Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

AIM: To assess the effects of intravitreal ranibizumab(IVR) on angiogenesis and glial activity of the fibrovascular membrane(FVM) in patients with proliferative diabetic retinopathy(PDR). METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group(n=16) did not receive IVR, while IVR group(n=26) underwent IVR 5 d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin(H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density(MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein(GFAP) and α-smooth muscle actin(α-SMA) as markers of glialmesenchymal transition(GMT). The GMT index(GI;ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs. RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups(P>0.05). The MVD of the IVR group(130.62±15.46/mm~2) was significantly lower than that of the controls(142.25±19.16/mm~2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson’s correlation coefficients(PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls(P<0.05). GI in the IVR group(1.10±0.10) was significantly lower than in the controls(1.21±0.12, P<0.05). CONCLUSION: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR.

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

AIM: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.METHODS: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.RESULTS: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 bestcorrected 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.CONCLUSION: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.