both methods have their limitations, so some clinical studies have combined and applied them together. However, the clinical results are inconsistent and controversial, and there is no relevant system evaluation for the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion now.Objective:Meta analysis is used to analyze and evaluate the effectiveness and safety of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion.Method:CNKI, VIP, WANFANG, China Biology Medicine disc, Web of Science, PubMed, Embase, Cochrane Library have used random controlled clinical trial of laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion from the establishment of the database to October 2020. Two researchers conducted independent screening, quality assessment and data extraction for the literatures, and used RevMan5.3 to conduct Meta analysis for the included literatures.Result:The research has evaluated the effectiveness and safety of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion through the aspects of the best corrected visual acuity 6 months after operation, macular center thickness and the incidence of adverse reactions such as elevated intraocular pressure, endophthalmitis, vitreous hemorrhage and cataract.Conclusion:Laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion has good effect, and the research has provided reliable evidence for the use of clinical treatment of the laser combined with intravitreal injection of ranibizumab for treatment of macular edema secondary to branch retinal vein occlusion.     

玻璃体注药联合激光光凝治疗糖尿病视网膜病变的临床疗效

目的 研究玻璃体注药联合激光光凝治疗糖尿病视网膜病变的临床疗效.方法 选取2019年1月—2020年9月在该院确诊的糖尿病视网膜病变患者,根据治疗方案不同分为两组,观察组(玻璃体注药联合激光光凝)和对照组(单纯激光光凝),对比两组患者的治疗疗效.结果 对照组治疗前视力为(0.24±0.12),治疗后视力为(0.43±0...     

Medikamentöse Therapie der diabetischen Retinopathie und Makulopathie

Although the prognosis in diabetic eye complications has improved as a result of better glycemic and blood pressure control as well as advances in the established therapy options of laser coagulation and vitreoretinal surgery, diabetic retinopathy remains the most common cause of blindness among the working population of the industrial nations. Experimental and clinical data indicate that new pharmacological options for pathophysiologically oriented therapy may be effective. Initial experience with intravitreal injection of the glucocorticoid triamcinolone acetonide or vascular endothelial growth factor (VEGF) inhibitors pegaptanib, ranibizumab and bevacizumab have shown that, in the case of diffuse diabetic macular edema, which has been difficult to treat to date, at least a temporary anatomic and partly functional improvement can be achieved. Furthermore, the application of these intravitreal therapy modalities as adjuvants to/after laser coagulation or surgery can be considered in selected cases of focal diabetic macular edema and proliferative diabetic retinopathy. Further prospective trials are needed to answer questions on duration of effect, the need for repeat injections, as well as on side effects.     

Anti-vascular endothelial growth factor drug treatment of diabetic macular edema: the evolution continues

Diabetic mellitus is the leading cause of blindness in working aged patients in developing nations. Due to the buildup of abnormal metabolites from several overactive biochemical pathways, chronic hyperglycemia causes oxidative stress in the retina which upregulates vascular endothelial growth factor (VEGF). Together with other growth factors and metabolites, VEGF causes endothelial cell proliferation, vasodilation, recruitment of inflammatory cells, and increased vascular permeability, leading to breakdown of the blood-retinal barrier. This allows trans-cellular exudation into the interstitial space resulting in diabetic macular edema (DME). For over 3 decades the standard treatment for DME has been laser photocoagulation. Though laser reduces the incidence of vision loss by 50%, few eyes with diffuse edema experience improved vision. This has led physicians to use the VEGF-binding drugs pegaptanib, ranibizumab, and aflibercept, each of which has been approved for the treatment of exudative macular degeneration, and bevacizumab which is commonly used off-label for a variety of chorioretinal disorders. Intravitreal administration of each drug frequently causes rapid improvement of DME with sustained improvement in vision through 2 years. Though these drugs significantly outperform laser photocoagulation over treatment periods of 1 year of less, the advantages appear to lessen when trials approach 2 years. Further studies to better determine relative efficacies of anti-VEGF drugs and laser photocoagulation are continuing.     

Antisense Oligonucleotide Therapy in Diabetic Retinopathy

Diabetic retinopathy is one of the leading causes of blindness in the United States and other parts of the world. Historically, laser photocoagulation and vitrectomy surgery have been used for the treatment of diabetic retinopathy, including diabetic macular edema. Both procedures have proven to be useful under certain conditions but have their limitations. New pathways and processes that promote diabetic retinopathy have been identified, and several new therapeutic approaches are under investigation. These new therapies may be beneficial in the treatment of diabetic retinopathy and include antivascular endothelial growth factor agents, corticosteroids, and therapies that may potentially target a number of additional diabetic retinopathy-related factors and processes, including antisense oligonucleotides. Second-generation antisense oligonucleotides, such as iCo-007, may offer a significant advantage in the treatment of diabetic retinopathy by downregulating the signal pathways of multiple growth factors that seem to play a critical role in the process of ocular angiogenesis and vascular leakage. Benefits of such molecules are expected to include the specificity of the kinase target and an extended half-life, resulting in less frequent intravitreal drug administration, resistance to molecule degradation, and a good safety profile.     

改良糖尿病视网膜病变早期治疗研究组格栅样光凝与轻度黄斑格栅样光凝在治疗糖尿病黄斑水肿中的疗效比较

目的比较改良糖尿病视网膜病变早期治疗研究组（ETDRS）格栅样光凝及轻度格栅样光凝在糖尿病视网膜病变黄斑水肿治疗中的疗效。方法选取2008年1月至2010年1月于我院眼科门诊就诊及内分泌科会诊的伴有糖尿病黄斑水肿（DME）的轻至中度非增殖性糖尿病视网膜病变（NPDR）患者为研究对象,共72例97眼,其中男40例55眼、女32例42眼。入选患者均进行全面眼科检查,采用随机化分组表将患者分为改良ETDRS格栅样光凝组（36例48眼）及轻度格栅样光凝组（36例49眼）进行激光治疗,治疗后随访24个月。观察2组患者治疗前后视力、黄斑中心凹视网膜厚度等变化情况,数据采用SPSS16．0软件进行统计分析。统计学方法采用One．wayANOVA检验,两两比较采用t检验。结果改良ETDRS格栅样光凝组和轻度格栅样光凝组患者治疗后24个月均可见视力明显提高,与治疗前比较差异具有统计学意义（改良ETDRS格栅样光凝组：初始值55．4-21,治疗24个月后59±21;轻度格栅样光凝组：初始值544-11,治疗24个月后584-13,均P〈0．05）,但2组患者视力改善程度在各随访时间点差异均无统计学意义（P〉0．05）。改良ETDRS光凝组和轻度格栅样光凝组患者治疗后24个月内黄斑中心凹视网膜厚度均有所下降,与治疗前比较差异具有统计学意义（改良ETDRS格栅样光凝组：初始值395±174,治疗24个月后2044-16;轻度格栅样光凝组：初始值464±204,治疗24个月后2414-13,均P〈0．05）。但2组在各时间截点黄斑中心凹视网膜厚度改变差异均无统计学意义（均P〉0．05）。结论对轻、中度NPDR合并DME患者采用改良ETDRS光凝或轻度格栅样光凝治疗并随访24个月后发现2种光凝方法均在改善黄斑水肿患者远期视力方面具有一定疗效且无明显差异。     

Diabetic retinopathy: current and new treatment options

Diabetes mellitus has become a major health concern worldwide and its incidence is projected to increase. Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are considered the most sight-threatening ocular complications in these patients. Pivotal studies, such as the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetic Retinopathy Study (DRS), have established macular and pan-retinal laser as the gold-standard of treatment for these complications. The recent discovery of the vascular endothelial growth factor (VEGF) and its role in the development of proliferative disease, has led to a movement towards treating PDR and DME with anti-angiogenic medications alone or in conjunction with the gold-standard of care. Due to the severity of the diabetic ocular complications and the rising incidence of diabetes worldwide, it is important for the non-ophthalmologist care provider to be informed of the new treatments available for these conditions in an effort to better guide their patients. In this review, I will discuss the importance of these new methods of treatment as well as the significance of systemic glucose control, vitreous surgery and laser photocoagulation.     

Comparison of intravitreal injection of bevacizumab and triamcinolone acetonide in the treatment of uveitic macular edema

Background: Cystoid Macular Edema (CME) is one of the most common and sight threatening complications of uveitis. Intravitreal injection of corticosteroids and Anti-VEGF are two routine options for treatment. Objective: To compare the effects of intravitreal injections of Bevacizumab and Triamcinolone Acetonide for the treatment of persistent macular edema in non-infectious uveitis. Methods: In a randomized clinical trial, sixty eyes of 55 patients were enrolled in the study. Patients were divided into two groups with randomized digits table. 29 eyes received 4 mg of intravitreal triamcinolone acetonide, and 31 eyes received 1.25 mg of intravitreal bevacizumab. Two main outcome measures were changes in visual acuity, measured with logarithm of minimal angle of resolution, and central macular thickness, measured with optical coherence tomography. Results: The mean follow-up was 25.3 weeks. The best visual acuities were achieved 6 months after injection in both groups. Improvement in visual acuity at 6 months was achieved in 28/29 (96%) of eyes in Triamcinolone group and in 26/31 (83%) eyes in Bevacizumab group (p=0.196). None of the eyes showed worsening of visual acuity after 6 months. Mean of central macular thickness in the pre-injection time for intravitreal triamcinolone acetonide (IVTA) group was 295.62 μ, and 309.87 μ in intravitreal bevacizumab (IVB) group, which were decreased after six months to 199.27 μ and 221.06 μ, respectively (p<0.001). Conclusion: This study shows that IVT and IVB are both effective in improving vision in uveitic CME. Although effects of triamcinolone on Central Macular Thickness (CMT) are more apparent, this superiority is not seen on Best Corrected Visual Acuity (BCVA).     

微脉冲激光或传统格栅光凝联合康柏西普治疗糖尿病黄斑水肿的临床分析

目的观察微脉冲激光或传统格栅光凝联合康柏西普治疗糖尿病黄斑水肿(DME)的有效性、安全性。方法纳入2017年1月—2019年6月DME患者98眼,577 nm阈值下微脉冲联合治疗(A组)32眼、传统格栅光凝联合治疗(B组)30只眼、单纯康柏西普治疗(C组)36眼。观察最佳矫正视力(BCVA)、黄斑中心凹厚度(CFT)、黄斑容积(MV)及视网膜的微结构变化及注射针数。结果所有患者治疗后3、6、9、12个月的BCVA、CFT、MV均较前改善,差异有统计学意义(F=39.558、62.901、10.078,P<0.001)。组间比较差异无统计学意义(F=0.417、0.085、0.061,P=0.513、0.675、0.823)。A、B组年平均药物注射次数分别为(6.3±0.9)、(6.5±1.1)次低于C组(8.6±2.2)次,差异有统计学意义(F=7.980,P<0.05)。B组可见激光损伤而A组未见。结论激光联合治疗与单纯药物治疗均对DME有效,联合治疗可减少药物注射次数;微脉冲激光较传统格栅光凝更安全。     

Treatment of diabetic retinopathy with laser photocoagulation (author's transl)]

Laser photocoagulation has changed the visual prognosis of diabetic patients affected by retinopathy. It aims to lower the risk of blindness of diabetic patients. The goal of photocoagulation is to reduce the tissue damage of microangiopathic origin expressed by nonperfusion areas and permeability abnormalities that are responsible for retinal ischemia and oedema respectively. Loss of visual acuity in the diabetic is due mainly to two causes : first, vitreous hemorrhage with its dramatic loss of vision; secondly, macular cystoid oedema, occuring more commonly and with progressive loss of central vision. The efficiency of pan-retinal photocoagulation in reducing the risk of vitreous hemorrhage and consequent blindness in patients with disc or preretinal newly formed vessels, has been ascertained by American and British randomised studies. The indications, technics and results of photocoagulation in non-proliferative diabetic retinopathy are the subject of many studies. Only photocoagulation for macular oedema due to intra-retinal microvascular abnormality has shown to be of benefit.     

Aggravated capillary non-perfusion after intravitreal bevacizumab for macular edema secondary to systemic lupus erythematosus and anti-phospholipid syndrome

A 22-year-old female with history of systemic lupus erythematosus (SLE) was referred for evaluation of decreased visual acuity in her right eye. Her best-corrected visual acuity (BCVA) at the time of presentation was 20/160. Widespread cotton wool spots and macular edema were seen on biomicroscopy. Fluorescein angiography (FA) revealed retinal arterial and venous obstruction with capillary nonperfusion at the superotemporal retina. Antiphospholipid syndrome (APS) was diagnosed based on positive lupus anti-coagulant and ocular manifestations. Scattered laser photocoagulation was applied at the nonperfusion area but the visual acuity continued to deteriorate due to macular edema. Intravitreal bevacizumab (IVB) was administered for macular edema. One day after IVB, the BCVA decreased to count fingers. FA revealed extended non-perfusion from the superotemporal area to the posterior pole. Use of intravitreal bevacizumab for macular edema secondary to SLE or APS should be considered carefully and patients monitored closely for vascular complications.