Comparison of the Efficacy and Safety of Conbercept Plus Panretinal Photocoagulation Versus Panretinal Photocoagulation Alone for Proliferative Diabetic Retinopathy: A Multicenter, Prospective, Randomized Controlled Study

To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage (VH). No major adverse events were identified. The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.

To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

Panretinal photocoagulation (PRP) is the current standard of care in proliferative diabetic retinopathy (PDR). However, treatment with anti-vascular endothelial growth factor agents might offer better patient outcomes with fewer side-effects. The PRIDE study aimed to assess the efficacy and safety of ranibizumab with or without PRP compared with PRP alone in patients with PDR. A total of 106 PDR patients without diabetic macular oedema were randomized to receive ranibizumab 0.5mg monotherapy (n=35), PRP (n=35) or combined ranibizumab 0.5mg/PRP (n=36). The primary objective of this 12-month, multicentre, phase II study was to investigate the change in area of retinal neovascularization (NV). Complete regression of leakage and best-corrected visual acuity (BCVA) were key secondary end-points. At Month 12, there was a statistically significant difference of -2.83mm² in the least square mean change in NV area between the ranibizumab monotherapy and PRP group, favouring ranibizumab (95% CI [-5.45; -0.21], p=0.0344). At Month 3, 67%/0%/67% of the patients in the ranibizumab/PRP/combination groups, respectively, showed complete regression of leakage from NVs, while at Month 12, 28%/8%/18% showed complete regression of leakage from NVs. BCVA change was greater in the ranibizumab group compared with the PRP monotherapy group at Month 12 (+1.6 letters; 95% CI [-2.3; 5.5] versus -3.9 letters; 95% CI [-7.8; -0.1], p=0.0495). Ranibizumab monotherapy is an alternative treatment option to laser treatment in patients with PDR. Ranibizumab showed stronger effects on NV leakage and area reduction while offering better visual acuity results than PRP alone.

Ranibizumab for Retinal Neovascularization

To report short-term regression of neovascularization after varying intravitreal doses of bevacizumab (Avastin®; Genentech, San Francisco, California, USA) in patients with proliferative diabetic retinopathy (PDR). Eighty eyes from 76 patients with active neovascularization of the disc (NVD) or elsewhere (NVE) caused by PDR were divided into four groups and treated with a single intravitreal bevacizumab (IVB) injection of 1.25 mg, 600 μg, 300 μg or 150 μg, respectively. All patients underwent ophthalmoscopic examination and fluorescein angiography at baseline, 1 week, 1 month and 2 months later. No significant ocular or systemic adverse events were observed. In all patients with NVD or NVE, complete resolution of leakage was recorded within the first week or the first month of the injection. Even with the lowest dose (150 μg), regression of neovascularization appeared as early as the first week and lasted for over a month. Recurrence of fluorescein leakage was observed in all groups after the first month and did not correlate with the extent of neovascularization or IVB dose. Short-term results suggest that IVB given below the standard dosage (150–300 μg compared to 1.25 mg) can lead to the achievement of complete regression of diabetic retinal neovascularization within 30–45 days of injection.

Purpose: This article evaluates the influence of baseline diabetic macular edema (DME) on cost-utility analysis of treatment for proliferative diabetic retinopathy (PDR) based on 5-year Diabetic Retinopathy Clinical Research Network ( DRCR.net ) Protocol S results. Methods: A decision-analysis model calculated comparative cost utility of panretinal photocoagulation (PRP) and intravitreal ranibizumab (IVR) treatment for PDR with and without baseline DME. Centers for Medicare &amp; Medicaid Services data were used to calculate associated modeled costs in a hospital/facility-based and nonfacility setting. Cost utility was calculated based on the preserved visual utility and estimated life years remaining. Sensitivity analyses were performed to evaluate the impact of the model’s assumptions. Results: The modeled cost per quality-adjusted life year (QALY) of treatment for PDR with baseline DME for 5 years of utility in the facility (nonfacility) setting was $280,919 ($203,444) in the PRP group and $452,387 ($339,319) in the IVR group. The estimated lifetime cost per QALY in the facility (nonfacility) setting was calculated as $84,761 ($50,077) in the PRP group and $314,483 ($230,301) in the IVR group. The cost per QALY of IVR for the first 5 years of treatment was 1.6 to 1.7 times that of PRP, whereas lifetime cost per QALY was 3.7 to 4.6 times higher. When considering all patients regardless of baseline DME status, lifetime cost per QALY of PRP was 8% to 13% higher, whereas IVR was only 1% higher compared with the cost per QALY without baseline DME. Conclusions: When considering the subset of patients with PDR and baseline DME, PRP maintains a more favorable cost utility compared with IVR. This augments previous reports that PRP has a more favorable cost utility than IVR for PDR without DME, given the marginal visual benefit of IVR.

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. To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use. 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. 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. 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. 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. 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.

Objectives: To evaluate maintenance of existing vision after pan retinal photocoagulation in type II diabetes with proliferative diabetic retinopathy and to assess the causes of severe visual loss after pan retinal photocoagulation (PRP). Materials and Methods: 50 eyes of 28 patients with proliferative diabetic retinopathy (PDR) attending the retina clinic were included in this study. After detailed ocular examination and fundus fluorescein angiography, patients were treated with PRP. After PRP, visual acuity testing and retinal examination was done after 1 month, 3 months, 6 months and 1 year. Results: At baseline 30% eyes had visual acuity of 6/6- 6/9, 44% had visual acuity of 6/12-6/36 and 26% eyes had visual acuity of <6/60. 73.3% of patients with visual acuity 6/6- 6/9 at baseline retained their vision, 26.67% had decreased vision. 86.36% of patients with visual acuity 6/12- 6/36 at baseline retained their vision, 9.09% had decreased vision and 4.55% of patients had improved vision. 92.30% with poor baseline visual acuity (≤6/60) retained the same visual acuity and 7.69% of them improved to 6/9 at the end of 1 year. Causes of visual loss following PRP at the end of 1 year included vitreous hemorrhage (33.33%), pre retinal hemorrhage (33.33%), epiretinal membrane (33.33%), tractional retinal detachment (8.33%), macular edema (8%), choroidal effusion (8%), and acceleration of pre retinal fibrosis (8%). Conclusion: After PRP, visual acuity was maintained at baseline in majority of patients. However, decreased vision seen in few patients occured due to vitreous hemorrhage, pre retinal hemorrhage and macular edema. Key words: Panretinal photocoagulation (PRP), Proliferative Diabetic Retinopathy (PDR), Early treatment diabetic retinopathy study (ETDRS), Fundus fluorescein angiography (FFA).

Clinical Characteristics and Surgical Outcomes of Patients Undergoing Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy

To assess efficacy of intravitreal conbercept (IVC) injection in combination with panretinal photocoagulation (PRP) vs PRP alone in patients with severe nonproliferative diabetic retinopathy (SNPDR) without macular edema (ME). Forty-eight patients with SNPDR without ME (56 eyes) were divided into the PRP group and IVC+PRP group (the pulse group) in this retrospective clinical study. Conbercept was intravitreally administered to patients in the pulse group 1wk before treatment with PRP and followed up for 1, 3, and 6mo. The best-corrected visual acuity (BCVA, logMAR), center foveal thickness (CFT), visual acuity (VA) improvement, and adverse reactions were compared between groups. In the PRP group, the BCVA reduced at 1 and 3mo before improving at 6mo. In the pulse group, baseline BCVA decreased continuously at 1mo, increased at 3 and 6mo. BCVA in the pulse group was better than that in the PRP group at 1, 3, and 6mo. There was an increase in CFT in the PRP group during follow-up compared with baseline. In the pulse group, CFT was increased at 1mo relative to baseline, steadily decreased to the baseline level at 3 and 6mo. There was a more significant reduction in CFT in the pulse group during follow-up compared with the PRP group. The effective rates of VA in the PRP and the pulse groups were 81.48% and 100%, respectively. As PRP pretreatment, a single dose of IVC administration has beneficial effects for preventing PRP-induced foveal thickening and increasing VA in patients with SNPDR without ME.

The Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities. To evaluate incremental cost-effectiveness ratios of 0.5-mg ranibizumab therapy vs PRP for PDR. Preplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015. Intravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive ranibizumab for concomitant DME. Incremental cost-effectiveness ratios of ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME. The study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and 25 to the PRP group (plus ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years. Over 2 years, compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME. Clinicaltrials.gov Identifier: NCT01489189.

Purpose:The current study aimed to evaluate changes in peripapillary retinal nerve fiber layer (RNFL) thickness in diabetic patients with bilateral proliferative diabetic retinopathy (PDR) after receiving panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB) with PRP.Methods:Ocular examination and peripapillary optical coherent tomography (OCT) were performed for each patient at baseline, 1, 3, 6, and 10 months after treatment. Both eyes of each patient were randomized into either PRP or PRP + IVB group.Results:Sixty-four eyes (32 patients) were enrolled in this randomized clinical trial. In the PRP group, global RNFL thickness initially increased and reached statistical significance in the third month (from 105.9 ± 21.4μm at baseline to 119 ± 41.6μm at 3 months, P = 0.03). Subsequent decline was observed with no significant difference from baseline at 10 months (106 ± 19.3μm, P = 0.914). There were no statistically significant changes in the PRP + IVB group (from 101.7 ± 22.2μm at baseline to 109.3 ± 26.9μm at 3 months, P = 0.996 and 101.9 ± 16.5μm at 10 months, P = 0.999). In the latter group, slight increase in RNFL thickness was observed in the first month (107.7 ± 21.1μm). RNFL thickness was similar to baseline in the two groups at month 10, with the exception of significant increase in superior-temporal sector in the PRP group (145.3 ± 13.4μm vs. 127.2 ± 17.3μm, P = 0.045).Conclusion:Compared to eyes treated with PRP, eyes treated with adjunctive IVB showed less significant post-treatment changes in RNFL thickness.

Anterior chamber depth and intraocular pressure following panretinal argon laser photocoagulation for diabetic retinopathy

Background: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes with the potential to cause severe vision loss and blindness and a devastating effect on quality of life.Objective: Discuss the macular ganglion cell and retinal nerve fiber layer (RNFL) changes after laser treatment as a management of diabetic retinopathy.Patients and Methods: This study was carried out on 55 eyes of 35 patients designed as a prospective, interventional case series at Sohag Ophthalmic Diagnostic Laser Unit between January 2016 and March 2017.A complete ophthalmologic examination was performed, including best-corrected visual acuity (BCVA) using the ETDRS charts, intraocular pressure (IOP) measurement, slit-lamp biomicroscopic examination, fundus examination, fluorescein angiography, and 3D optical coherence tomography (OCT) 2000. Results:The value of RNFL (superior and total) in the GRID group is more than in the pan-retinal photocoagulation (PRP) group which increased at 1 month post laser (not significant) then significantly decreased at 6 month follow up.The value of RNFL (inferior) in the GRID group is more than in the PRP group which significantly increased at 1 month post laser then decreased at 6 month follow up table 4. Conclusion: Significant ganglion cell (GC) and RNLF decrease at the sixth month of follow-up can be attributed to axonal loss secondary to direct or indirect effects of PRP treatment.SD OCT is a very valuable tool to document the RNFL thickness changes following the argon laser photocoagulation.

Objective To observe the efficacy of pars plana vitrectomy (PPV) combined with selective retinal photocoagulation (SRP) in the treatment of proliferative diabetic retinopathy (PDR) with vitreous hemorrhage. Methods Two hundred eyes of 190 patients with PDR and vitreous hemorrhage were enrolled in this study.All patients were treated with 23-gauge PPV combined with retinal photocoagulation and intravitreal injection of Lucentis and triamcinolone acetonide.All patients were divided randomly into two groups: the contral group, 108 eyes of 102 cases, received panretinal photocoagulation(PRP) during surgery and the observation group, 92 eyes of 88 cases, received SRP during surgery. All patients were followed up for 6 months.The effect were compared between the two groups. Results BCVA of observation group was better than that of contral group at 1 week, 1 month and 3 months after surgery.The difference was statistically significant(P=0.000). The difference in BCVA was not statistically significant between the two groups at 6 months after surgery(P=0.094). The central macular thickness(CMT) of observation group was lower than that of contral group at 1 week and 1 month after surgery, the difference was statistically significant(P=0.000). The difference was not statistically significant at 3 months after surgery between the two groups(P=0.349). The number of times of retinal photocoagulation in observation group was more than that in contral group.The difference was statistically significant(P=0.000). The incidence of recurrent vitreous hemorrhage and neovascular glaucoma in observation group were higher than those in contral group.The difference were not statistically significant(P=0.526, 0.470). Conclusion Under the auxiliary of anti-vacular endothelial growth factor and triamcinoloneacetonide, microincision vitrectomy with SRP is better than microincision vitrectomy with PRP to treat patients with vitreous hemorrhage and PDR in reducing postoperative macular edema and improve the visual acuity. Key words: Retinopathy, diabetic, proliferative; Vitreous hemorrhage; Vitrectomy, 23-gauge; Photocoagulation, retinal, selective, pan