Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR. OBJECTIVES: To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databases on 1 June 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment, or no treatment for people with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. We excluded studies that used anti-VEGFs in people undergoing vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participants were women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was 8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR, and participants in 11 studies had high-risk PDR (HRPDR). Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The mean number of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding of interventions and outcome assessors. A few studies had selective reporting and attrition bias. No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA compared with PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I2 = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm2, 95% CI -6.84 to -1.43; I2 = 75%; 4 RCTS, 189 eyes; low-certainty evidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I2 = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I2 = 0%; 6 RCTS, 1008 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67, 95% CI 0.49 to 0.93; I2 = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the quality of life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I2 = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not know if anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differences in visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up (< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone. The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates. AUTHORS' CONCLUSIONS: Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.

Vitreous hemorrhage during GLP-1 receptor agonist treatment.

BACKGROUND: The purpose of this case report is to describe a case of vitreous hemorrhage in a patient with a history of diabetic retinopathy and receiving dulaglutide for the management of type 2 diabetes mellitus (T2DM). CASE SUMMARY: A 64-year-old African American male with a past medical history of T2DM and severe diabetic retinopathy for 4 years was restarted on dulaglutide 1.5 mg weekly after being off therapy for 3 months. Baseline laboratory test results included hemoglobin A1c (HbA1c) of 8.8% and random blood glucose (BG) of 280 mg/dL. In addition, the patient had an average fasting BG of 150 mg/dL. In absence of intolerance, the dulaglutide dose was gradually maximized to 4.5 mg weekly and HbA1c decreased to 7.3% and random BG to 121 mg/dL at week 12 since reinitiation. At week 17 of therapy, the patient presented to the emergency department with a 1-day history of vision loss in the left eye and was diagnosed as having vitreous hemorrhage. The etiology for vitreous hemorrhage is unclear and may be a spontaneous episode. In discussion with the patient and the ophthalmologist, dulaglutide was restarted at 1.5 mg once weekly. After 4 weeks of reinitiation, the patient denied any recurrent symptoms of vitreous hemorrhage or worsening diabetic retinopathy. The most recent ophthalmology evaluation indicated no change in diabetic retinopathy. PRACTICE IMPLICATIONS: This case report adds to the limited body of evidence available for the incidence of vitreous hemorrhage in the setting of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) therapy and pre-existing diabetic retinopathy. The case report illustrates that a history of diabetic retinopathy should not automatically preclude the use of GLP-1 RAs.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Small Gauge Vitrectomy with or without Intravitreal Anti-Vascular Endothelial Growth Factor Agents Pretreatment for Proliferative Diabetic Retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a common visual threatening ocular disease, patients with nonclearing vitreous hemorrhage (VH), tractional retinal detachment (RD), or extensive fibrovascular proliferation are always in need for surgical treatment. Although several studies reported better surgical outcome in patients underwent surgery after anti-VEGF injection, the effect of anti-VEGF pretreatment for small gauge vitrectomy in PDR patients remains to be elucidated. OBJECTIVES: The objective of the study was to evaluate the benefits of preoperative anti-VEGF treatment in small gauge vitrectomy for PDR patients. METHODS: A comprehensive literature search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify relevant studies. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal breaks, surgical time, etc.) and postoperative outcome parameters (including best-corrected visual acuity (BCVA), postoperative VH, postoperative RD, etc.). RESULTS: Ten randomized controlled trials were identified and used for comparing small gauge vitrectomy alone (344 eyes, control group) and small gauge vitrectomy with preoperative anti-VEGF injection (355 eyes). The intraoperative findings showed that the surgical time, the incidence of clinically significant intraoperative bleeding, iatrogenic retinal breaks, silicone oil tamponade, and the frequency of endodiathermy were significantly less in the anti-VEGF pre-treated group than in the vitrectomy alone group (p < 0.01). The postoperative findings showed that the incidences of early postoperative VH, postoperative RD were significantly less in the anti-VEGF pre-treated group than in the control group (p < 0.05). The pooled result of postoperative rubeosis iridis/neovascular glaucoma was borderline (p = 0.072) between cases and controls, while no statistically significant differences in BCVA at last follow-up and incidences of late postoperative VH were found between these two groups (p > 0.05). CONCLUSIONS: Anti-VEGF injection prior to small gauge vitrectomy in PDR patients might facilitate easier surgical procedure and reduce intra- and postoperative complications. Further studies are needed to verify our findings and evaluate the optimal interval and dosage for preoperative anti-VEGF injection.

INFUSION-ASSISTED EVACUATION OF SUBMACULAR HEMORRHAGE.

PURPOSE: To report a novel surgical technique for evacuating submacular hemorrhage using the infusion stream of a 25-gauge vitrectomy system. METHODS: Surgical case and video. RESULTS: A 54-year-old man was taken to the operating room for a total hyphema, nonclearing vitreous hemorrhage, and elevated intraocular pressure after multiple tractional retinal detachment repairs by an outside surgeon. Intraoperatively, the hyphema and vitreous hemorrhage were cleared, and the source of bleeding was discovered to be an avulsed vessel through a pre-existing retinal break just superior to the optic nerve. A large submacular hemorrhage was also present that was unable to be drained through the break by aspiration alone. With the vitreous cavity under fluid, the infusion cannula was manipulated to guide the infusion stream onto the macula. The stream was directed in a distal to proximal manner toward the retinal break, and the submacular blood was successfully expressed out through the break. Postoperatively, the retina remained attached with almost complete resolution of the submacular hemorrhage. CONCLUSION: Using the mechanical pressure of the infusion stream can be an effective method for evacuating large subretinal hemorrhages.

A Caveat About Financial Incentives for Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Retinopathy.

PURPOSE: To highlight the financial incentive to the physician of choosing an intravitreal anti-vascular endothelial growth factor (VEGF)-based strategy for treating non-proliferative and proliferative diabetic retinopathy, and its possible risks to the patient and costs to the health care system. DESIGN: Perspective with retrospective cost and profit analysis. METHODS: Review and synthesis of selected literature on the treatment of diabetic retinopathy, with interpretation of activity-based and time-based costing of an intravitreal aflibercept strategy for diabetic retinopathy. Data from the DRCR Retina Network Protocols W and AB and PANORAMA trial were used to illustrate the potential financial incentive underlying such a treatment strategy. RESULTS: Physician treatment algorithms for diabetic vitreous hemorrhage and non-proliferative diabetic retinopathy may be influenced by the substantial financial incentives that intravitreal aflibercept strategies present, despite functional equivalence with alternative and less profitable strategies. For example, pursuing an intravitreal aflibercept-based strategy for diabetic vitreous hemorrhage presents a 76% increased profit over pars plana vitrectomy with laser, with equivalent functional outcomes. For non-proliferative diabetic retinopathy, preventative aflibercept injections represent a potential 414% increase in profit over observation and an increased cost of $12,164 to $17,542 over 2 years per patient, with no improvement in visual function. These findings demonstrate that there may be misaligned financial incentives in the management of diabetic retinopathy. CONCLUSIONS: While anti-VEGF therapy is a useful tool in the management of proliferative diabetic retinopathy and diabetic macular edema, it is believed that physicians should avoid overreliance on anti-VEGF injections in the treatment of diabetic retinopathy. Retinal specialists should be cognizant of the limitations, costs, and risks of anti-VEGF monotherapy and prophylactic therapy, and of the imperative to avoid bias towards financially remunerative practice patterns when equally effective alternatives exist.

Myelin oligodendrocyte glycoprotein antibody-associated bilateral optic neuritis with unilateral prepapillary vitreous hemorrhage.

We present a case of bilateral myelin oligodendrocyte glycoprotein antibody optic neuritis (MOG-ON) with unilateral vitreous hemorrhage in a 6-year-old boy. Multidisciplinary team care, including extensive investigations and prolonged follow-up, excluded alternative causes of vitreous hemorrhage. Early suspicion and diagnosis of MOG-ON led to timely intravenous methylprednisolone treatment, with protracted oral steroid taper, resulting in complete resolution of optic nerve swelling, vitreous hemorrhage, and visual function.

The efficacy and safety of intravitreal injection of Ranibizumab as pre-treatment for vitrectomy in proliferative diabetic retinopathy with vitreous hemorrhage.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become first line therapy for diabetic macular edema. This study evaluated the efficacy and safety of intravitreal injection of Ranibizumab (IVR) as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy (PDR) patients with vitreous hemorrhage. METHODS: This pilot randomized controlled trial included 48 eyes with vitreous hemorrhage resulting from active PDR. Eyes were treated with IVR 1 or 3 days before vitrectomy or a sham subconjunctival injection 3 days before surgery. The occurrence of new tractional retinal detachment (TRD), total operation time, and intraoperative findings were compared. The concentrations of VEGF and connective tissue growth factor (CTGF) in aqueous humor and plasma collected at the time of IVR and vitrectomy were determined by ELISA. RESULTS: None of the patients who received IVR experienced new TRD. Ranibizumab injection improved intraoperative outcomes. The mean concentrations of VEGF in aqueous humor were significantly lower after than before IVR in patients who received IVR 1 and 3 days before surgery (P < 0.001 each). The CTGF/log10 (VEGF) ratio was significantly higher after than before IVR in patients who received IVR 3 days before vitrectomy (P = 0.046). CONCLUSION: Preoperative IVR is an effective and safe strategy for the surgical treatment of severe PDR combined with vitreous hemorrhage. IVR 1 and 3 days before surgery can significantly reduce VEGF content in aqueous humor and effectively improve intraoperative conditions without causing TRD. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry. Name of the registry: Exploratory analysis of effect of intravitreal ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. TRIAL REGISTRATION NUMBER: ChiCTR-ONC-16009520. Date of registration: October 20, 2016. URL of trial registry record: http://www.chictr.org.cn/searchprojen.aspx.

Iodine-125 Plaque Radiotherapy for Retinoblastoma Recurrence Following Intra-arterial Chemotherapy.

PURPOSE: To assess the efficacy and toxicity of Iodine-125 (I-125) plaque radiotherapy for retinoblastoma following intra-arterial chemotherapy (IAC). METHODS: Clinical records of patients with retinoblastoma who received I-125 plaque radiotherapy after IAC at the Ocular Oncology Service at Wills Eye Hospital between December 1, 2009 and April 30, 2020, were retrospectively reviewed. RESULTS: Forty-one retinoblastomas in 41 eyes of 41 patients were treated with I-125 plaque radiotherapy after IAC at a median age of 32 months. The indication for plaque radiotherapy was solid tumor recurrence with or without overlying subretinal/vitreous seeds (n = 33, 80%), subretinal seeds alone (n = 6, 15%), and vitreous seeds alone (n = 2, 5%). The median irradiated basal diameter and thickness was 9 and 4 mm, respectively. Mean radiation dose to tumor apex was 3,483 centigray (cGy) delivered at mean rate of 35 cGy/hr. The irradiated site was controlled in 39 eyes (95%) at a median of 20 months after plaque radiotherapy for solid tumor (31 of 33, 94%), subretinal (6 of 6,100%), and vitreous seeds (2 of 2, 100%). A subgroup of tumors occurring within an ischemic retinal/choroidal field was identified on fluorescein angiography (n = 24) and demonstrated control in 22 of 24 (92%). Using Kaplan-Meier analysis, radiation complications at 2 years included vitreous hemorrhage (37%), retinopathy (28%), papillopathy (18%), and cataract (18%). Five eyes (12%) were enucleated for recurrence outside the irradiated area, chronic vitreous hemorrhage, and/or total retinal detachment. CONCLUSIONS: Iodine-125 plaque radiotherapy provided 95% control for retinoblastoma tumors that failed IAC, including those in ischemic fields untreatable with further chemotherapy. Radiation complications should be anticipated in eyes exposed to substantial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2022;59(3):164-171.].

Vitreous hemorrhage: A rare ophthalmic adverse effect due to imatinib treatment.

INTRODUCTION: Imatinib is generally well tolerated by patients. The most common ophthalmic side effects are eyelid edema and periorbital edema. Other side effects which occur at rates of <1% include blepharitis, blurred vision, conjunctival hemorrhage, conjunctivitis, retinal hemorrhage, etc. An uncommon case is here reported of a 51-year-old male with chronic myeloid leukemia who developed vitreous hemorrhage due to imatinib after 9 months of treatment. CASE REPORT: A 51-year-old male with leukocytosis detected in the blood test examination was referred to the Hematology Department. The bone marrow biopsy result was compatible with chronic myeloid leukemia. Imatinib treatment (400 mg/day) was started. In the ninth month of imatinib treatment, the patient complained of a sudden decrease in vision. Vitreous hemorrhage was detected in the left eye and the patient underwent surgery. Vitreous hemorrhage recurred 1 month after the operation. On the fourth day after the discontinuation of imatinib treatment, the patient's ophthalmic complaints improved significantly. The Naranjo algorithm was applied and a score of 9 was detected. The vitreous hemorrhage of the patient was attributed to imatinib, and so the treatment of the patient was switched to bosutinib. DISCUSSION: Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). The conjunctiva and sclera have a large amount of c-kit positive mast cells which are inhibited by imatinib. The inhibition of c-kit positive mast cells by imatinib may be responsible for further exposure of the conjunctival mucosa to injuries.

Visual Outcomes in Eyes With Neovascular Glaucoma and Anterior Segment Neovascularization Without Glaucoma.

PURPOSE: To find predictive factors of neovascular glaucoma (NVG) development in eyes with anterior segment neovascularization without glaucoma (ASNVWG), and poor visual outcomes in eyes that have already developed NVG. DESIGN: Retrospective, clinical cohort studies. METHODS: A retrospective chart review was performed on 106 eyes of 94 patients with ASNVWG and 245 eyes of 225 patients with NVG. Measured outcomes included the development of NVG at any time point of the disease for the ASNVWG arm, and a visual acuity of ≤20/200 at 6 months after initial presentation for the NVG arm. RESULTS: Overall, 25% of ASNVWG eyes progressed to NVG. Progression was associated with retinal vein occlusion (RVO) (P < .01), lower median presenting BCVA (P < .01), and concurrent traction retinal detachments (TRDs) (P = .025). Sixty-eight percent of NVG eyes had a BCVA of ≤20/200 by 6-month follow-up, which was associated with RVO (P = .005), vitreous hemorrhage on presentation (P = .001), and no panretinal photocoagulation (PRP) treatments (P < .001). BCVA >20/200 at 6 months was associated with ≥1 PRP or intravitreal bevacizumab (IVB) treatment within 1 week of presentation or ≥3 PRP or IVB treatments overall (P < .001). CONCLUSION: RVO, presenting visual acuity, and concurrent TRD are risk factors for NVG in eyes with ASNVWG. In eyes with NVG, RVO and concurrent vitreous hemorrhage are risk factors for ≤20/200 vision at 6 months, whereas treatment with ≥1 PRP or IVB within 1 week of presentation, or ≥3 treatments of PRP or IVB within 6 months are protective.

Outcomes of preoperative bevacizumab in diabetics with nonclearing vitreous hemorrhage without tractional detachment - A quasi-randomized retrospective study.

PURPOSE: To assess whether preoperative bevacizumab (BVZ) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH) without tractional retinal detachment (TRD) leads to lesser macular edema and better visual outcome compared to eyes that do not receive BVZ. METHODS: This quasi-randomized retrospective study included 217 treatment-naïve eyes with nonclearing VH without TRD that had vitrectomy with or without BVZ and had a minimum 6-months follow-up. Postoperative variables, including visual acuity (BCVA), central macular thickness (CMT) at 1 month, and need for additional anti-VEGF injections till 6 months follow-up, were recorded for analysis. RESULTS: Of the 217 eyes, 107 eyes (49%) received preoperative BVZ and 110 (51%) did not. Groups were comparable in terms of preoperative characteristics. At 1 month, mean CMT was significantly higher in eyes without BVZ (310 ± 33 m vs. 246 ± 34m; P < 0.001). The likelihood of developing center-involving DME at 1 month after vitrectomy was 67% lower if the eye received preoperative BVZ (OR = 0.33, 95%CI = 0.18-2.54, P = 0.56). Though BCVA improved significantly in both groups at 1 month, it was 1/3rd of a line better in the BVZ group (b coefficient = -0.035 logMAR, 95%CI = -0.04 to -0.008 logMAR, P = 0.01). CONCLUSION: Preoperative BVZ in treatment-naïve eyes with PDR and VH but without TRD lead to better macular status and marginally improved vision at 1 month, which was maintained at 6 months. In view of these results, patients may be offered BVZ only when it is readily affordable to them.

Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. OBJECTIVE: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. INTERVENTIONS: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. MAIN OUTCOMES AND MEASURES: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. RESULTS: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was -4.3 (95% CI, -10.6 to 1.9) compared with -16.7 (95% CI, -24.4 to -9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P < .001). CONCLUSIONS AND RELEVANCE: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02858076.

Efficacy of bevacizumab for vitreous haemorrhage in proliferative diabetic retinopathy with prior complete panretinal photocoagulation.

PURPOSE: To investigate the efficacy of intravitreal bevacizumab injections (IVBs) for vitreous haemorrhage (VH) in proliferative diabetic retinopathy (PDR) with prior complete panretinal photocoagulation (PRP). METHODS: A multicentre cohort study of eyes with new VH in PDR after documented previous complete PRP was performed. Eyes were grouped according to IVB treatment at baseline, and cumulative rate of vitrectomy and spontaneous clear-up rate were compared as the main outcome. Eyes requiring vitrectomy within 1 month, or with tractional retinal detachment (TRD), or with spontaneous clear-up within 1 month, were excluded. RESULTS: In total, 44 eyes with IVB and 92 control eyes without IVB were followed up to 20.1 months. Cumulative probability of vitrectomy was lower in the IVB group at 12 months (0.16 vs 0.42, IVB vs controls), and throughout the follow-up period (p = 0.005). Cumulative probability of spontaneous clear-up was higher in the IVB group at 12 months (0.81 vs 0.68, IVB vs controls), and throughout the follow-up period (p = 0.013). Best-corrected visual acuity (BCVA) at 1 month after onset of VH was significantly better in the IVB group (0.513 vs 0.942 logarithm of the minimal angle of resolution, p = 0.002); however, the difference of BCVA lost significance with further follow-up. IVB treatment was the only factor significantly associated with vitrectomy risk on multivariate analysis (p = 0.047, hazard ratio 0.506). CONCLUSION: In VH after prior complete PRP, IVB was effective in decreasing vitrectomy requirement, although overall visual benefit was short-term. IVB can be considered to defer vitrectomy in PDR VH eyes with prior complete PRP and no TRD.

RESPONSE TO INTRAVITREAL AFLIBERCEPT IN A PATIENT WITH PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY.

PURPOSE: To draw attention to a novel treatment agent for vision loss associated with peripheral exudative hemorrhagic chorioretinopathy. METHODS: The case of an 83-year-old man suffering with loss of left visual acuity vision in the context of vitreous hemorrhage secondary to peripheral exudative hemorrhagic chorioretinopathy is described. RESULTS: Resolution of vitreous hemorrhage and subretinal hemorrhage was demonstrated after treatment with aflibercept. CONCLUSION: Peripheral exudative hemorrhagic chorioretinopathy is discussed in terms of its presentation, pathophysiology, and existing treatment methodologies.

Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. Design, Setting, and Participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. Main Outcomes and Measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept. Conclusions and Relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.

Efficacy and safety of Chinese medicines for vitreous hemorrhage: A protocol for systematic review and meta-analysis.

BACKGROUND: Vitreous hemorrhage (VH) is a common ophthalmic disease with a high rate of blindness, which will seriously affect the quality of life of patients and bring great burden to patients' families and society. The treatment for VH contains medical therapy, lasers, and surgery. At present, there is no recognized western medicine with definite curative effect and little side effect for the treatment of VH. In most cases, PRP is not available to treat VH; intravitreal injection or surgical treatment is adopted as the primary therapy. However, in the long-term treatment, the effect of the above-mentioned treatment is not satisfactory, so many patients choose oral Chinese medicines, which has been widely used in China to treat VH. Numerous clinical trials have demonstrated that Chinese medicines can promote the absorption of VH and improve the visual function of patients. The purpose of this review is to evaluate the efficacy and safety of Chinese medicines in the treatment of VH and inform a decision aid for the clinical encounter between patients and clinicians. Besides, it is beneficial to establish a future research agenda. METHODS: The systematic review will include all of the randomized controlled trials on the efficacy and safety of Chinese medicines for VH. Nine electronic databases, namely PubMed, Web of Science, EMBASE, the Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal database (VIP), and CBM, will be searched normatively on the basis of the rule of each database from the inception to August 31, 2019. We will also search registers of clinical trials, potential gray literature, and conference abstracts. There are no limits on language and publication status. The literature screening, data extraction, and quality assessment will be conducted by 2 reviewers independently. The reporting quality and risk of bias will be assessed by other 2 researchers. Standard of curative effect and total treatment efficacy rate were assessed as the primary outcome. The secondary outcomes will include the curative effect of single symptom and sign, the improvement rate of single auxiliary examination, withdrawal and reduction of western medicines in a course of treatment, maintenance of western medicines after the course of treatment, laboratory efficacy indexes. Meta-analysis will be performed using RevMan5.3 software provided by the Cochrane Collaboration. RESULTS: This study will provide a comprehensive review based on current evidence of Chinese medicines treatment for VH in several aspects, including standard of curative effect, total treatment efficacy rate, the curative effect of single symptom and sign, the improvement rate of single auxiliary examination, withdrawal and reduction of western medicines in a course of treatment, laboratory efficacy indexes, total treatment efficacy, and safety, among others. CONCLUSION: The conclusion of this study will provide evidence to determine whether Chinese medicines are an effective and safe intervention for patients with VH. ETHICS AND DISSEMINATION: It is not necessary to obtain ethical approval for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020152321.

Intravitreal Aflibercept injection with Panretinal photocoagulation versus early Vitrectomy for diabetic vitreous hemorrhage: randomized clinical trial.

BACKGROUND: To compare efficacy and safety of intravitreal aflibercept (IVA) injection with panretinal photocoagulation (PRP) versus early vitrectomy for diabetic vitreous hemorrhage (VH). METHODS: Prospective, randomized study that included 34 eyes with diabetic VH. They were divided into two groups, Group Ι (17 eyes) received three successive IVA injections followed by PRP and group ΙΙ (17 eyes) for whom early vitrectomy was done. Follow up was carried out after one, two, three, six and nine months. The primary outcome measure was change in the mean best corrected visual acuity (BCVA) after nine months, secondary outcome measures were mean duration of clearance of VH and rate of recurrent hemorrhage with any additional treatment in both groups. Complications were reported. RESULTS: There was no statistically significant difference regarding initial demographic criteria between both groups. The mean final log MAR BCVA was statistically better than the initial BCVA in both groups (0.51 ± 0.20, 1.17 ± 0.48 for group I and 0.48 ± 0.18, 1.44 ± 0.44 for group II, P < 0.001). There was no statistically significant difference between both groups regarding the mean final Log Mar BCVA (0.51 ± 0.20 for group I, 0.48 ± 0.18 for group II, p ≥ 0.05), the mean duration of clearance of VH was 7.8 ± 1.8 weeks, 5 days for group I and II respectively. PRP was completely done for all eyes in group I after three months. The difference in the recurrence rate between group I (29.4%) and group II (11.8%) was statistically significant (p < 0.05). Vitrectomy was done for three eyes (17.6%) due to recurrent non-resolving VH in group I. late recurrent VH occurred in two eyes (11.8%) in group II, IVA was given with complete clearance of the hemorrhage. No vision threatening complications were reported in both groups. CONCLUSION: Both intravitreal injection of aflibercept followed by PRP and early vitrectomy are effective and safe modalities for treatment of diabetic vitreous hemorrhage. Early vitrectomy leads to faster vision gain with less incidence of recurrence than intravitreal injection. TRIAL REGISTRATION: Randomized clinical trial under the number of NCT04153253 on November 6, 2019 "Retrospectively registered".