Proliferative Diabetic Retinopathy Eyes Research Articles

Vitrectomy for vitreous haemorrhage due to proliferative diabetic retinopathy in eyes with mild visual impairment.

Vitrectomy for vitreous haemorrhage due to proliferative diabetic retinopathy in eyes with mild visual impairment.

Anterior Chamber Flare as a Non-Invasive Assessment of Intraocular Immune Status and Ocular Complications in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman's rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy.

To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Referrals for proliferative diabetic retinopathy from two UK diabetic retinopathy screening services: a 10-year analysis of visual outcomes, requirement for vitrectomy, and mortality

Background/objectivesTo determine long-term outcomes of patients referred with proliferative diabetic retinopathy (PDR) from diabetic eye screening programmes (DESP) to tertiary care centres in the United Kingdom (UK).MethodsRetrospective multicentre study of patients referred from two DESPs in the UK over a 36-month period (2007–9) and followed-up for 10 years. Critical outcomes included severe vision loss (SVL) and the need for vitrectomy. Other outcomes assessed included moderate vision loss (MVL), and patient survival time. Univariate and multiple variable Cox proportional hazards regressions were used to analyse survival outcomes.Results212 eyes of 150 patients were referred with a diagnosis of PDR. 109 eyes of 72 patients were confirmed to have active PDR and included in the study. 61% of patients had low-risk PDR, while 39% exhibited high-risk features in at least one eye. Eight (7.3%) eyes developed SVL and 16 (14.7%) MVL during follow up. Vitrectomy was required in 24% (95% CI: 15 to 31%) of all PDR eyes and was most commonly performed for vitreous haemorrhage (65%). The 10-year survival in all PDR patients was 76% (95% CI: 63 to 85%) with the mean time to death for all deceased patients being 5.4 ± 3.6 years.On multivariable analysis, only age was found to have a significant association with the survival of patients with PDR.ConclusionsDuring the 10 year follow up SVL was uncommon, but MVL occurred in almost one-fifth of the eyes. Approximately 1 in 4 eyes required vitrectomy, highlighting its significance in patient management.

Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept

PurposeTo compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. MethodsThis study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. ResultsDuring a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). ConclusionThe aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

Optical Coherence Tomography Angiography of Volumetric Arteriovenous Relationships in the Healthy Macula and Their Derangement in Disease.

To characterize relative arteriovenous connectivity of the healthy macula imaged by optical coherence tomography angiography (OCTA) using a new volumetric tool. OCTA volumes were obtained for 20 healthy controls (20 eyes). Two graders identified superficial arterioles and venules. We implemented a custom watershed algorithm to identify capillaries most closely connected to arterioles and venules by using the large vessels as seeds to flood the vascular network. We calculated ratios of arteriolar- to venular-connected capillaries (A/V ratios) and adjusted flow indices (AFIs) for superficial capillary plexuses (SCPs), middle capillary plexuses (MCPs), and deep capillary plexuses (DCPs). We also analyzed two eyes with proliferative diabetic retinopathy (PDR) and one eye with macular telangiectasia (MacTel) to evaluate the utility of this method in visualizing pathological vascular connectivity. In healthy eyes, the MCP showed a greater proportion of arteriolar-connected vessels than the SCP and DCP (all P < 0.001). In the SCP, the arteriolar-connected AFI exceeded the venular-connected AFI, but this pattern reversed in the MCP and DCP, with higher venular-connected AFI (all P < 0.001). In PDR eyes, preretinal neovascularization originated from venules, whereas intraretinal microvascular abnormalities were heterogeneous, with some originating from venules and others representing dilated MCP capillary loops. In MacTel, diving SCP venules formed the epicenter of the outer retinal anomalous vascular network. Healthy eyes showed a higher MCP A/V ratio but relatively slower arteriolar vs. venular flow velocity in the MCP and DCP, which may explain deep retinal vulnerability to ischemia. In eyes with complex vascular pathology, our connectivity findings were consistent with histopathologic studies.

Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema

To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p < 0.001). The morphology of MLCs in DME eyes appeared larger and fuller. NPDR eyes had higher number and density of MLCs (p = 0.027 and 0.026), greater central macular thickness (CMT) (p = 0.002) and vessel density than PDR eyes in non-DME group but comparable to PDR eyes in DME group. The number and density of MLCs at macular region were significantly higher with larger and fuller morphology in DR patients with DME than those without DME. PDR eyes had fewer MLCs than NPDR eyes for DR eyes without DME.

Association between Systemic Factors and Vitreous Fluid Cytokines in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Systemic and intraocular factors are intricately related to PDR, and vitreous fluid (VF) cytokines are representative intraocular biomarkers. However, the associations between systemic factors and VF cytokines and their influence on PDR pathology are unclear. This study aimed to examine the correlation between systemic factors and VF cytokines and analyze their contributions to the pathology of PDR using multivariate analyses. We conducted a retrospective observational study on 26 PDR eyes of 25 patients with type 2 DM, and 30 eyes of 30 patients with idiopathic macular hole or epiretinal membrane as controls. Fifteen systemic and laboratory tests including blood pressure (BP) and body mass index (BMI), and 27 cytokines in VF were analyzed. BP and BMI correlated positively with VF levels of IL-6 and IP-10 in PDR patients, while no significant correlation was found between systemic factors and VF cytokines in controls. MCP-1 and VEGF-A in VF separately clustered with different systemic factors in controls, but these cytokines lost the property similarity with systemic factors and acquired property similarity with each other in PDR. Systemic factors contributed to only 10.4%, whereas VF cytokines contributed to 42.3% out of 52.7% variance of the whole PDR dataset. Our results suggest that intraocular factors play a major role in the pathology of PDR, whereas systemic factors may have limited effects, and that BP and BMI control in PDR could be useful interventions to improve intraocular immune condition.

Characteristics of Unexposed Proliferative Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study

Purpose: To compare optical coherence tomography angiography (OCTA) findings between severe non-proliferative diabetic retinopathy (NPDR) and unexposed proliferative diabetic retinopathy (PDR), and identify predictive factors.Methods: Patients newly diagnosed with severe NPDR or unexposed PDR between January 2018 and December 2021 were reviewed retrospectively. Unexposed PDR was diagnosed using fluorescein fundus angiography, because new vessels could not be observed in the poster pole or clearly distinguished in the retinal periphery on wide fundus photography. Clinical features at the time of diagnosis, and OCTA measurements (mean vascular density, superficial capillary plexus (SCP) foveal avascular zone (FAZ) area, and mean retinal thickness), were compared between the two groups. Factors that could predict unexposed PDR were investigated using multivariate analysis with a generalized estimating equation.Results: A total of 61 severe NPDR and 23 unexposed PDR eyes were included. The unexposed PDR had significantly larger SCP-FAZ areas (&lt;i&gt;p&lt;/i&gt; = 0.031) and lower total and parafoveal mean inner retinal thicknesses (&lt;i&gt;p&lt;/i&gt; = 0.014 and &lt;i&gt;p&lt;/i&gt; &lt; 0.001, respectively). However, there were no differences in mean vascular density between the groups (&lt;i&gt;p&lt;/i&gt; &gt; 0.05). Multivariate analysis showed that SCP-FAZ area and parafoveal mean inner retinal thickness were significant predictors of unexposed PDR (&lt;i&gt;p&lt;/i&gt; = 0.027 and &lt;i&gt;p&lt;/i&gt; = 0.001, respectively).Conclusions: In severe NPDR patients, unexposed PDR may be considered a differential diagnosis when the SCP-FAZ area is large or the parafoveal mean inner retinal thickness is small.

Proliferative diabetic retinopathy and diabetic macular edema are two factors that increase macrophage-like cell density characterized by en face optical coherence tomography

BackgroundMacrophage-like cells (MLCs) located at the ILM were observed in live human retinas using adaptive optics optical coherence tomography (OCT) as well as clinically-used OCT. The study aimed to quantitatively analyzing MLCs at the vitreoretinal interface (VRI) in diabetic retinopathy (DR) using en face OCT and swept-source optical coherence tomography angiography (SS-OCTA).Methods190 DR eyes were included in the study, with 70 proliferative diabetic retinopathy (PDR) eyes and 120 non- proliferative diabetic retinopathy (NPDR) eyes. Sixty-three eyes from normal subjects were included as controls. MLCs were visualized in a 5 μm en face OCT slab above the VRI centered on the fovea. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the OCTA parameters and the MLC parameters among groups. We evaluated the MLC density among groups on binarized images after image processing. We also investigated the relationship between MLC density and other OCT parameters including retina thickness and vessel density (VD).ResultsThe MLC density significantly increased in PDR eyes (PDR vs. NPDR, 8.97 (8.40) cells/mm2 vs.6.14 (8.78) cells/mm2, P = 0.013; PDR vs. normal, 8.97 (8.40) cells/mm2vs. 6.48 (6.71) cells/mm2, P = 0.027) and diabetic macular edema (DME) eyes (DME vs. without DME, 8.94 (8.26) vs.6.09 (9.00), P = 0.005). After adjusting for age and gender, MLC density in NPDR eyes negatively correlated to VD of deep capillary plexus (DCP) (P = 0.01).ConclusionsSS-OCTA is a non-invasive and simple method for the characterization of MLCs at the VRI. PDR and DME are two factors that increase MLC density. MLC density also correlated with VD.

Post-vitrectomy delayed retinal breaks in proliferative diabetic retinopathy

PurposeTo report a series of cases of post-operative new secondary retinal breaks following vitrectomy for proliferative diabetic retinopathy (PDR).MethodsThis retrospective case series included data of patients diagnosed with post-operative retinal breaks following uneventful vitrectomy surgery for PDR from January 2018 to December 2021.ResultsNew post-vitrectomy retinal breaks in PDR were seen in 7% of eyes (n = 10/148 eyes; 10 patients). Age of study patients ranged from 45 to 69 years and there were 8 males. Vitreous surgery was performed for vitreous hemorrhage in six eyes, macular tractional retinal detachment in three eyes and epiretinal membrane in one eye. Tractional fibrovascular proliferation near the retinal break prior to its development was noted either pre- or intra-operatively in 8 eyes. Mean time interval between the vitreous surgery and secondary retinal break development was 6.4 months. Residual fibrous tissue post-surgery adjacent to the break was noted in 4 cases. Sclerosed retinal vessel was noted in 4 eyes and associated inner retinal thinning or schisis in 5 eyes. No retinal detachment was noted in any case. Prophylactic barrage was done in 4 eyes. Last follow-up interval ranged from 4 to 53 months and visual acuity ranged from 6/6 to 6/60. No subretinal fluid, traction or break enlargement was noted at the last visit.ConclusionDelayed post-operative retinal breaks following vitrectomy are uncommon in PDR eyes. Careful preoperative evaluation of the retinal proliferations, intraoperative dissection of the membranes and regular post-operative reviews are vital in anticipating the development of delayed post-vitrectomy retinal breaks. Observation could be the management strategy for these breaks.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6mm and Montage 15 × 15mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.

Clinical Features Distinguishing Diabetic Retinopathy Severity Using Artificial Intelligence

Background and Hypothesis:1 in 29 American diabetics suffer from diabetic retinopathy (DR), the weakening of blood vessels in the retina. DR goes undetected in nearly 50% of diabetics, allowing DR to steal the vision of many Americans. We hypothesize that increasing the rate and ease of diagnosing DR by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients.&#x0D; Project Methods:This retrospective cohort study was conducted under approval from the Institutional Review Board of Indiana University School of Medicine. Images were deidentified and no consent was taken due to the nature of this retrospective study. We categorized 676 patient files based upon HbA1c, severity of non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Retinal images were annotated to identify common features of DR: microaneurysms, hemorrhages, cotton wool spots, exudates, and neovascularization. The VGG Image Annotator application used for annotations allowed us to save structure coordinates into a separate database for future training of the artificial intelligence system.&#x0D; Results:228 (33.7%) of patients were diagnosed with diabetes, and 143 (62.7%) of those were diagnosed with DR. Two-sample t tests found significant differences between the HbA1c values of all diabetics compared to diabetics without retinopathy (p&lt;0.007) and between all severities of DR versus diabetics without retinopathy (p&lt;0.002). 283 eyes were diagnosed with a form of DR in this study: 37 mild NPDR, 42 moderate NPDR, 56 severe NPDR, and 148 PDR eyes.&#x0D; Potential Impact:With the dataset of coordinates and HbA1c values from this experiment, we aim to train an artificial intelligence system to diagnose DR through retinal imaging. The goal of this system is to be conveniently used in primary medical clinics to increase the detection rate of DR to preserve the ocular health of millions of future Americans.

Comparison of Chorioretinal Parameters in Diabetic Retinopathy with or without Pan-Retinal Photocoagulation Using Ultrawide-Field Swept-Source Optical Coherence Tomography Angiography

Introduction: To compare structural and vascular parameters in the central and peripheral retina and choroid of eyes diagnosed with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) with or without pan-retinal photocoagulation (PRP) using ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA). Methods: All participants underwent SS-OCTA imaging centered on the fovea. Retinal and choroidal thickness, vessel density of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary plexus (CCP), and choroidal Sattler’s and Haller’s layer (CSHL) were analyzed in nine grids using built-in angiography analysis software. Results: A total of 82 eyes from 82 participants were enrolled in this study, including 40 eyes diagnosed with severe NPDR or PDR without PRP and 42 eyes with PRP. Retinal thickness in part grids was higher in eyes with PRP than in eyes without PRP. Vessel density of the SCP in nasal-superior (p = 0.003) grid was lower in eyes with PRP than in eyes without PRP. No significant difference was found in the vessel density of the DCP between the two groups (all p > 0.05). The choroidal thickness and vessel density of the CSHL of all grids were significantly lower in eyes with PRP than in eyes without PRP (all p < 0.05). A statistically significant decrease in vessel density in CCP was found in the superior (p = 0.043), nasal-superior grid (p = 0.003), macular grid (p < 0.001), and optic disc grid (p = 0.001) of eyes with PRP, compared to eyes without PRP. A significant decrease in the vessel density of CSHL was observed in all grids of PDR eyes with PRP compared to PDR eyes without PRP (all p < 0.05). Significant decrease in choroidal thickness was observed in most grids of PDR eyes with PRP, except for macular grid (p = 0.090) and optic disc grid (p = 0.057). Conclusion: Structural and vascular parameters in the central and peripheral retinal and choroidal layers in eyes diagnosed with severe NPDR or PDR with or without PRP could be quantified using a ultrawide-field SS-OCTA. Eyes with PRP showed a significant decrease in choroidal thickness and vessel density of CCP and CSHL, compared with eyes without PRP. This trend was more obvious in eyes with PDR.

Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients.

To analyze concentrations of vascular endothelial growth factor (VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy (PDR) patients pre-treated with intravitreal anti-VEGF injections (IVI) at different time periods prior to pars plana vitrectomy (PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI. The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDR-related complications (PDR group) and 21 eyes with non-diabetic ocular disease (control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3d after IVI (3-day group); 5d after IVI (5-day group); 7 or more days after IVI (≥7-day group); and no IVI. Vitreous fluid samples (0.5-1.0 mL) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor (bFGF), periostin (PN), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis. PDR eyes without IVI had significantly higher VEGF, bFGF, PN, and IL-6 concentrations than non-diabetic eyes (all P<0.05), and had a significantly higher concentration of VEGF (P<0.05) and a significantly lower concentration of IL-8 (P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, bFGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups (all P<0.05); meanwhile there was no significant difference in TNF-α among groups (P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of bFGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day (P=0.015) and 5-day group (P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of bFGF, PN, IL-6, and IL-8 (all P<0.05). Univariate ordinal logistic regression analysis showed that bFGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI. The vitreous concentrations of VEGF, bFGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angio-fibrosis switch. The results suggest that PPV should be performed 5d after IVI administration in PDR patients.

Prognosis value of Chinese Ocular Fundus Diseases Society classification for proliferative diabetic retinopathy on postoperative visual acuity after pars plana vitrectomy in type 2 diabetes.

To compare the postoperative visual acuity among eyes with proliferative diabetic retinopathy (PDR) of different stages after pars plana vitrectomy (PPV) in type 2 diabetic patients. A retrospective study was conducted for PDR eyes undergoing PPV in type 2 diabetic patients. All patients were divided into three groups based on Chinese Ocular Fundus Diseases Society (COFDS) classification for PDR: Group A (primary vitreous hemorrhage), Group B (primary fibrovascular proliferation) and Group C (primary vitreous hemorrhage and/or fibrovascular proliferative combined with retinal detachment). The postoperative visual acuity and the change between postoperative and preoperative visual acuity were compared among three groups. The associated risk factors for postoperative visual acuity were analyzed in the univariate and multiple linear aggression. In total, 195 eyes of 195 patients were collected in this study, including 71 eyes of 71 patients in Group A, 75 eyes of 75 patients in Group B and 49 eyes of 49 patients in Group C. The eyes in Group A got better postoperative best-corrected visual acuity (BCVA) compared to the eyes in Group B and C (0.48±0.48 vs 0.89±0.63, P<0.001; 0.48±0.48 vs 1.04±0.67, P<0.001; respectively). The eyes in Group A got more improvement of BCVA compared to the eyes in Group B and C (1.07±0.70 vs 0.73±0.68, P=0.004; 1.07±0.70 vs 0.77±0.78, P=0.024; respectively). In the multiple linear regression analysis, primary fibro-proliferative type (β=0.194, 95%CI=0.060-0.447, P=0.01), retinal detachment type (β=0.244, 95%CI=0.132-0.579, P=0.02), baseline logMAR BCVA (β=0.192, 95%CI=0.068-0.345, P=0.004), silicone oil tamponade (β=0.272, 95%CI=0.173-0.528, P<0.001) was positively correlated with postoperative logMAR BCVA. Eyes undergoing phacovitrectomy had better postoperative BCVA (β=-0.144, 95%CI=-0.389 to -0.027, P=0.025). PDR eyes of primary vitreous hemorrhage type usually have better visual acuity prognosis compared to primary fibrovascular proliferation type and retinal detachment type. COFDS classification for PDR may have a high prognostic value for postoperative visual outcome and surgical management indications.

Impact of Intravitreal Anti-VEGF Therapy on Microperimetry of the Retinal Nonperfusion Areas of Patients with Proliferative Diabetic Retinopathy.

This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WFOCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas. This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WFOCTA and MP-1 at baseline (T0) and 1month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)]. Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD. An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response.

Peripapillary circulatory dysfunction precedes structural loss in treatment-naive diabetic retinopathy.

The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR). One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas. RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters. Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR.

Inflammatory cytokines and retinal nonperfusion area in quiescent proliferative diabetic retinopathy.

We sought to investigate the association between inflammatory cytokine levels and retinal capillary nonperfusion area in eyes with quiescent proliferative diabetic retinopathy (PDR). Samples of aqueous humor were collected from 67 eyes (n = 42 patients) with treatment-naïve PDR. Levels of interleukin (IL)-10, IL-1β, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor-α (TNF-α) were obtained using multiplex bead assay. Areas of capillary nonperfusion at the posterior pole and peripheral retina were measured via ultra-widefield fluorescein angiography and correlated with cytokine levels. The levels of IL-10, IL-6, IL-8, MCP-1, and TNF-α were positively correlated with the nonperfusion area of the peripheral retina (r = 0.298, 0.401, 0.265, 0.435, and 0.393; all P ≤ 0.030). There were positive correlations between IL and 10, IL-6, IL-8, MCP-1, and TNF-α (all R ≥ 0.247; all P ≤ 0.043). IL-1β did not show a significant correlation with the nonperfusion area (P = 0.972 for posterior pole and 0.392 for periphery) but was positively correlated with TNF-α (r = 0.334; P = 0.006). An increased level of inflammation was observed in PDR eyes with larger nonperfusion areas, which suggests inflammation as a possible target for suppressing PDR progression associated with nonperfusion.

Correlation of Complement Activation in Aqueous and Vitreous in Patients With Proliferative Diabetic Retinopathy.

PurposeA growing body of evidence suggests complement dysregulation is present in the vitreous of patients with diabetic eye disease. Further translational study could be simplified if aqueous—as opposed to vitreous—were used to sample the intraocular complement environment. Here, we analyze aqueous samples and assess whether a correlation exists between aqueous and vitreous complement levels.MethodsWe collected aqueous, vitreous, and plasma samples from patients with and without proliferative diabetic retinopathy (PDR) undergoing vitrectomy. We assessed correlation between complement levels in aqueous and vitreous samples after using a normalizing ratio to correct for vascular leakage. Spearman correlation coefficients were used to assess the correlation between complement levels in the aqueous and vitreous.ResultsAqueous samples were obtained from 17 cases with PDR and 28 controls. In all patients, aqueous Ba, C3a, and albumin levels were strongly correlated with vitreous levels (Spearman correlation coefficient of 0.8 for Ba and C3a and 0.7 for albumin; all P values < 0.0001). In PDR eyes only, aqueous and vitreous C3a levels were significantly correlated (Spearman correlation coefficient 0.7; P = 0.002), whereas in control eyes, both Ba and C3a (Spearman correlation coefficients of 0.7; P < 0.0001) were significantly correlated.ConclusionsA strong correlation exists between aqueous and vitreous complement levels in diabetic eye disease.Translational RelevanceThe results establish that accurate sampling of the intraocular complement can be done by analyzing aqueous specimens, allowing for the rapid and safe measurement of experimental complement targets and treatment response.