Treatment Of Proliferative Diabetic Retinopathy Research Articles

Increased Expression of Growth Hormone–Releasing Hormone in Fibrinous Inflammation of Proliferative Diabetic Retinopathy

To investigate the involvement of growth hormone-releasing hormone (GHRH) - growth hormone (GH) signaling in pathogenesis of proliferative diabetic retinopathy (PDR). Experimental laboratory study. Vitreous humor, aqueous humor, and serum were obtained from 36 eyes of 36 patients with or without type 2 diabetes from 2017 to 2019. For histologic examination, 6 fibrovascular membranes were excised from eyes with active PDR. Three fibrovascular membranes were excised from nondiabetic patients with proliferative vitreoretinopathy (PVR) as controls. In PDR, the fibrovascular tissues consisted of a mature region containing fibrocytes, and an immature region populated by abundant polymorphonuclear leukocytes in a fibrinogen meshwork. Clusters of leukocytes were found adhering to the vascular walls. In PVR, no fibrinogen and polymorphonuclear leukocyte was observed in the fibrovascular membranes. The levels of GHRH and GH in PDR were significantly increased (P < .001), with 1.8-fold and 72.8-fold in vitreous humor, and 2-fold and 4.9-fold in aqueous humor, respectively, when compared with corresponding levels in controls. No significant difference was detected for insulin-like growth factor-1. Immunohistochemistry showed intense expression of GHRH and its receptor GHRH-R in polymorphonuclear leukocytes, vascular endothelial cells, and fibrocytes in fibrovascular membranes of PDR. GHRH staining was not detectable in infiltrating cells within the fibrovascular membrane of PVR. These findings reveal a possible involvement of GHRH/GHRH-R in fibrinous inflammation that might contribute to the formation of fibrovascular membrane in PDR through mediating activities of leukocytes, vascular endothelial cells, and fibrocytes. Targeting GHRH/GHRH-R may be considered as a potential therapeutic approach for the treatment of PDR.

Visual Field Changes Over 5 Years in Patients Treated With Panretinal Photocoagulation or Ranibizumab for Proliferative Diabetic Retinopathy

Preservation of peripheral visual field (VF) is considered an advantage for anti-vascular endothelial growth factor agents compared with panretinal photocoagulation (PRP) for treatment of proliferative diabetic retinopathy. Long-term data on VF are important when considering either treatment approach. To further evaluate changes in VF throughout 5 years among eyes enrolled in the Protocol S clinical trial, conducted by the DRCR Retina Network. Post hoc analyses of an ancillary study within a multicenter (55 US sites) randomized clinical trial. Individuals with eyes with proliferative diabetic retinopathy enrolled in Protocol S were included. Data were collected from February 2012 to February 2018. Analysis began in June 2018. Panretinal photocoagulation or intravitreous injections of 0.5-mg ranibizumab. Diabetic macular edema, whenever present, was treated with ranibizumab in both groups. Panretinal photocoagulation could be administered to eyes in the ranibizumab group when failure or futility criteria were met. Mean change in total point score on VF testing with the Humphrey Field Analyzer 30-2 and 60-4 test patterns. Of 394 eyes enrolled in Protocol S, 234 (59.4%) were targeted for this ancillary study. Of these, 167 (71.4%) had VF meeting acceptable quality criteria at baseline (median [interquartile range] age, 50 [43-58] years; 90 men [53.9%]). At 5 years, 79 (33.8%) had results available. The mean (SD) change in total point score in the PRP and ranibizumab groups was -305 (521) dB and -36 (486) dB at 1 year, respectively, increasing to -527 (635) dB and -330 (645) dB at 5 years, respectively (P = .04). After censoring VF results after PRP treatments in the ranibizumab group, the 5-year mean change in total point score was -201 (442) dB. In a longitudinal regression analysis of change in total point score including both treatment groups, laser treatment was associated with a mean point decrease of 208 (95% CI, 112-304) dB for the initial PRP session, 77 (95% CI, 21-132) dB for additional PRP sessions, and 325 (95% CI, 211-439) dB for endolaser. No association was found between change in point score and the number of ranibizumab injections during the previous year (-9 per injection [95% CI, -22 to 3]). The limited data available from Protocol S suggest that there are factors besides PRP associated with VF loss in eyes treated for proliferative diabetic retinopathy. Further clinical research is warranted to clarify the finding. ClinicalTrials.gov identifier: NCT01489189.

Mining the proliferative diabetic retinopathy-associated genes and pathways by integrated bioinformatic analysis.

Diabetic retinopathy (DR) especially proliferative diabetic retinopathy (PDR) is a serious eye disease. We aimed to identify key pathway and hub genes associated with PDR by analyzing the expression of retinal fibrovascular tissue in PDR patients. First raw data were downloaded from the Gene Expression Omnibus database. Median normalization was subsequently applied to preprocess. Differentially expressed genes (DEGs) analyzed with the Limma package. Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network for all genes. Then, we compared the DEGs and modules filtered out by WGCNA. A protein-protein interaction network based on the STRING web site and the Cytoscape software was constructed by the overlapping DEGs. Next, the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Finally, we used the Comparative Toxicogenomics Database to identify some important pathways and hub genes tightly related to PDR. Functional enrichment analysis showed that the pathway of cytokine-cytokine receptor interaction was significantly related to PDR eight hub genes which were associated with pathway including tumor necrosis factor (TNF), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A), C-C chemokine 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), oncostatin M (OSM) interleukin 10 (IL10), interleukin 15 (IL 15), and interleukin 1B (IL1B). We identified one pathway and eight hub genes, which were associated with PDR. The pathway provided references that will advance the understanding of mechanisms of PDR. Moreover, the hub genes may serve as therapeutic targets for precise diagnosis and treatment of PDR in the future.

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

American Society of Retina Specialists Clinical Practice Guidelines on the Management of Nonproliferative and Proliferative Diabetic Retinopathy without Diabetic Macular Edema.

Nonproliferative (NPDR) and proliferative diabetic retinopathy (PDR) without diabetic macular edema (DME) affect millions of individuals living with diabetes throughout the world. There is increasing data on various management strategies for such patients, but there is limited consensus on how the data should be adopted into clinical practice. This literature review and editorial presents and synthesizes the current evidence for various management paradigms for NPDR and PDR without DME. Retina specialists are an integral member of the diabetes management team, and should encourage patients on the importance of glycemic and cardiovascular optimization for both systemic and retinopathy risk factor reduction. The diabetic retinopathy severity scale (DRSS) is now an approvable endpoint for clinical trials in the United States, therefore becoming more clinically relevant. For PDR without DME, the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy Study (ETDRS) established the standard of care with panretinal photocoagulation (PRP). Laser parameters have since evolved to include less intense and earlier intervention. Studies have recently demonstrated that anti-vascular endothelial growth factor (VEGF) treatment of PDR is effective at regressing neovascularization and improving DRSS levels in many patients. Further evidence is required to determine optimal treatment frequency, duration, and retreatment criteria, in the real world. There are concerns for adverse events in patients being lost to follow up during anti-VEGF treatment. For NPDR without DME, the standard of care has been a wait-and-watch approach. Data within the DRS and the ETDRS suggest that PRP for severe NPDR can be an option for select patients as well. Multiple clinical trials have now demonstrated that anti-VEGF treatment can improve the DRSS score in NPDR. Further studies are required to assess whether this positively affects long-term visual outcomes, and whether the benefits outweigh the risks in the real world for routine use. There is cumulative evidence demonstrating the efficacy of various treatment options for NPDR and PDR without DME. Currently, patients would most likely benefit from thoughtful management strategies that are tailored to the individual patient.

Peripapillary retinal nerve fiber layer thickness changes after panretinal photocoagulation and its relation with visual acuity changes in patients with diabetic retinopathy

Background: Panretinal photocoagulation (PRP) is currently the main treatment for proliferative diabetic retinopathy. Optical coherence tomography (OCT) is a noninvasive method of analyzingin vivo retinal architecture. Objectives: The objective was to evaluate the effect of PRP on peripapillary retinal nerve fiber layer thickness (RNFLT) in patients with diabetic retinopathy using OCT and to correlate peripapillary RNFLT changes with the changes in visual acuity (VA). Materials and Methods: This is a prospective study including eighty eyes of eighty patients with proliferative diabetic retinopathy (PDR) and severe non-PDR. PRP was done with frequency-doubled Nd: YAG (532 nm) laser. Peripapillary RNFLT was measured by spectral-domain OCT at baseline and 6 months post-PRP and assessed using paired t-test. The baseline VA and changes in VA 6 months post PRP were recorded. The relationship between RNFL loss and changes in VA was assessed using ANOVA and independent t-test. Results: The mean age of the patients was 60 years, with 65% of males and 35% of females. At 6 months post-PRP, there was a significant reduction in average RNFLT with a reduction in all quadrants, except in the temporal quadrant. According to interval changes of VA, the patients were divided into improved (22.5%), unchanged (48.8%), or worsened (28.7%) groups. Improved VA group showed a significant decrease in peripapillary RNFLT. Conclusion: RNFLT reduction following PRP can be due to axonal loss secondary to the direct or indirect effects of PRP. The extremely mild reduction in the temporal quadrant can be due to the sparing of papillomacular bundle during laser treatment.

Intravitreal injection of Conbercept-assisted vitrectomy for the treatment of proliferative diabetic retinopathy and its effects on inflammatory factors and ANGPTL4 in the vitreous

Intravitreal injection of Conbercept-assisted vitrectomy for the treatment of proliferative diabetic retinopathy and its effects on inflammatory factors and ANGPTL4 in the vitreous

Comparison of efficacy between 27G and 25G vitrectomy for proliferative diabetic retinopathy

Objective To compare the efficacy between 27G and 25G vitrectomy for the treatment of proliferative diabetic retinopathy (PDR). Methods The data of 185 eyes of 185 cases of PDR who received vitrectomy in this hospital from Jan. 2017 to Dec. 2017 were analyzed retrospectively. All cases were divided into two groups. There were 64 eyes in the 27G vitrectomy group and 121 eyes in the 25G vitrectomy group. Results There was no significant difference in the preoperative baseline data between the two groups (P>0.05). The difference of postoperative score of symptoms, operation time, intraocular pressure, reoperation rate because of retinal detachment and vitreous hemorrhage were all not statistically significant between the two groups(P=0.070, 0.367, 0.503, 0.667). Conclusion 27G and 25G are equally safe and effective in the treatment of diabetic retinopathy. Key words: Retinopathy, diabetic, proliferative; Vitrectomy, 25G, 27G; Visual acuity

Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy.

To investigate whole transcriptional differences between proliferative diabetic retinopathy (PDR) neovascular membranes (NVMs) and retinas, and the regulatory genes participating in retinal neovascularization in PDR. We used high-throughput sequencing technology to capture the whole-genome gene expression levels of all participants, including 23 patients with PDR or branch retinal vein occlusion (BRVO), 3 normal retinal samples, and 2 retinal samples from type II diabetic (T2D) eyes by donation, followed by analyses of expression patterns using bioinformatics methods, then validation of the data by in situ hybridization and Western blotting. We showed that transcriptional profiles of the NVMs were distinct from those of the retinas. Angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2, and their receptors FLT4, TIE1, TIE2, and EPHB4, respectively, were overexpressed. Expression of VEGFA was highly upregulated in T2D retina, but low in the NVMs, while angiogenesis transcription factors, including ETS1 and ERG, were coordinately upregulated in NVMs. This study described a PDR neovascularization model in which pathological retina-secreted vascular endothelial growth factor A (VEGFA) enhanced the expression of a set of angiogenesis transcription factors and growth factors, to cooperatively induce the retinal neovascularization. Based on these results, novel potential therapeutic targets and biomarkers for PDR treatment and diagnosis are suggested.

Upregulation of Lysyl Oxidase Expression in Vitreous of Diabetic Subjects: Implications for Diabetic Retinopathy.

Animal studies have shown diabetes-induced lysyl oxidase (LOX) upregulation promotes blood-retinal-barrier breakdown and retinal vascular cell loss associated with diabetic retinopathy (DR). However, it is unclear whether changes in LOX expression contribute to the development and progression of DR. To determine if vitreous LOX levels are altered in patients with DR, 31 vitreous specimens from subjects with advanced proliferative DR (PDR), and 27 from non-diabetics were examined. The two groups were age- and gender-matched (57 ± 12 yrs vs. 53 ± 18 yrs; 19 males and 12 females vs. 17 males and 10 females). Vitreous samples obtained during vitrectomy were assessed for LOX levels using ELISA. LOX was detected in a larger number of PDR subjects (58%) than in non-diabetic subjects (15%). Additionally, ELISA measurements showed a significant increase in LOX levels in the diabetic subjects with PDR, compared to those of non-diabetic subjects (68.3 ± 112 ng/mL vs. 2.1 ± 8.2 ng/mL; p < 0.01). No gender difference in vitreous LOX levels was observed in either the diabetic or non-diabetic groups. Findings support previous reports of increased LOX levels in retinas of diabetic animals and in retinal vascular cells in high glucose condition, raising the prospect of targeting LOX overexpression as a potential target for PDR treatment.

Surgical Innovations in the Treatment of Diabetic Macular Edema and Diabetic Retinopathy.

Diabetic macular edema (DME) and complications of proliferative diabetic retinopathy (PDR) are the primary causes of vision loss in patients with diabetic retinopathy. As the incidence of diabetes increases worldwide, new, cost-effective treatments for DME and PDR will become paramount. Currently, anti-vascular endothelial growth factor (anti-VEGF) medications are considered first-line treatment. However, multiple visits for injections and the economic and time burden they entail make this treatment modality less than ideal. Early vitrectomy as well as depot delivery systems for medications could potentially reduce the treatment burden of patients with diabetes, prevent visual loss, and provide long-term stabilization of retinopathy in patients with diabetes. Newer port delivery systems for anti-VEGF medications could oneday make this treatment modality better suited for patients across the globe. Real-world data shows poor compliance with treatment among patients with diabetes. Recent publications show catastrophic results when anti-VEGF treatments are stopped abruptly. The port delivery system for ranibizumab shows maintenance of adequate anti-VEGF levels in the vitreous cavity for many months. Early vitrectomy can provide cost-effective long-term stabilization in eyes with diabetic retinopathy. Microincisional vitrectomy as a treatment for DME and PDR remains controversial and larger trials are needed to definitively prove its superiority over other modalities; however, small-scale data point towards its usefulness in specific populations. Newer port delivery systems of anti-VEGF show promise in decreasing the number of office visits in patients with diabetic retinopathy.

Influence of Baseline Macular Edema on Cost Evaluation of Panretinal Photocoagulation vs Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy

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.

Modern optimizing techniques of surgical treatment of proliferative diabetic retinopathy

Aim. To evaluate the clinical efficacy of microinvasive vitrectomy and three-dimensional digital imaging in patients with proliferative diabetic retinopathy.&#x0D; Methods. The clinical treatment results were studied in 62 patients (62 eyes) with proliferative diabetic retinopathy complicated by tractional retinal detachment who underwent vitreoretinal surgery with the use of microinvasive techniques and three-dimensional digital imaging. There were 38 (61%) women, 24 (39%) men, mean age 57±5.2 years. The duration of diabetes mellitus was 6 to 13 years (an average of 11.7 years). Of the 62 patients, 11 had insulin-dependent diabetes mellitus, and 51 had non-insulin-dependent diabetes.&#x0D; Results. Final anatomical result (the elimination of the zones of proliferation and adhesion of the retina) was reached in 59/62 (95.1%) of the eyes: in 54/62 (87%) eyes after the first intervention, in 8/62 eyes after additional surgical intervention. The maximum corrected visual acuity increased in 55/62 (88.7%) eyes from 0.01±0.12 to 0.22±0.11 (p &lt;0.05); in 3/62 (4.8%) eyes remained the same; 4/62 (6.5%) eyes had visual impairment. Complications were diagnosed in 14 (22.6%) of the eyes: retinal tears (10), hemophthalmus (2), subchoroid hemorrhage (1), detachment of the choroid (1). Postoperative control of intraocular pressure demonstrated the following: 36 (58.1%) eyes had normal intraocular pressure (11–22 mm Hg), 20 (32.3%) — increased intraocular pressure (≥22 mm Hg), 6 (9.7%) — reduced intraocular pressure (≤10 mm Hg). In the postoperative period (up to 1 month after surgery) additional surgical interventions were performed on 8/62 (12.9%) eyes.&#x0D; Conclusion. In patients with proliferative diabetic retinopathy, the use of microinvasive vitreoretinal technologies and digital imaging system provide high anatomical (95.1% of patients) and functional results (88.7% of patients).

Frequency and Risk Factors for Neovascular Glaucoma After Vitrectomy in Eyes with Diabetic Retinopathy: An Observational Study.

IntroductionVitrectomy is one of the main treatments for proliferative diabetic retinopathy (PDR). Postoperative neovascular glaucoma, in which it is difficult to obtain satisfactory results using conventional filtering surgery, is one of the most serious complications of vitrectomy. It often requires destructive surgery, such as ciliary body photocoagulation or freezing, and the outcome with regard to visual acuity (VA) is extremely poor. The purpose of this study was to evaluate the prevalence of neovascular glaucoma (NVG) after modern vitrectomy techniques and investigate how variables assessed before and after vitrectomy are associated with patients who develop NVG after PDR surgery.MethodsThis was an observational study including the medical records of patients who underwent vitrectomy for PDR at Tianjin Eye Hospital from June 2014 to July 2016, were followed for at least 24 months postoperatively, and NVG developed within 2 years after surgery was recorded. Each patient underwent complete preoperative ophthalmic examinations in both preoperative and follow-up appointments. Factors associated with survival were determined using the Kaplan–Meier (KM) survival analysis to calculate the incidence of NVG after vitrectomy for PDR. Multivariable analysis was performed with the Cox regression proportional hazards model to verify the results of the analysis and eliminate interference factors between variables. All statistical analyses were performed using R statistical software (http://www.r-project.org) for Windows.ResultsIn all, 238 patients (238 eyes) fulfilled the study criteria. NVG occurred in 11 of 238 eyes (4.6%). The percentages of NVG development after vitrectomy at 6, 12, and 24 months were 0.42%, 3.3%, and 4.6%, respectively. After step analysis, multivariable regression identified preoperative high intraocular pressure (IOP) combined with retinal vein occlusion (RVO), severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels as significant predictors of NVG.ConclusionPreoperative high IOP combined with RVO, severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels are significant predictors of NVG after vitrectomy.

Association of vitreous vitamin C depletion with diabetic macular ischemia in proliferative diabetic retinopathy.

PurposeVitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.MethodsThis prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).ResultsPDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).ConclusionsVitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.

The efficacy of vitrectomy combined with conbercept in the treatment of diabetic retinopathy

Objective To evaluate the clinical efficacy of vitrectomy combined with intravitreal injection of conbercept in the treatment of proliferative diabetic retinopathy (PDR). Methods A prospective control study. The data of 86 eyes of 62 patients with PDR from Oct. 2016 to Dec. 2017 were analyzed. All cases were divided into two groups. The control group, 41 eyes of 31 cases, underwent vitrectomy only. The combined group, 45 eyes of 31 cases, underwent vitrectomy combined with intravitreal injection of conbercept. BCVA, macular area retinal thickness and central macular thickness(CMT) were measured before and 3, 6 months after surgery. The complications were recorded. Results The total effective rate of the combined group was better than that of the control group(95.56% vs 75.61%), the difference was statistically significant (χ2=5.5444, P=0.0185). BCVA (LogMAR) of the combined group were 1.13±0.19, 0.71±0.22 and 0.38±0.16 before and 3, 6 months after surgery. BCVA of control group was 1.12±0.18, 0.73±0.20 and 0.53±0.18, respectively. BCVA at 6 months after surgery in the combined group was better than that in the control group (t=4.091, P=0.0001). The differences in CMT, macular retinal thickness and postoperative complications were not significant between the two groups (P>0.05). Conclusion Vitrectomy combined with intravitreal injection of conbercept for the treatment of PDR is effective. Key words: Retinopathy, diabetic, proliferative; Vitrectomy; Conbercept; Visual function; Central macular thickness

Curcumolide, a unique sesquiterpenoid from Curcuma wenyujin displays anti-angiogenic activity and attenuates ischemia-induced retinal neovascularization

BackgroundTargeting vascular endothelial growth factor is a common treatment strategy for neovascular eye disease, a leading cause of visual impairment and blindness. However, these approaches are limited or carry various complications. Therefore, there is an urgent need for the development of unique therapeutic approaches. PurposeTo investigate the anti-angiogenic effects of curcumolide and its mechanism of action. Methods /Study designsIn this study, we examine the effects of curcumolide on the process of vasculature formation, including cell proliferation, migration, tube formation and apoptosis in vitro using human umbilical vascular endothelial cells (HUVECs). We also assess the anti-angiogenic effects of curcumolide in vivo using a mouse model of oxygen induced retinopathy (OIR). The mechanism of anti-angiogenic effects was investigated by measuring the expression level of various signaling proteins and the molecular docking simulations. ResultsIntravitreal injection of curcumolide reduced the formation of retinal neovascular tufts and VEGFR2 phosphorylation in the murine OIR model at concentrations administered without definite cellular and retinal toxicities. Curcumolide suppressed VEGF-induced HRMECs proliferation, migration and tube formation in a dose-dependent manner. Meanwhile, it promoted caspase-dependent apoptosis. Curcumolide also inhibited VEGF-induced phosphorylation of VEGFR-2 tyrosine kinase, and suppressed downstream protein kinases of VEGFR2, including Src, FAK, ERK, AKT, and mTOR in HRMECs. In silico study revealed that curcumolide bound with ATP-binding sites of the VEGFR2 kinase unit by the formation of a hydrogen bond and hydrophobic interactions. ConclusionCurcumolide has anti-angiogenic activity in HUVECs and in a murine OIR model of ischemia-induced retinal neovascularization, and it might be a potential drug candidate for the treatment of proliferative diabetic retinopathy.

Reading deficits in diabetic patients treated with panretinal photocoagulation and good visual acuity.

Patients with proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) can have abnormal visual functioning that may be missed by Snellen visual acuity alone. We investigated reading deficits in patients treated with PRP for PDR using the Minnesota reading (MNREAD) test. Thirty patients treated with PRP and 15 controls underwent best-corrected visual acuity (BCVA), the MNREAD, frequency doubling perimetry (FDP), and fundus photography. Panretinal photocoagulation (PRP)-treated subjects were compared to controls on MNREAD results by two-sample t-tests and Wilcoxon tests and Pearson correlations were used to assess the association between performance on MNREAD and other central visual function tests within PRP subjects. Panretinal photocoagulation (PRP)-treated patients had reduced MNREAD acuity (p<0.0001) and increased critical print size (p=0.01) compared to controls but not a significantly reduced maximum reading speed (p=0.06). Logmar MNREAD acuity was strongly positive correlated with logMAR BCVA (r=0.58, p=0.0098) and strongly negatively correlated with FDP foveal threshold (r=-0.63, p=0.0030). Maximum reading speed was positively correlated with FDP foveal threshold (r=0.57, p=0.0143) and FDP mean deviation (r=0.51, p=0.0432). Visual acuity did not correlate with the sensitivities on the FDP. The MNREAD test reveals that PRP reduces reading ability and other aspects of macular function, and thus provides new understanding of how vision-related quality of life is impaired. These findings may lead to improved means to evaluate and enhance vision following treatment for PDR.

Анализ результатов собственного опыта лечения пролиферативной диабетической ретинопатии

Анализ результатов собственного опыта лечения пролиферативной диабетической ретинопатии

Current and Future Pharmacologic Therapies for Diabetic Retinopathy.

Currently, diabetic retinopathy is the leading cause of permanent visual loss in workingage adults in industrialized nations. The chronic microangiopathic changes associated with diabetic retinopathy lead to the most common causes of severe permanent visual loss: diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Multiple studies have evaluated different pharmacotherapies for different levels of retinopathy. A review of the pathophysiology of diabetic retinopathy and current and emerging pharmacotherapies for diabetic retinopathy. Historically, DME has been the primary focus of treatment in patients with nonproliferative diabetic retinopathy (NPDR). Due to the rapidly increasing number of agents and treatment options, management algorithms for DME have become increasingly complex. Furthermore, spectral domain optical coherence tomography (OCT) has allowed unparalleled sensitivity and specificity for detecting macular edema. All available intravitreal vascular endothelial growth factor (VEGF) inhibitors have demonstrated efficacy in the treatment of patients with DME and PDR. Intravitreal triamcinolone acetonide has also proven beneficial in diabetic retinopathy. Most recently, various corticosteroids have been designed as sustained-release intraocular implants in order to reduce the burden and risks associated with retreatment. Current research is focused on providing new agents that target alternate pathways and signaling molecules to provide patients with additional therapeutic tools, especially in patients who have an incomplete response to the current medications. Anti-VEGF therapy has revolutionized the medical management of diabetic retinopathy. The most important existing challenges in the treatment of diabetic retinopathy are improving visual outcomes and decreasing the treatment burden associated with repeated intravitreal injections. Combination therapy with anti-VEGF and corticosteroids with other previously available treatments, such as panretinal photocoagulation, may be a reasonable clinical strategy to reduce the intravitreal injections burden. Many exciting novel drugs that target newly discovered pathways hold clinical promise. The results of ongoing randomized clinical trials will answer the important concerns surrounding new drugs and delivery devices: safety and visual outcomes.