scholarly journals Intravitreal Anti-Vascular Endothelial Growth Factor Agents for the Treatment of Diabetic Retinopathy: A Review of the Literature

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1137
Author(s):  
Irini Chatziralli ◽  
Anat Loewenstein
Keyword(s):  
Diabetic Retinopathy ◽  
Vitreous Hemorrhage ◽  
Fundus Photography ◽  
Panretinal Photocoagulation ◽  
Wide Field ◽  
Vascular Endothelial ◽  
Keywords Diabetic Retinopathy ◽  
Anti Vegf ◽  
The Impact

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. The purpose of this review is to gather the existing literature regarding the use of the approved anti-vascular endothelial growth (anti-VEGF) agents in the treatment of DR. Methods: A comprehensive literature review in PubMed engine search was performed for articles written in English language up to 1 July 2021, using the keywords “diabetic retinopathy”, “ranibizumab”, “aflibercept”, and “anti-VEGF”. Emphasis was given on pivotal trials and recent robust studies. Results: Intravitreal anti-VEGF agents have been found to significantly improve visual acuity and reduce retinal thickness in patients with diabetic macular edema (DME) in a long-term follow-up ranging from 1 to 5 years and are considered the standard-of-care in such patients. Regarding DR, intravitreal anti-VEGF agents provided ≥2-step improvement in DR severity on color fundus photography in about 30–35% of patients with NPDR at baseline, in the majority of clinical trials originally designed to evaluate the efficacy of intravitreal anti-VEGF agents in patients with DME. Protocol S and CLARITY study have firstly reported that intravitreal anti-VEGF agents are non-inferior to panretinal photocoagulation (PRP) in patients with proliferative DR (PDR). However, the use of new imaging modalities, such as optical coherence tomography-angiography and wide-field fluorescein angiography, reveals conflicting results about the impact of anti-VEGF agents on the regression of retinal non-perfusion in patients with DR. Furthermore, one should consider the high “loss to follow-up” rate and its devastating consequences especially in patients with PDR, when deciding to treat the latter with intravitreal anti-VEGF agents alone compared to PRP. In patients with PDR, combination of treatment of intravitreal anti-VEGF agents and PRP has been also supported. Moreover, in the specific case of vitreous hemorrhage or tractional retinal detachment as complications of PDR, intravitreal anti-VEGF agents have been found to be beneficial as an adjunct to pars plana vitrectomy (PPV), most commonly given 3–7 days before PPV, offering reduction in the recurrence of vitreous hemorrhage. Conclusions: There is no general consensus regarding the use of intravitreal anti-VEGF agents in patients with DR. Although anti-VEGF agents are the gold standard in the treatment of DME and seem to improve DR severity, challenges in their use exist and should be taken into account in the decision of treatment, based on an individualized approach.

Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL)

2018 ◽  
Vol 2 (3) ◽  
pp. 127-137
Author(s):  
Dennis M. Marcus ◽  
Harinderjit Singh ◽  
Davis C. Starnes ◽  
Harveen Walia ◽  
Amina Farooq ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Hemorrhage ◽  
Panretinal Photocoagulation ◽  
Short Term ◽  
Safety And Efficacy ◽  
Intravitreal Aflibercept ◽  
Central Subfield Thickness ◽  
Endothelial Growth Factor

Purpose: For proliferative diabetic retinopathy (PDR) eyes not requiring vitrectomy, Diabetic Retinopathy Clinical Research Protocol S and the CLARITY trial demonstrated better visual function and anatomical outcomes with less proliferative and diabetic macular edema consequences in the antivascular endothelial growth factor groups compared to the panretinal photocoagulation groups. Intravitreal aflibercept injection (IAI) may represent a useful therapy with vitrectomy for PDR-related vitreous hemorrhage (VH) as a viable alternative to intraoperative endolaser during vitrectomy. We will determine the safety and efficacy when aflibercept is used for PDR-related VH with endolaserless vitrectomy. Methods: Evaluation of endolaserless vitrectomy and 2 mg IAI for PDR-related VH. Eyes receive 1 preoperative and intraoperative IAI followed by randomization to a q8week group receiving 4 postoperative q4week IAI followed by q8week IAI or q16week group receiving 2 postoperative q4week IAI followed by q16week IAI. Main Outcome Measures: Herein, we present pooled safety and efficacy outcomes through 4 months. Results: Twenty-one of 24 eyes were randomized. Preoperative average visual acuity (VA) was 36 letters (20/200). At 4-month follow-up, 18 of 21 randomized eyes showed an average VA of 72 letters (20/40) with an average visual gain of 38 (range, 0-84 gain) letters. Average optical coherence tomography (OCT) central subfield thickness (CST) at 1-month postoperative follow-up was 311 µm. Average OCT CST at 4-month follow-up was 272 µm (average thinning of 38 µm). No significant short-term ocular or systemic adverse events were observed through 4 months. Conclusions: Endolaserless vitrectomy with IAI for PDR-related VH demonstrates short-term safety with significant VA improvement.

scholarly journals Incidence and Risk Factors for Tractional Macular Detachment after Anti-Vascular Endothelial Growth Factor Agent Pretreatment before Vitrectomy for Complicated Proliferative Diabetic Retinopathy

2019 ◽  
Vol 8 (11) ◽  
pp. 1960
Author(s):  
Andrea Russo ◽  
Antonio Longo ◽  
Teresio Avitabile ◽  
Vincenza Bonfiglio ◽  
Matteo Fallico ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Hemorrhage ◽  
Vascular Endothelial ◽  
Macular Detachment ◽  
Anti Vegf ◽  
Endothelial Growth Factor

The study’s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65–0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11–0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02–1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.

scholarly journals Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy

2021 ◽  
Vol 10 (20) ◽  
pp. 4666
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Kazuo Tsubota ◽  
Kazuno Negishi ◽  
Toshihide Kurihara
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Vascular Endothelial Cells ◽  
Vitreous Hemorrhage ◽  
Diabetic Animal ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Anti Vegf

Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments.

Loss to Follow-Up in Patients with Proliferative Diabetic Retinopathy after Panretinal Photocoagulation or Intravitreal Anti-VEGF Injections

Ophthalmology ◽  
2018 ◽  
Vol 125 (9) ◽  
pp. 1386-1392 ◽  
Author(s):  
Anthony Obeid ◽  
Xinxiao Gao ◽  
Ferhina S. Ali ◽  
Katherine E. Talcott ◽  
Christopher M. Aderman ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Panretinal Photocoagulation ◽  
Loss To Follow Up ◽  
Anti Vegf

scholarly journals Retinal arteriolar calibre and venular fractal dimension predict progression of proliferative diabetic retinopathy 6 months after panretinal photocoagulation: a prospective, clinical interventional study

2021 ◽  
Vol 6 (1) ◽  
pp. e000661
Author(s):  
Thomas Lee Torp ◽  
Ryo Kawasaki ◽  
Tien Yin Wong ◽  
Tunde Peto ◽  
Jakob Grauslund
Keyword(s):  
Diabetic Retinopathy ◽  
Fractal Dimension ◽  
Prospective Study ◽  
Disease Activity ◽  
Proliferative Diabetic Retinopathy ◽  
Panretinal Photocoagulation ◽  
Wide Field ◽  
Treatment Naïve ◽  
Retinal Arteriolar

ObjectiveWe examined the hypothesis that baseline retinal vascular geometry in patients with proliferative diabetic retinopathy (PDR) predicts disease activity 6 months after panretinal photocoagulation (PRP).Methods and analysisWe included 47 eyes from 40 patients with treatment-naïve PDR in a 6-month prospective study. Diagnosis of PDR and disease activity was evaluated by wide-field fluorescein angiography (Optomap, Optos, Dunfermline, Scotland, UK). At baseline and 6-month follow-up, the retinal vessel geometry was measured on optic disc centred images using semiautomated software Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE, Dundee, Scotland).ResultsAt baseline, mean age and duration of diabetes was 51.6 and 21.4 years, and 62.5% were men. Seventeen eyes (36.2%) had progression of PDR during follow-up. At baseline, we found higher retinal arteriolar calibre (31.3±0.8 vs 28.8±0.8 pixels, p=0.02) and venous fractal dimension (FD) (1.257±0.011 vs 1.222±0.011, p=0.02) in eyes with progression of PDR as compared with eyes with non-progression. In a multiple logistic regression model, both higher retinal arteriolar calibre (OR 1.34, 95% CI, 1.09 to 1.64, p<0.01) and venular FD (OR 1.15, 95% CI, 1.04 to 1.27, p<0.01) predicted progression of PDR. Venular calibre was seen to increase from baseline to month six regardless of disease progression (non-progression 45.0±0.7 vs 52.7±1.8 pixels, p<0.01; progression 46.2±0.8 vs 51.0±1.7 pixels, p<0.01).ConclusionOur prospective study showed that arteriolar calibre and venular FD at baseline were predictive of disease activity 6 months after PRP treatment in patients with treatment-naïve PDR.

scholarly journals Outcomes of 23-Gauge Vitrectomy Combined with Phacoemulsification, Panretinal Photocoagulation, and Trabeculectomy without Use of Anti-VEGF Agents for Neovascular Glaucoma with Vitreous Hemorrhage

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Hua Yan
Keyword(s):  
Vitreous Hemorrhage ◽  
Neovascular Glaucoma ◽  
Panretinal Photocoagulation ◽  
Light Perception ◽  
Anti Vegf ◽  
The Mean ◽  
23 Gauge ◽  
One Year ◽  
Time Point

Purpose. To evaluate the outcomes of 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti-VEGF-agents for NVG. Methods. Eighteen eyes of 18 patients with NVG underwent 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti-VEGF agents. The preoperative BCVA ranged from light perception to 0.2. The preoperative IOP ranged from 38 mmHg to 64 mmHg with a mean of 54±8 mmHg. The average follow-up time was 14.5±3 months with a range from 11 to 24 months. Results. The postoperative VA increased in 14 eyes and was stable in 4 eyes at the final follow-up. The mean IOP was 12±3 mmHg at postoperative day 1. The mean IOP was 15±2 mmHg, 16±3 mmHg, 23±5 mmHg, 28±4 mmHg, 22±5 mmHg, 17±3 mmHg, and 19±4 mmHg at postoperative days 2 and 3, 1, 2, 3, and 12 weeks, and 1 year postoperatively, respectively, with a range from 10 to 30 mmHg at the final follow-up time point of one year. The IOP was significantly lower than the preoperative one 12 weeks postoperatively (p<0.05). Conclusion. 23-gauge vitrectomy combined with phacoemulsification, PRP, and trabeculectomy without use of anti-VEGF-agents is a safe and effective method in treating NVG.

scholarly journals The U-Shaped Association between Bilirubin and Diabetic Retinopathy Risk: A Five-Year Cohort Based on 5323 Male Diabetic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Miao Liu ◽  
Jianhua Wang ◽  
Yao He
Keyword(s):  
Diabetic Retinopathy ◽  
Cohort Study ◽  
Risk Model ◽  
Continuous Variable ◽  
Hazard Ratio ◽  
Diabetic Patients ◽  
Lower Baseline ◽  
The Impact ◽  
Chinese Male

Aims. This study aimed at assessing the impact of baseline bilirubin (TBiL) on the incidence of diabetic retinopathy (DR) based on a five-year cohort study which consisted of 5323 Chinese male diabetic patients.Methods. A cohort study based on 5323 male diabetic patients was conducted in Beijing, from 2009 to 2013. Both baseline TBiL and follow-up changes were measured. Cox proportional risk model was used to calculate the hazard ratio (HR) of TBiL for DR risk.Results. During the follow-up period, there were 269 new DR cases. The incidence of five-year follow-up was 5.1% (95% CI: 4.5%~5.6%). The TBiL level of those who had diabetic retinopathy was lower than that of those without (12.51+ 1.20 mol/L and 13.11+ 1.32μmol/L,P=0.033). And more interestingly, along with the quintiles of baseline TBiL, there showed a U-shaped curve with DR incidence. And the RRs were 0.928 (95% CI: 0.646–1.331), 0.544 (95% CI: 0.365–0.811), 0.913 (95% CI: 0.629–1.324), and 1.035 (95% CI: 0.725–1.479) for the second, third, fourth, and fifth quintiles of baseline TBiL levels, respectively, compared with the first quintile. For follow-up TBiL changes, after being adjusted for related covariables and baseline TBiL levels (as continuous variable) in the model, the RRs for DR were 1.411 (95% CI: 1.081–1.842) for those who had decreased TBiL level and 0.858 (95% CI: 0.770–0.947) for those who had increased TBiL level during follow-up. And this association was more prominent among those with lower baseline TBiL level.Conclusions. Serum TBiL had a U-shaped relationship with DR incidence, which was independent of control status of diabetes and other related covariates.

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