High-risk Proliferative Diabetic Retinopathy Research Articles

Aflibercept 5+PRN with retinal laser photocoagulation is more effective than retinal laser photocoagulation alone and aflibercept 3+PRN with retinal laser photocoagulation in patients with high-risk proliferative diabetic retinopathy and diabetic macular edema: a 12-month clinical trial.

This study aimed to investigate and compare the efficacy and safety of retinal laser photocoagulation (PRP) alone, PRP with aflibercept 3+PRN, and PRP with aflibercept 5+PRN in patients with both high-risk proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Overall, 170 patients with high-risk PDR and DME (170 eyes from 170 patients) who visited our ophthalmology clinic from December 2018 to December 2020 were divided into the PRP (n=58), aflibercept 5+PRN with PRP (n=53), and aflibercept 3+PRN with PRP (n= 59) groups. General information, such as age, sex, and eye category, was obtained. Moreover, best-corrected visual acuity (BCVA), baseline central macular foveal thickness (CFT), microaneurysm (MA), area of neovascularization (NV), area of hard exudate (HE), and cytokine levels in atrial fluid before and after treatment, were assessed. The χ2 test was used for comparison between groups for statistical data. Analysis of variance was used for the statistical description of measurement data, independent samples were analyzed using Student's t-test, and Student-Newman-Keuls test was used for group comparisons. Differences were considered statistically significant at P < 0.05. After treatment, no significant improvement in the BCVA (logMAR) of patients in the PRP group was observed. The BCVA (log MAR) decreased from 0.72 ± 0.17 and 0.74 ± 0.17 to 0.50 ± 0.13 and 0.53 ± 0.17 in PRP with aflibercept 5+PRN and PRP with aflibercept 3+PRN groups, respectively, with a statistically significant difference compared to those in the PRP group (P<0.05 in all cases). However, no statistically significant difference was observed between the combined treatment groups (P>0.05). The CFT in the PRP-only group decreased slightly from 361.80 ± 36.70 μm to 353.86 ± 40.88 μm, with no statistically significant difference (P>0.05), whereas the CFT in the aflibercept 5+PRN with PRP and aflibercept 3+PRN with PRP groups decreased from 356.57 ± 37.57 μm and 358.17 ± 44.66 μm to 284.87 ± 31.52 μm and 303.19 ± 37.00 μm, respectively, with statistically significant differences before and after treatment (P<0.05 for both groups). Statistically significant differences were observed in CFT between the three groups after treatment (P<0.05 in all cases). The number of MA (pcs) in the PRP, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups decreased from 118.34 ± 27.96, 118.60 ± 33.34, and 116.59 ± 28.95 to 92.95 ± 29.04, 44.60 ± 20.73, and 54.26 ± 25.43, respectively. The two-way comparison of the three groups revealed statistically significant differences in MA (P<0.05 in all cases). In the three groups, NV decreased from 1.00 ± 0.21 mm², 1.01 ± 0.18 mm², and 0.98 ± 0.20 mm² before treatment to 0.49 ± 0.17 mm², 0.31 ± 0.16 mm², and 0.38 ± 0.14 mm², respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, 13, 18, and 18 patients had reduced HE area in the PRP-only, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups, respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, vascular endothelial growth factor, monocyte chemoattractant protein-1, and glial fibrilliary acidic protein levels (pg/mL) in the aqueous humor decreased in both combined treatment groups compared with that at baseline, with statistically significant differences; however, no significant difference was observed between the two combined treatment groups (P>0.05). Aflibercept 5+PRN combined with PRP was safe and effective in treating patients with high-risk PDR and DME, and was more effective than PRP-only and aflibercept 3+PRN with PRP in improving CFT and MA.

Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy With and Without Internal Limiting Membrane Peeling: A Case Series

Introduction : Proliferative Diabetic Retinopathy (PDR) is a potentially blinding complication of diabetes mellitus, one of them because of tractional retinal detachment. Pars Plana Vitrectomy (PPV) is performed to treat it and in recent years internal limiting membrane (ILM) peeling has been employed as an additional treatment for patient with PDR.&#x0D; Case Illustration : Two patient, patient 1 (male, 64 years old) was diagnosed with right eye vitreous hemorrhage due to high-risk PDR and left eye vitreous hemorrhage due to early PDR + DME, and patient 2 (female, 58 years old) was diagnosed with right and left eye PDR + ERM + senile immature cataract. Both patients underwent PPV + membrane peeling + endolaser for both eyes, and additional ILM peeling on their left eye. The visual acuity 1 month after surgery without ILM peeling on right eye was improved to 6/30 and 6/18, and with ILM peeling on left eye was improved to 6/30 for both patients.&#x0D; Discussion : Removal of the ERM either with or without ILM peeling can significantly improve vision. However, many other comparison studies found no functional difference between both groups. In addition, one study found ILM removal was correlated with worse visual outcome. In this study, visual acuity 1 month after surgery in both with and without ILM peeling was improved compared with pre- operative.&#x0D; Conclusion : Although there are still pros and cons, PPV with additional ILM peeling gives results as good as PPV without ILM peeling for patient with PDR.

Proliferative diabetic retinopathy: Role of bevacizumab in decreasing the occurrence of vitreous hemorrhage after panretinal photocoagulation

To investigate the beneficial effect of bevacizumab injection one week prior to panretinal photocoagulation (PRP) on the occurrence of vitreous hemorrhage (VH) following PRP in high-risk proliferative diabetic retinopathy (PDR). This was a case-control pilot study conducted on two groups: an anti-VEGF treatment group, treated with bevacizumab injection one week prior to the first PRP session, and a control group of treatment-naive PDR patients who underwent PRP treatment and were not given an intravitreal bevacizumab injection, consecutively recruited. In both groups, a complete ophthalmological examination was conducted prior to PRP and at 4, 9, and 16 weeks following treatment. The primary endpoint studied was the occurrence of VH. The control group included 69 patients (mean age 63±12.3 years) with high-risk PDR who received PRP treatment only, and the anti-VEGF treatment group included 67 patients (mean age 63.13±10.3 years). None of the demographic variables or comorbidities showed any significant difference between the two groups. The number of PRP sessions was not significantly correlated to the occurrence of VH in either of the groups (P=0.167). Vitreous hemorrhage within 16 weeks following laser treatment occurred in 10 patients (14.5%) in the control group and in only 3 patients (4.5%) in the anti-VEGF group (P=0.047). Our case-control pilot study demonstrates that a bevacizumab injection preceding the initial PRP session might be beneficial in reducing the occurrence of VH in the first 16 weeks following PRP.

Efficacy and safety of pan retinal photocoagulation combined with intravitreal anti-VEGF agents for high-risk proliferative diabetic retinopathy: A systematic review and meta-analysis.

High-risk proliferative diabetic retinopathy (HR-PDR) is the advanced stage of diabetic retinopathy progression with poor prior treatment efficacy and high rates of blindness. This meta-analysis aims to compare the efficacy and safety of pan retinal photocoagulation (PRP) combined with intravitreal anti-vascular endothelial growth factor (aVEGF) (PRP + aVEGF) versus PRP monotherapy in HR-PDR patients. A thorough search was performed through PubMed, Web of Science, EMBASE, and the Cochran Library from inception to December 18, 2022. Outcome measures included change in central macular thickness, best-corrected visual acuity, fluorescein angiography, incidence of undergoing vitrectomy, and adverse events during the follow-up period. Eight studies (6 randomized controlled trials and 2 retrospective studies) with 375 eyes were included in this meta-analysis. There were no obvious differences in the changes of best-corrected visual acuity and fluorescein angiography between the PRP + aVEGF and PRP monotherapy groups. However, PRP + aVEGF group had a significant reduction in the change of central macula thickness (standard mean deviations = -1.44, 95%CI = -2.55 to -0.32, P = .01) and the rate of undergoing vitrectomy (odds ratio = 0.20, 95%CI = 0.05-0.83, P = .01). Additionally, the risks of vitreous hemorrhage and other complications were not significantly different between the 2 groups. Our meta-analysis indicated that PRP + aVEGF might have potential benefits in the treatment of HR-PDR patients. However, given several limitations of this study, more research is needed to confirm our findings.

Retinal vein changes in patients with high-risk proliferative diabetic retinopathy treated with conbercept and panretinal photocoagulation co-therapy: a cohort study.

This study aimed to observe and compare retinal vein diameter changes and other essential indicators in patients with high-risk proliferative diabetic retinopathy (PDR) treated with intravitreal injection of conbercept (IVC) combined with panretinal photocoagulation (PRP) versus PRP monotherapy. A retrospective analysis was conducted on data from patients with high-risk PDR who received specific treatment and were followed up for 24 months. Among 82 patients with high-risk PDR, 50 eyes received PRP combined with IVC, whereas 32 eyes received PRP alone. During the 24-month follow-up period, changes in best-corrected visual acuity (BCVA), central foveal thickness (CFT), retinal vein diameter, number of microaneurysms (MA), neovascularization (NV) area, hard exudate (HE) area, size of the foveal avascular zone (FAZ), superficial capillary plexus (SCP) blood flow density, and adverse effects were recorded and compared between the two groups at baseline and at 6, 12, 18, and 24 months after treatment. The relationship between each observation index and vein diameter was also analyzed. During the 24-month follow up, significant improvements in the BCVA, CFT, retinal vein diameter, number of MAs, NV area, HE area, FAZ, and SCP were observed in the IVC+PRP group after treatment. The PRP group only showed significant reductions in NV and HE areas. The IVC+PRP group showed significant superiority over the PRP group in improving the vein diameter, number of MA, and HE area. However, no statistically significant difference in NV area reduction was found between the groups. In the treatment of high-risk PDR, IVC+PRP therapy has a significant advantage over PRP monotherapy. IVC+PRP therapy may reverse diabetes-induced retinal vein changes, restoring morphology and function.

Infographic: Ranibizumab plus panretinal photocoagulation (PRP) versus PRP alone for high-risk proliferative diabetic retinopathy (PDR): the PROTEUS study

Infographic: Ranibizumab plus panretinal photocoagulation (PRP) versus PRP alone for high-risk proliferative diabetic retinopathy (PDR): the PROTEUS study

Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.

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.

Retinal vein changes after treatment with aflibercept and PRP in high-risk proliferative diabetic retinopathy.

The objective of the study was to investigate the effectiveness of aflibercept and panretinal photocoagulation (PRP) in the treatment of proliferative diabetic retinopathy (PDR). A retrospective analysis was performed on 59 patients (59 eyes) with high-risk PDR who were treated with aflibercept and PRP between January 2018 and December 2019. The best corrected visual acuity (BCVA), central foveal thickness (CFT), and retinal vein diameter post-treatment were compared to those before the treatment. The best corrected visual acuity (BCVA) at 6 months (0.49 ± 0.14 logMAR), 12 months (0.54 ± 0.15 logMAR), 18 months (0.48 ± 0.15 logMAR), and 24 months (0.51 ± 0.15 logMAR) post-treatment were superior to the pre-treatment measurement (0.65 ± 0.18 logMAR). The central foveal thickness (CFT) at 6 months (310.67 ± 52.53 μm), 12 months (295.98 ± 45.65 μm), 18 months (282.56 ± 43.57 μm), and 24 months (281.53 ± 51.16 μm) post-treatment were lower than the pre-treatment measurement (456.53 ± 51.49 μm); the retinal vein diameter at 12 months (310.13 ± 24.60 μm), 18 months (309.50 ± 31.58 μm), and 24 months (317.00 ± 27.54 μm) post-treatment were lower than the pre-treatment measurement (361.81 ± 30.26 μm). Aflibercept intravitreal injection and panretinal photocoagulation may morphologically reverse retinal vein diameter and venous beading in high-risk proliferative diabetic retinopathy.

Optic nerve head perfusion changes in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab or photocoagulation: a randomized controlled trial.

Proliferative diabetic retinopathy (PDR) is a serious sight-threatening disease, and half of the patients with high-risk PDR can develop legal blindness within 5 years, if left untreated. This study was aimed at comparing panretinal photocoagulation (PRP) and intravitreal ranibizumab injections in terms of radial peripapillary capillary (RPC) density on optical coherence tomography angiography (OCTA) in patients with treatment-naive PDR. This open-label, prospective, randomized clinical trial included 50 patients with treatment-naive PDR with optic disc neovascularization and randomized them into two groups: group 1, with patients undergoing two sessions of PRP 2 weeks apart, and group 2, with patients received three intravitreal ranibizumab injections (0.5 mg) 1 month apart for 3 consecutive months. Patients underwent a full ophthalmological examination, including best-corrected distance visual acuity (BCDVA) measurement in the logarithm of minimal angle of resolution (logMAR) notation and OCTA before intervention and monthly after the last laser session or the first intravitreal ranibizumab injection for 3 months of follow-up. Visual field (VF) was tested at the beginning and end of 3 months. Forty-two (84%) eyes completed the 3-month follow-up, including 22 eyes in the PRP group (88%) and 20 (80%) eyes in the ranibizumab group. The two groups were comparable in terms of demographic characteristics, diabetes duration, baseline BCDVA, glycated hemoglobin level, OCTA parameters, VF indices, and intraocular pressure (all P > 0.05). The RPC density change from baseline to the 3-month follow-up was significantly lower in the PRP group than in the ranibizumab group (mean difference in RPC density change: - 3.61%; 95% confidence interval: - 5.57% to - 1.60%; P = 0.001). The median (interquartile range) logMAR change from baseline to the 3-month follow-up (0.0 [0.2]) was significantly higher in the PRP group than in the ranibizumab group (- 0.15 [0.3]; P < 0.05). The median changes in central foveal thickness from baseline to the 3-month follow-up differed significantly between the two groups (P = 0.001). In eyes with PDR and neovascularization of the disc RPC density on OCTA increased in the ranibizumab group and decreased in the PRP group. Visual acuity gain was higher in the ranibizumab group than in the PRP group. Future multicenter trials addressing our limitations are required to verify the findings of this study.

A comparison between the therapeutic effects of Conbercept combined with panretinal photocoagulation and panretinal photocoagulation monotherapy for high-risk proliferative diabetic retinopathy.

To compare the therapeutic effects of the administration of intravitreal Conbercept (IVC) plus panretinal photocoagulation (PRP) to that of PRP monotherapy in patients with high-risk proliferative diabetic retinopathy (PDR). In this retrospective consecutive case series, we analyzed the data on high-risk PDR patients followed up for 12 months. Patients were divided into two groups: the IVC+PRP group and the PRP monotherapy group. Patients in the IVC+PRP group were initially administered 3 IVC injections and PRP, while patients in the PRP monotherapy group received PRP only. Depending on the grouping criteria, patients in both groups were administered either IVC+PRP or PRP only if the neovascularization (NV) did not regress. From the initiation to month 12 of treatment, we recorded and compared the data on the NV regression rate, improvement in best-corrected visual acuity (BCVA), laser spots, changes in central macular thickness (CMT), complications, and the need for vitrectomy for all patients. In this study, 79 eyes of 58 patients in the IVC+PRP group and 86 eyes of 60 patients in the PRP monotherapy group were included. During the follow-up of 12 months, the number of eyes with complete regression, partial regression, and no regression or increase in NV were 56 (70.88%), 23 (29.12%), and 0 (0%) in the IVC+PRP group and 13 (15.12%), 50 (58.14%), and 23 (26.74%) in the PRP group (p < 0.001). The BCVA was significantly higher and CMT was lower in the patients of the IVC+PRP group than in the PRP monotherapy group at 3, 6, and 12 months of follow-up (p < 0.05). The mean number of laser spots was lower in the patients of the IVC+PRP group than in the PRP group (1,453 ± 87 spots vs. 2,267 ± 94 spots, p < 0.05). A significantly lower percentage of patients in the IVC+PRP group underwent vitrectomy than that in the PRP group (7 (8.86%) vs. 27 (31.40%), p < 0.001). High-risk PDR patients treated with IVC + PRP showed a higher rate of NV regression, more effective improvement in the BCVA, and lower vitrectomy rate compared to those who were administered PRP monotherapy.

Comparison of Widefield Laser Ophthalmoscopy and ETDRS Retinal Area for Diabetic Retinopathy

To evaluate agreement of nonmydriatic confocal scanning laser ophthalmoscopy (SLO; EIDON [CenterVue]) and the 7-standard field ETDRS area on ultrawide-field (UWF) SLO imaging for identification of diabetic retinopathy (DR) severity. Single-site, prospective, comparative, instrument validation study. One hundred ten eyes of 55 patients with diabetes mellitus were evaluated. Each patient underwent nonmydriatic, nonsimultaneous stereoscopic imaging using the EIDON camera and 4 fields of 60°× 55° were acquired (macula centered, disc centered, temporal macula, superotemporal). Mydriatic UWF retinal images were acquired using a nonsimultaneous stereographic protocol with UWF imaging (California; Optos plc). Before grading, a standardized ETDRS 7-field image mask was applied to all UWF retinal images. Images from each device were graded independently by 2 masked graders using the ETDRS clinical DR classification. Any discrepancy in DR grading between the devices was adjudicated by a third grader. κ Levels of agreement, sensitivity, and specificity for DR thresholds. Severity by ETDRS grading was as follows: no DR, 10.9%; mild nonproliferative DR (NPDR), 45.5%; moderate NPDR, 16.5%; severe NPDR, 11.8%; proliferative DR, 12.7%; high-risk proliferative DR, 2.7%; and ungradable, 0%. After adjudication, the level of DR identified on EIDON images agreed exactly with that of UWF ETDRS imaging in 87% of eyes (n= 96) and was within 1 step in 99.1% of eyes (n= 109) with a simple κ value of 0.8244 ± 0.0439 (95% confidence interval [CI], 0.7385-0.9104) and weighted (linear) κ value of 0.9041 ± 0.0257 (95% CI, 0.8537-0.9545). Sensitivity and specificity compared with ETDRS field grading for any DR were 0.96 and 0.75, for moderate NPDR or worse were 0.96 and 0.97, and for severe NPDR or worse were 0.91 and 1.00, respectively. Nonmydriatic 4-field stereoscopic widefield imaging using the EIDON device was comparable with the DR severity identified within the ETDRS 7-standard field area of UWF images. Future studies will need to evaluate the applicability of this device as a clinical and research tool and the impact of different widefield coverage areas.

Optical Coherence Tomography Following Panretinal Photocoagulation Demonstrating Choroidal Detachment

Retinal laser therapy such as panretinal photocoagulation can be associated with complications, including rare cases of choroidal detachment. This report describes high-resolution optical coherence tomography (OCT) imaging after retinal laser panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR) demonstrating choroidal detachment. A series of three sequential patients with high-risk proliferative diabetic retinopathy who were PRP laser naïve were examined with spectral-domain OCT immediately after green solid-state laser or PASCAL® PRP treatment. All three patients demonstrated a significant choroidal detachment immediately after PRP treatment. By one month after PRP, the choroidal detachment resolved spontaneously in all patients. OCT examinations were performed to detect and evaluate the severity and the change of choroidal detachment and thickness measurements were quantified and demonstrated a mean decrease in choroidal thickness of 122 µm (p &lt; 0.05 in all patients). Conventional green solid-state laser and PASCAL® laser both have the risk of developing complications such as choroidal detachment. While the rate of choroidal detachment has been reported to be quite low, this could be due to subclinical, self-limited, choroidal detachments. The risk could be larger than previously reported using modern high-resolution clinical optical imaging such as OCT.

Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy

To evaluate the ability of capillary nonperfusion parameters on OCT angiography (OCTA) to predict the development of clinically significant outcomes in eyes with referable nonproliferative diabetic retinopathy (NPDR). Prospective longitudinal observational study. In total, 59 patients (74 eyes) with treatment-naive moderate and severe (referable) NPDR. Patients were imaged with OCTA at baseline and then followed-up for 1 year. We evaluated 2 OCTA capillary nonperfusion metrics, vessel density (VD) and geometric perfusion deficits (GPDs), in the superficialcapillary plexus, middle capillary plexus (MCP), and deep capillary plexus (DCP). We compared thepredictive accuracy of baseline OCTA metrics for clinically significant diabetic retinopathy (DR) outcomes at1year. Significant clinical outcomes at 1 year, defined as 1 or more of the following-vitreous hemorrhage, center-involving diabetic macular edema, and initiation of treatment with pan-retinal photocoagulation or anti-VEGF injections. Overall, 49 patients (61 eyes) returned for the 1-year follow-up. Geometric perfusion deficits and VD in the MCP and DCP correlated with clinically significant outcomes at 1 year (P < 0.001). Eyes with these outcomes had lower VD and higher GPD, indicating worse nonperfusion of the deeper retinal layers than those that remained free from complication. These differences remained significant (P= 0.046 to < 0.001) when OCTA parameters were incorporated into models that also considered sex, baseline corrected visual acuity, and baseline DR severity. Adjusted receiver operating characteristic curve for DCP GPD achieved an area under the curve (AUC) of 0.929, with sensitivity of 89% and specificity of 98%. In a separate analysis focusing on high-risk proliferative diabetic retinopathy outcomes, MCP and DCP GPD and VD remained significantly predictive with comparable AUC and sensitivities to the pooled analysis. Evidence of deep capillary nonperfusion at baseline in eyes with clinically referable NPDR can predict short-term DR complications with high accuracy, suggesting that deep retinal ischemia has an important pathophysiologic role in DR progression. Our results suggest that OCTA may provide additional prognostic benefit to clinical DR staging in eyes with high risk.

Do different lipid components accelerate the pathogenesis and severity of Diabetic Retinopathy?

BackgroundTo assess the association of lipid and lipid-derived toxic molecules in pathogenesis and severity of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM).MethodsThe present cross-sectional study included 14 healthy individuals (HC) without T2DM, 22 T2DM subjects without DR (DNR), 24 T2DM subjects with mild non-proliferative DR (MNPDR), and 24 T2DM subjects with high-risk proliferative DR (HRPDR). All subjects underwent plasma and vitreous analysis for estimation of total lipid (TL), free fatty acid (FFA), lipid peroxides (LPOs) like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE), the advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY) and vascular endothelial growth factor (VEGF) following standard spectrophotometric and enzyme-linked immunosorbent assay (ELISA) methods respectively.ResultsThe concentration of TL, FFA, markers of lipid peroxidation and lipoxidation as well as VEGF in plasma and vitreous were found to be significantly elevated stepwise inT2DM subjects (HRPDR > MNPDR > DNR) compared to healthy controls (HC).Further, plasma conventional lipid components like total cholesterol (TCH), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), FFA and TL showed their significant positive correlations with vitreous level of different LPOs, ALE and VEGF in the DR group.ConclusionTotal lipid and lipid-derived detrimental biomolecules ultimately result in increased secretion of VEGF and thus not only add as associated mediators in the pathogenesis of DR, these also accelerate the severity of microangiopathy in T2DM.

Vitreomacular Interface Disorders in Proliferative Diabetic Retinopathy: An Optical Coherence Tomography Study.

Vitreomacular interface plays an important role in the pathogenesis and progression of proliferative diabetic retinopathy (PDR). This study investigated the prevalence and risk factors of vitreomacular interface disorders (VMID) in PDR. The macular optical coherence tomography (OCT) scans of 493 eyes from 378 PDR patients were retrospectively reviewed to detect VMID, including vitreomacular adhesion (VMA), vitreomacular traction (VMT), epiretinal membrane (ERM), lamellar hole–associated epiretinal proliferation (LHEP), and macular hole (MH). The associations between VMID and baseline factors, intraretinal structure, and visual acuity were analyzed. The prevalence was 78.9% for ERM, 13.4% for VMT, 4.8% for MH, 2.2% for LHEP, and 2.0% for VMA, respectively. On multivariable analyses (odds ratio, 95% confidence interval), fibrovascular proliferation (FVP) was positively associated with MH (8.029, 1.873–34.420), VMT (3.774, 1.827–7.798), and ERM (2.305, 1.460–3.640). High-risk PDR was another risk factor of ERM (1.846, 1.101–3.090). Female gender was positively associated with MH (3.836, 1.132–13.006), while vitreous hemorrhage was negatively associated with MH (0.344, 0.133–0.890). Eyes with all VMID subtypes showed more frequent macular cysts and tractional retinal detachment with poorer visual acuity (p ≤ 0.001). Therefore, the prevalence of VMID was considerably high, indicating that this distinct entity should be considered in interventions for PDR.

Role of EPO and TCF7L2 Gene Polymorphism Contribution to the Occurrence of Diabetic Retinopathy.

Objective: For studying the association of EPO (rs551238), EPO (rs1617640), and TCF7L2 (rs7903146) gene with diabetic retinopathy in Northern Chinese population. Methods: We conducted a case-control study, which enrolled 680 subjects and performed SNP genotyping and calculated allele frequencies. Results: When comparison was performed between DR patients and normal persons, the EPO (rs551238) AA genotype has a significant risk association with DR, and AC genotype has a significant protective association with DR. The EPO (rs551238) A allele has a significant risk association with DR, and C allele has a significant protective association with DR. When comparison was performed between DR patients and DM patients, the EPO (rs551238) CC genotype has a significant protective association with DR; the EPO (rs551238) A allele has a significant risk association with DR; and C allele has a significant protective association with DR. When comparison was performed between DR patients and normal persons, the EPO (rs1617640) GT genotype has a significant protective association with DR, and TT genotype has a significant risk association with DR. The EPO (rs1617640) G allele has a significant protective association with DR, and T allele has a significant risk association with DR. In addition, we found that TT genotype does not exist in rs7903146 of TCF7L2 in Chinese population so that the data could not be used. Conclusions: EPO (rs551238, rs1617640) genotype is a susceptible gene for DR in Chinese type 2 diabetic patients, especially the high-risk PDR.

Progression to Vision-Threatening Retinopathy Complications Following Panretinal Laser for Proliferative Diabetic Retinopathy.

To report the time in which patients with panretinal photocoagulation (PDR) progress to vision-threatening retinopathy (VTR) complications after receiving PRP, and risk factors in routine clinical practice. Records of patients with complete PRP for PDR were retrospectively reviewed for up to 3.5 years after PRP. Two hundred twenty eyes were selected. Time from PRP to VTR was 1.25 ± 0.82 years. Age, Black race, neovascularization of the disc on examination, diabetic foot disease (DFD), and high-risk PDR characteristics on fluorescein angiography were identified as significant risk factors. Half of patients with DFD on examination developed a VTR within 1.5 years after PRP (P < .001). In clinical practice, providers may consider DFD and Black race as predictors of time to VTR event within 4 years after PRP in patients with PDR. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):186-193.].

Assessment of Diabetic Choroidopathy Using Ultra-Widefield Optical Coherence Tomography.

PurposeThe purpose of this study was to investigate a confocal scanning laser ophthalmoscopy (cSLO) ultra-widefield (UWF) swept-source optical coherence tomography (S-SOCT) in assessment of diabetic choroidopathy and to evaluate the agreement of measurements with a spectral-domain OCT (SD-OCT) instrument.MethodsWe conducted a cross-sectional study of patients with diabetes evaluating the choroidal vascularity index (CVI) in the nasal, temporal, and central macula segments of a UWF SS-OCT scan centered to the fovea. UWF pseudocolored fundus images were used for diabetic retinopathy (DR) severity staging. The CVI values were compared between different degrees of severity of DR and different posterior-pole sectors with linear mixed models. Central macula CVI measurements were repeated on SD-OCT scans; the interobserver intraclass coefficient (ICC) was calculated between SS-OCT and SD-OCT.ResultsA total of 151 eyes of 85 patients were included. The CVI values decreased from nonproliferative DR to proliferative DR, with high-risk proliferative DR having significantly lower CVI values than moderate to severe nonproliferative DR (P = 0.03). The central macula region was the most evidently affected; the nasal sector was the least affected. The agreement between SS-OCT and SD-OCT was moderate (ICC = 0.50).ConclusionsDiabetic choroidopathy progresses with worsening of DR toward proliferative disease; choroidal depletion is more prominent in the macula. Caution is recommended in comparing CVI values between different devices.Translational RelevanceChoroidal vascularity informs about the severity of DR and its complications, such as macular edema. The agreement between readers and between instruments may be suboptimal in certain cases.

English

BACKGROUND Diabetic retinopathy is becoming one of the common blinding disease in the world affecting people in both developing and developed countries.Basic mechanism thought to be of advanced glycation end products and othertoxic mediators causingtissue destruction and pathological process. Antioxidants have a major role in preventing this pathological process. Among various antioxidants some of the common blood products have thought to have a role. One among them is serum bilirubin. This study is done to know the correlation of diabetic retinopathy and serum bilirubin levels and thus know its importance in future in preventing progression of this blinding disease. METHODS A cross sectional study was done among OPD patients with type 2 diabetes for a period of one year. Inclusion criteria were diagnosed cases of type 2 diabetes for more than 1 year and age above 40 years. Exclusion criteria included all systemic diseases/drugs affecting liver function tests, confounding factors affecting serum bilirubin levels, extremely poor glycemic control and subjects in whom fundus was not visible due to media opacities excluding causes linked with diabetic retinopathy. After taking consent, detailed history and ophthalmic evaluation, venous blood was drawn and sent for serum bilirubin analysis. Diabetic retinopathy was classified according to ETDRS classification. Statistical study was done after compiling data. RESULTS Among the study subjects – 38.2% were diabetics. Common age group was 51 to 60 years with incidence of diabeties more in males 64.3%. Among diabetic retinopathy noted– mild NPDR was 31%, moderate NPDR was 35.7%, severe NPDR was 11.9%, very severe NPDR was 4.8% and PDR was 16.6 % respectively. The mean serum total bilirubin levels in non DR was 0.597 ± 0.17, mild NPDR was 0.4 ± 0. 15, moderate NPDR was 0.36 ±0.12, severe NPDR was 0.36±0.17, very severe NPDR was 0.35±0.07, low risk PDR was 0.3±0.10 and high risk PDR was 0.32±0.15 respectively. CONCLUSIONS This study concluded that severity of diabetic retinopathy was inversely proportional to the total, direct and indirect serum bilirubin levels. KEY WORDS Diabetic Retinopathy, Serum Bilirubin, Diabetes Mellitus, ETDRS

Fast Progression to Proliferative Diabetic Retinopathy

Purpose. This case report illustrates rapid progression of diabetic retinopathy in a patient with poor compliance to diabetic management. It additionally demonstrates the utility of panoramic/ultra-wide field retinal imaging in assessing diabetic retinopathy progression. Material and Methods. A 42-year-old female patient was examined seven times over a 25 month period at a private ophthalmology/optometry practice with dilated fundus examinations. Fundus images were obtained using a pano- ramic/ultra-widefield laser retinal imager. Fluorescein angio- graphy (FA) was performed to assess for diabetic macular edema (DME), retinal ischemia and neovascularization, and laser photocoagulation was conducted as indicated by the clinical picture. Ophthalmic ultrasonography was performed to confirm tractional retinal detachments (TRD) at the final visit. Results. Initially, visual acuity was adequate (20/30; 6/9; LogMAR 0.18 in each eye) and the patient was diagnosed with moderate non-proliferative diabetic retinopathy. Diffuse leakage resulting in DME, confirmed with FA at the second visit, was treated with focal laser photocoagulation. However, after being lost to follow-up for over a year, her vision had deteriorated severely to finger counting at 1ft (30.5 cm) in the right eye, and 20/400; 6/120; LogMAR 1.30 in the left: the result of high-risk proliferative diabetic retinopathy in each eye. The patient underwent three treatments of pan-retinal photocoagulation (PRP), but she nevertheless developed tractional retinal detachments (TRD) in both eyes. Conclusion. The combination of poorly controlled diabetes and poor compliance with follow-up care in diabetic retino- pathy can lead to rapid progression of retinopathy and blind- ness. Early detection of diabetic retinopathy with panoramic/ ultra-wide field retinal imaging allows for appropriate staging and management of the disease, and ultimately, better visual outcomes. Keywords Diabetic retinopathy, proliferative diabetic retinopathy, panoramic retinal imaging, ultra-wide field retinal imaging, pan-retinal photocoagulation, tractional retinal detachment