High-risk Proliferative Diabetic Retinopathy Research Articles

Panretinal photocoagulation for the treatment of proliferative diabetic retinopathy

After the completion of DRS study in 1979, Panretinal Photocoagulation (PRP) became the gold standard for the treatment of proliferative diabetic retinopathy.Light from the laser is absorbed by the retinal pigment epithelium (RPE), and the underlying choroid and it is converted to thermal energy. Those thermal burns denature tissue protein, causing local retinal cell death, coagulative necrosis and eventually scarring. In that respect, laser photocoagulation leads to diminished oxygen demands of the areas of capillary non perfusion, and reduced expression of vasoactive factors such as vascular endothelial growth factor (VEGF) and protein kinase C (PKC) in the retina. As a result, adequate oxygen and nutrients are diverted towards the non‐ischemic retinal areas.As documented by the DRS study, after a 5‐year follow‐up period, the rates of severe visual loss were diminished by at least 50% in all eyes treated with PRP in comparison with untreated control eyes. The greatest beneficial effect was shown for treated eyes with high risk PDR characteristics (any NVD with extent greater than or equal to one‐fourth disc area without vitreous or preretinal hemorrhage, any NVD with vitreous or preretinal hemorrhage,any NVE with extent greater than or equal to one‐half disc area, with vitreous or preretinal hemorrhage). Harmful effects of PRP includes peripheral visual field loss, decrease in visual acuity, nyctalopia etc. Treatment of non‐high risk PDR cases, could also be proposed under certain circumstances such as in patients with difficulty to attend regular appointments, advanced diabetic disease in the fellow eye etc.Although anti‐VEGF agents have been approved for the treatment of PDR, PRP remains an effective therapeutic option and the choice of treatment could be made on an individualized basis. However, in high risk PDR patients with co‐existing maculopathy the addition of anti‐VEGF injections to PRP treatment is advisable.

A Study of the Prevalence of Diabetic Retinopathy in Patients With Ischemic Heart Disease and Diabetes Mellitus.

Background Diabetes mellitus is one of the most important and common chronic diseases worldwide and is expected to increase in prevalence. Diabetic retinopathy (DR) is one of the most prevalent microvascular sequelae of diabetes mellitus (DM), and ischemic heart disease is a macrovascular sequela. This study was conducted to find out the relation between the degree of DR and ischemic heart disease severity in Indian patients. Materials and methods This cross-sectional, descriptive, hospital-based study was conducted in the ophthalmology department at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from September 2022 to June 2024. A total of 200 eyes from 100 patients who were diagnosed with cases of ischemic heart disease and diabetes mellitus were included in the study. Patients with corneal pathology like endothelial dystrophies, corneal degenerations, corneal scars, or trauma preventing good visualization of the posterior segment were excluded from the study. Patients with active uveitis, patients with a history of undergoing any previous vitreoretinal surgery or laser procedures, non-compliant patients, patients not willing to undergo the procedure, or those not consenting to the study were also excluded. Written informed consent was obtained from each patient. Data was entered in Microsoft Exceland statistical analysis was done using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. As the continuous variables showed a skewed distribution, we used the Mann-Whitney test and the Kruskal-Wallis test to test the significance of the difference between continuous and categorical variables. A chi-square test was employed to check the association between categorical variables. Significance was assumed at an alpha error of 5%. Results The prevalence of diabetic retinopathy was found to be 95%. The mean age of patients with DR and patients with no diabetic retinopathy was 58.38 and 59.40 years, respectively, with the majority of the patients being in the age group of 60-69 years (46%). The majority of the patients were males (65%), while 35% were females. There was a significant association between the severity of diabetic retinopathy and the higher HbA1c levels, the use of insulin as a treatment modality, and the higher blood sugar levels in our study population. It was observed that the patients in our study with an ejection fraction of <40% had significantly higher severity of diabetic retinopathy in the form of PDR and high-risk PDR. The severity of the DR was directly correlated with the severity of IHD in our study, with most of the IHD patients with a 40-60% ejection fraction having moderate NPDR and patients with a >60% ejection fraction having mild or moderate NPDR. Conclusion The prevalence of diabetic retinopathy among the IHD patients with diabetes was 95% in our study, with moderate NPDR being the most common stage of DR seen among the patients. It was observed that more severe stages of diabetic retinopathy were seen in patients who were on treatment with insulin than in patients who were on treatment with OHA. Severe stages of diabetic retinopathy were associated with higher blood sugar levels (BSL) and higher glycated hemoglobin levels. In the present study, it was observed that a lower ejection fraction (<40%), which is a marker of reduced cardiac function, was associated with more severe stages of diabetic retinopathy.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage.

To assess the clinical efficacy and safety of combining panretinal photocoagulation (PRP) with intravitreal conbercept (IVC) injections for patients with high-risk proliferative diabetic retinopathy (HR-PDR) complicated by mild or moderate vitreous hemorrhage (VH), with or without diabetic macular edema (DME). Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study. Upon establishing the patient's diagnosis, an initial IVC was performed, followed by prompt administration of PRP. In cases who significant bleeding persisted and impeded the laser operation, IVC was sustained before supplementing with PRP. Following the completion of PRP, patients were meticulously monitored for a minimum of six months. Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography (FFA) results. Therapeutic effect and the incidence of adverse events were observed. Out of 42 patients (74 eyes), 29 were male and 13 were female, with a mean age of 59.17±12.74y (33-84y). The diabetic history was between 1wk and 26y, and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y. The affected eye received 2.59±1.87 (1-10) IVC injections and underwent 5.5±1.02 (4-8) sessions of PRP. Of these, 68 eyes received PRP following 1 IVC injection, 5 eyes after 2 IVC injections, and 1 eye after 3 IVC injections. Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment, with resolution of DME in 51 eyes 3-48wk after initial treatment. A newly developed epiretinal membrane was noted in one eye. Visual acuity significantly improved in 25 eyes. No complications such as glaucoma, retinal detachment, or endophthalmitis were reported. The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

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.

Comparative Analysis of Pain and Duration in Panretinal Photocoagulation: Navilas Laser versus Conventional Laser in Proliferative Diabetic Retinopathy.

To compare the pain perception and treatment duration in patients undergoing panretinal photocoagulation (PRP) for high-risk proliferative diabetic retinopathy (PDR) using Navilas laser versus conventional laser. A study was conducted involving 40 patients with bilateral high-risk PDR. Each patient underwent PRP with conventional laser in one eye and Navilas laser in the other. Laser parameters, including spot size and pulse duration were standardized. Pain perception was evaluated using Verbal Rating Scale (VRS) and Visual Analogue Scale (VAS). The Navilas and conventional laser groups showed no significant differences in baseline visual acuity, lens status, intraocular pressure, cup-to-disc ratio, or cystoid macular edema. The duration of laser treatment was significantly shorter with Navilas laser group (517.3±48.78 seconds, p<0.001). Pain scores (VAS and VRS) were significantly lower in the Navilas laser group (p<0.001, p=0.002 respectively) than in conventional laser group. There was no correlation between VAS and VRS scores and laser time in both the Navilas and conventional laser groups (p>0.05). Utilizing the Navilas laser for PRP in PDR patients offers advantages over conventional lasers, including reduced pain and expedited procedures. These findings contribute valuable insights for optimizing clinical decisions, potentially enhancing patient compliance and minimizing the risk of visual deterioration in diabetic retinopathy treatment.

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.