Intravitreal antivascular endothelial growth factor in diabetic macular oedema: scoping review of clinical practice guidelines recommendations

BackgroundDiabetic macular oedema (DME) is a worldwide major cause of low vision and blindness. Intravitreal antivascular endothelial growth factor (anti-VEGF) constitutes an effective treatment. Clinical practice guidelines (CPGs) are synthesis documents that seek to improve patient care.ObjectivesTo identify CPGs that make anti-VEGF recommendations for DME and to assess their reporting quality and their considerations when making recommendations.Eligibility criteriaCPGs published between December 2009 and December 2019 that make explicit anti-VEGF recommendations in DME.Sources of evidenceSensitive search strategy in Embase, Google Scholar and hand-searching on 165 websites.MethodsWe extracted information from each CPG with a previously piloted sheet. Two independent authors applied theAppraisal of Guidelines, Research and Evaluation tool (AGREE-II) assessment for each CPG.ResultsThe 21 included CPGs recommend anti-VEGF for DME, but there is a wide variation among the clinical aspects included, such as location of DME, visual acuity required, therapeutical alternatives or discontinuation. Most have a poor quality of reporting based on the AGREE-II tool assessment, especially those developed by ophthalmological societies, those that have an exclusive content about DME, and those where most of their authors disclose conflict of interest (COI) with pharmaceutical industry or where their authors did not report COIs. Pharmaceutical-sponsored CPGs did not use systematic reviews (SRs) to support their recommendations. Very few recommendations consider patient values and preferences, equity, acceptability and feasibility of the intervention.ConclusionsMost of the CPGs that made recommendations of anti-VEGF for DME have poor quality of reporting, do not use SRs and do not consider patients’ values and preferences.

Choroidal Vascularity Index as a Biomarker for Visual Response to Antivascular Endothelial Growth Factor Treatment in Diabetic Macular Edema

Purpose. To investigate the choroidal vascularity index (CVI) as a prognostic factor for the visual efficacy of antivascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME). Methods. We retrospectively reviewed 92 DME eyes receiving anti-VEGF treatment, which were stratified as responders (≥5 letters gained) and nonresponders (<5 letters gained or lost). Baseline systematic features and optical coherence tomography features, including the CVI, adjusted ellipsoid zone (EZ) reflectivity, subretinal fluid (SRF), and disorganization of the retinal inner layers (DRIL), were evaluated between the two groups. Results. The baseline CVI was significantly lower in nonresponders than in responders ( 0.66 ± 0.05 , 0.69 ± 0.05 , and 0.72 ± 0.05 , p = 0.014 ). After adjusting for other factors, the baseline CVI, DRIL, SRF, and adjusted EZ reflectivity were significantly associated with visual outcomes (CVI: odds ratio OR = 0.17 , p = 0.006 ; adjusted EZ reflectivity: OR = 0.56 , p = 0.007 ; DRIL: OR = 6.71 , p = 0.001 ; and SRF: OR = 0.29 , p = 0.008 ). Conclusion. DME patients with a higher CVI, higher adjusted EZ reflectivity, the presence of SRF, and the absence of DRIL at baseline were more likely to gain >5 letters in visual acuity after anti-VEGF treatment. CVI may serve as a novel biomarker for visual response to anti-VEGF treatment in DME.

Role of Anti-VEGF (Bevacizumab) in Management of Neovascular Glaucoma: A Review

Neovascular glaucoma (NVG) is an aggressive type of glaucoma, which often results in poor visual outcomes. Antivascular endothelial growth factor is frequently used for various conditions in which VEGF release is induced in response to retinal ischemia. Bevacizumab is a humanized anti-VEGF monoclonal IgG1 antibody. The potential of antivascular endothelial growth factor (anti-VEGF) agents to modify the disease course of neovascular glaucoma (NVG) was recognized shortly after their use in the treatment of age-related macular degeneration was reported. These medications were noted to induce rapid regression of the anterior segment neovascularization that characterizes NVG. Several studies as well as extensive clinical experience have demonstrated a rapid regression of anterior segment neovascularization following the injection of anti-VEGF agents. This review aims to summarize current evidences regarding effectiveness of Bevacizumab in management of neovascular glaucoma.

Outcomes of eyes with retinal vein occlusion that are lost to follow-up after antivascular endothelial growth factor therapy

Background/aimsTo evaluate the outcomes of eyes with macular oedema due to retinal vein occlusion (RVO) that are lost to follow-up (LTFU) after antivascular endothelial growth factor (VEGF) injections.MethodA retrospective, single-centre, consecutive case series of RVO patients receiving injections who were LTFU >6 months was conducted. Data were collected from the visit before LTFU; return visit; 3 months, 6 months and 12 months after return; and the final visit.ResultsNinety eyes of 83 patients were included. Fifty (55.5%) eyes had branch RVO and 40 (44.5%) had central RVO. Mean LTFU duration was 277.8 days with additional mean follow-up for 748.1 days after return. Mean logarithm of the minimum angle of resolution visual acuity (VA) (Snellen) at the visit before LTFU was 0.72 (20/105) which worsened on return [1.04 (20/219), p<0.001) and remained worse at all timepoints after return: 0.92 (20/166) at 3 months (p<0.001), 0.97 (20/187) at 6 months (p<0.001), 0.94 (20/174) at 12 months (p<0.001) and 1.01 (20/205) at final visit (p<0.001). Mean central foveal thickness (CFT) increased from 252 µm at the visit before LTFU to 396 µm at the return visit (p<0.001). No difference in CFT was noted by 3 months (258 µm, p=0.71), 6 months (241 µm, p=0.54) or 12 months after return (250 µm, p=0.95). CFT was thinner at the final visit (215 µm, p=0.018).ConclusionRVO patients receiving anti-VEGF injections who were LTFU experienced a decline in VA that did not return to the levels seen before LTFU despite improvement in CFT after restarting therapy, underscoring the importance of ongoing treatment.

Association between Inflammatory Factors in the Aqueous Humor and Hyperreflective Foci in Patients with Intractable Macular Edema Treated with Antivascular Endothelial Growth Factor

Background. To evaluate the correlations between the inflammatory factors in the aqueous humor and hyperreflective foci (HRF) in patients with intractable macular edema treated with antivascular endothelial growth factor (anti-VEGF). Methods. This study included 17 patients with intractable macular edema (ME) treated with anti-VEGF agents. Inflammatory factors in the aqueous humor were measured by the Cytometric Beads Array before injection, and the numbers of HRF pre- and post-anti-VEGF treatment were counted from four different directions (90 degrees, 45 degrees, 180 degrees, and 135 degrees) in the SD-OCT images, respectively, before treatment and one month after treatment. The correlations between inflammatory factors and the numbers of HRF were assessed. Results. The numbers of HRF were reduced significantly after anti-VEGF treatment. The change in the HRFs at the 90-degree location was significantly positively correlated with IL-8 and VCAM-1. The change of all HRFs was significantly positively correlated with IL-8. The HRFs before the treatment also had a positive correlation with IL-8 and VCAM-1. Conclusion. After anti-VEGF treatment, the numbers of HRF in intractable ME declined greatly. The higher the levels of IL-8 and VCAM-1 before treatment, the more significant the reduction of HRF after anti-VEGF treatment, which indicated that HRF could be an effective noninvasive imaging indicator for evaluating the effect of anti-VEGF on intractable macular edema. The OCT images at the 90-degree location could better show the inflammatory reaction of patients and also had better clinical significance for the prognosis evaluation of ME associated with inflammation.

Changes in Macular Microvascular Structure in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Antivascular Endothelial Growth Factor for One Year

Purpose. To observe the changes in macular microvascular structure and the correlation between anatomy and visual function in patients with macular edema secondary to branch retinal vein occlusion (BRVO) treated with antivascular endothelial growth factor for one year. Methods. This prospective study enrolled 39 patients (one eye per patient) who received intravitreal injections of ranibizumab for macular edema secondary to BRVO. All patients received a minimum of 3 initial monthly ranibizumab injections and criteria-driven pro re nata (PRN) dosing thereafter for visual acuity (VA) and central retinal thickness (CRT) stabilization. The follow-up period of this study was one year. The vascular density (VD) of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter, the VD within a 300 μm wide ring surrounding the FAZ (FD-300), and the acircularity index (AI) were measured automatically by optical coherence tomography angiography (OCTA) at baseline, month 6, and month 12. Results. Compared with those before treatment, the VD of the SCP significantly decreased 6 months after treatment ( P < 0.05 ), while the area and perimeter of the FAZ increased significantly ( P < 0.01 ). After 12 months of treatment, the area and perimeter of the FAZ increased significantly ( P < 0.01 ). There was no significant difference in any parameters between 12 months and 6 months after treatment ( P > 0.05 ). The change in BCVA was negatively correlated with the VD of the SCP at 12 months ( P = 0.0447 , r = −0.3233). There was a relationship between the DBP and AI, and CRT was related to VD of DCP at baseline ( P = 0.028 , 0.0209 ; r = 0.383, −0.384). The PERIM and AI at 12 months were significantly associated with the recurrence of macular edema, and the changes in vascular density in the SCP and PERIM were significantly associated with the number of injections within 12 months ( P < 0.05 ). Conclusions. One year after ranibizumab treatment, the area and perimeter of the FAZ were enlarged, while the VD of the SCP and DCP remained stable, which indicated that ranibizumab treatment did not improve macular blood supply and macular ischemia in BRVO patients.