Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Effects of a fortified balanced salt solution and Ringer's lactate solution on anterior chamber inflammation after phacoemulsification in diabetes.

PURPOSE: To compare the effects of a fortified balanced salt solution (fSS) and Ringer's lactate solution (Ringer) on anterior chamber (AC) inflammation in patients undergoing phacoemulsification. SETTING: Tianjin Medical University Eye Hospital, Tianjin, China. DESIGN: Prospective masked controlled trial. METHODS: 80 patients (40 patients with regular cataract and 40 cataract patients with diabetes mellitus [DM]) were randomized to receive either fSS (n = 40) or Ringer's solution (n = 40). Anterior-segment optical coherence tomography was used to evaluate AC cells and flare. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence were used for tight junction examination. Monocytic leukemia cell line (Tohoku Hospital Pediatrics-1 [THP-1]) transmigration assay was performed to observe the effects of the 2 perfusates on the inflammatory response in vitro. RESULTS: In patients with regular cataracts, postoperative AC cells and flare on the 1st and 7th days were not significantly different between the Ringer and fSS groups. However, in cataract patients with DM, AC cells were higher in the Ringer group than in the fSS group ( P = .003) on postoperative day 1. The AC flare was also significantly higher in the Ringer group than in the fSS group ( P < .0001). No significant differences between the groups were observed on day 7. Compared with Ringer, fSS increased the TEER value and ZO-1 content and reduced the adhesion of THP-1 cells. CONCLUSIONS: The results of this study indicated that early postoperative AC inflammation is more severe in patients with cataracts and DM. In addition, fSS attenuates inflammation by protecting the blood-aqueous barrier and inhibiting the exudation of inflammatory cells.

Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.

PURPOSE: To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). METHODS: A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. RESULTS: Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. CONCLUSIONS: Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. TRIAL REGISTRATION: The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.

Study on the effects of different anti-VEGF drugs on fibrovascular membranes of proliferative diabetic retinopathy.

PURPOSE: To investigate the effects of different anti-VEGF drugs on fibrovascular membranes (FVM) in proliferative diabetic retinopathy (PDR). In addition, in vitro model was used to simulate the intraocular fibroblasts barrier to explore the penetration of different anti-VEGF drugs. METHODS: 24 eyes from 24 PDR patients with FVM were recruited for this prospective observational study. The patients were randomized to receive one of three anti-VEGF drugs (Ranibizumab, Conbercept, or Aflibercept). Then neovascular structures were assessed by optical coherence tomography angiography (OCTA) before intravitreal injection (pre-IVT) and 1, 2, and 3 days after intravitreal injection (post-IVT). The changes in vessels area (VSA), vessels percentage area (VPA), junction density (JD), and average lacunarity (AL) were analyzed by using the image processing software Angiotool. In vitro penetrating model with fibroblasts barrier was used to compare the effects of the three drugs on human retinal vascular endothelial cells (HRVECs) over 3 days by Cell proliferation measurement. Moreover, the drug concentrations in the penetrating model were detected by liquid chromatography-mass spectrometry (LC-MS). RESULTS: The VSA, VPA, and JD all decreased, while the AL increased in Ranibizumab group(n = 8), Conbercept group (n = 8), and Aflibercept group (n = 8) within 3 days (P<0.05). Meanwhile, under the condition of the same amount of substance, the inhibition effect of Ranibizumab on HRVEC was the strongest in the penetrating model evaluated by CCK8 absorbance experiments of HRVECs (FCCK8=6.493, PCCK8= 0.0051), and the number of transmembrane molecules in the Ranibizumab group was also the largest within 3 days (F = 8.209, P = 0.0006) among the three groups. CONCLUSION: Angiotool is feasible to reconstruct the neovascular structure on the FVM in OCTA images. The three different anti-VEGF drugs can significantly reduce the vascular area and density on the proliferating membranes, and there is no significant difference in the anti-neovascularization among the three drugs clinically. However, small molecule drug is more penetrating and move faster across membranes in vitro cell model. CLINICAL TRIAL REGISTRATION: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2300067476).

Evaluating the effect of vitreomacular interface abnormalities on anti-vascular endothelial growth factor treatment outcomes in diabetic macular edema by optical coherence tomography: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of vitreomacular interface (VMI) configuration on treatment outcomes after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) using optical coherence tomography (OCT). METHODS: A systematic literature search was performed on PubMed, Embase, web of science and clinicaltrials.gov. The primary outcome parameters were central macular thickness (CMT), best-corrected visual acuity (BCVA) and mean injection numbers. We performed this meta-analysis by Review Manager (RevMan) 5.4.1. RESULTS: The impact of epiretinal membrane (ERM), vitreomacular traction (VMT) and vitreomacular adhesion (VMA) on the treatment outcomes were analyzed separately. 9 clinical studies involving 699 eyes were eligible for the meta-analysis for evaluating the effect of ERM/VMT on efficacy. And 7 studies with 610 eyes were included to access whether VMA affected the response to anti-VEGF therapy in patients with DME. The ERM/VMT group had poorer CMT reductions than the control group at 1 month ([MD] 52.91 mm, P<0.00001), while no significant difference at 3 months ([MD] 43.95 mm, P = 0.22) and over 12 months ([MD] 30.51 mm, P = 0.45). No statistically significant difference in the mean BCVA change at 1 month ([MD] -0.03 Log MAR, P = 0.79), whereas ERM/VMT group had poor visual acuity gains at 3 months ([MD] 0.08 Log MAR, P = 0.003), and a tendency of poor vision improvement over 12 months follow-up ([MD] 0.07 Log MAR, P = 0.11). There was no significant difference in the visual and anatomical results over 3 months in DME patients with or without VMA ([MD] -21.92 mm, P = 0.09; [MD] 1.79 letters, P = 0.22). Besides, VMI configuration was not found to affect mean injection numbers. CONCLUSION: The limited evidence suggested that ERM/VMT was associated with worse CMT reduction at 1 month, poor BCVA gain at 3 months and a tendency of limited vision improvement over 12 months follow-up in DME patients treated with anti-VEGF agents. And VMA may not adversely affect the anatomic and functional outcomes. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among study designs.

Association of metformin treatment with enhanced effect of anti-VEGF agents in diabetic macular edema patients.

PURPOSE: To investigate the effect of metformin combined with anti-VEGF agents in patients with diabetic macular edema (DME). METHODS: This study was a prospective, nonrandomized case-control study. Patients were included in with a diagnosis of DME who received anti-VEGF agents injection. Basic information, medical history, best-corrected visual acuity (BCVA), central macular thickness (CMT), the number of intravitreal injections, panretinal photocoagulation (PRP), and macular grid photocoagulation treatment during the 6-month follow-up, were recorded for each patient. RESULTS: A total of 50 DME patients were collected (24 patients with a history of oral metformin ≥ 6 months and 26 patients who had not taken metformin). The BCVA and the CMT were significantly improved after anti-VEGF treatment in two groups (F1 = 19.35, F2 = 26.78; F1 = 65.45, F2 = 76.23; P < 0.05). The BCVA in the metformin group was better than that in non-metformin group at every point after treatment (F = 34.45, P < 0.05). The CMT in metformin group decreased much more than that in non-metformin group during the follow-up period (F = 87.05, P < 0.05). The injection numbers decreased in the metformin group compared with the non-metformin group (t = 5.14, P < 0.05). However, there was no difference in PRP and macular grid photocoagulation therapy between the two groups during the 6-month follow-up. CONCLUSION: Metformin can enhance the therapeutic effect of anti-VEGF agents on DME patients to improve their visual acuity, improve the structure of the macular area, and reduce the number of intravitreal injections 90.