Interleukin (IL)-6, interleukin (IL)-8 levels and cellular composition of the vitreous humor in proliferative diabetic retinopathy, proliferative vitreoretinopathy, and traumatic proliferative vitreoretinopathy

PURPOSE: To investigate the interleukin (IL)-6 levels, IL-8 levels, and cellular composition of the vitreous humor in patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and traumatic PVR. METHODS: Vitreous samples from 14 patients with PDR, 10 patients with PVR, and 10 patients with traumatic PVR were analyzed. Fifteen cadaver eyes were used as controls. Cytokine levels were measured by ELISA. RESULTS: Elevated IL-6 levels were detected in the vitreous of 12 (85.7%) of the PDR patients, eight (80%) of the PVR patients, and all (100%) of the traumatic PVR patients. None of the control IL-6 results were elevated. Vitreous IL-8 levels were elevated in 12 (85.7%) of the PDR patients, six (60%) of the PVR patients, all (100%) of the traumatic PVR patients, and one (6.7%) of the control eyes. Cytological examination of the vitreous specimens revealed a predominance of macrophages (50%) in the PDR samples and a predominance of retinal pigment epithelial (RPE) cells (60%) in the PVR samples. In contrast, neutrophils predominated (88%) in the traumatic PVR samples. CONCLUSION: The findings suggest that IL-6 and IL-8 may be involved in the pathogenesis of PDR, PVR, and traumatic PVR. High proportions of RPE cells and macrophages are associated with elevated IL-6 and IL-8 levels in the vitreous of PDR and PVR patients; however, the fact that these cells are not predominant in traumatic PVR suggests that different immune response mechanisms may be active in the pathogenesis of these disorders.     

Interleukin (IL)-6, Interleukin (IL)-8 Levels and Cellular Composition of the Vitreous Humor in Proliferative Diabetic Retinopathy,Proliferative Vitreoretinopathy,and Traumatic Proliferative Vitreoretinopathy

Purpose: To investigate the interleukin (IL)-6 levels, IL-8 levels, and cellular composition of the vitreous humor in patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and traumatic PVR. Methods: Vitreous samples from 14 patients with PDR, 10 patients with PVR, and 10 patients with traumatic PVR were analyzed. Fifteen cadaver eyes were used as controls. Cytokine levels were measured by ELISA. Results: Elevated IL-6 levels were detected in the vitreous of 12 (85.7%) of the PDR patients, eight (80%) of the PVR patients, and all (100%) of the traumatic PVR patients. None of the control IL-6 results were elevated. Vitreous IL-8 levels were elevated in 12 (85.7%) of the PDR patients, six (60%) of the PVR patients, all (100%) of the traumatic PVR patients, and one (6.7%) of the control eyes. Cytological examination of the vitreous specimens revealed a predominance of macrophages (50%) in the PDR samples and a predominance of retinal pigment epithelial (RPE) cells (60%) in the PVR samples. In contrast, neutrophils predominated (88%) in the traumatic PVR samples. Conclusion: The findings suggest that IL-6 and IL-8 may be involved in the pathogenesis of PDR, PVR, and traumatic PVR. High proportions of RPE cells and macrophages are associated with elevated IL-6 and IL-8 levels in the vitreous of PDR and PVR patients; however, the fact that these cells are not predominant in traumatic PVR suggests that different immune response mechanisms may be active in the pathogenesis of these disorders.     

Upregulation of RAGE and its ligands in proliferative retinal disease

We sought to study the presence of the receptor for advanced glycation endproducts (RAGE) and its ligands, advanced glycation endproducts (AGEs), S100/calgranulins and amphoterin (high mobility group box 1 protein; HMGB1), in the vitreous cavity and epiretinal membranes (ERMs) of eyes of patients with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Undiluted vitreous specimens were collected from 30 eyes of 30 patients undergoing pars plana vitrectomy for repair of retinal detachment (RD) secondary to PDR (n = 15) or PVR (n = 15). The vitreous samples obtained from 10 eyes undergoing macular hole repair were used as controls. Epiretinal membranes were obtained from eight eyes with PDR and from 10 eyes with PVR. The levels of AGEs in the vitreous were measured using ELISA. The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. The vitreous levels of sRAGE were significantly increased in both PDR and PVR (p < or = 0.05) compared to control vitreous. In both PDR and PVR, the vitreous levels of AGEs (p < or = 0.01), S100/calgranulins (p < or = 0.05), and amphoterin (p < or = 0.01) were also elevated compared to control eyes. Expression of RAGE was detected in six of eight ERMs from eyes with PDR and eight of 10 ERMs from eyes with PVR. Many cells expressing RAGE also expressed vimentin, suggesting a glial cell origin. Ligands for RAGE were also detected in ERMs, with AGEs detected in five eyes with PDR and eight eyes with PVR. Similarly, S100 and amphoterin ERM expression was observed in six eyes with PDR; these ligands were also expressed in ERMs from eyes with PVR (8 and 7 cases, respectively). We conclude that RAGE and its ligands are increased in the vitreous cavity of eyes with PDR and PVR and are present in ERMs of eyes with these proliferative retinal disorders. These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases.     

增生性玻璃体视网膜疾病眼内液血管内皮生长因子的表达

目的 观察增生性玻璃体视网膜疾病患者眼内液（房水、玻璃体）中血管内皮生长因子（VEGF）含量的变化规律，探讨VEGF在增生性玻璃体视网膜疾病发展变化中的作用。 方法 采用双抗体夹心酶联免疫吸附试验(ELISA)定量检测增生性玻璃体视网膜病变（PVR）、视网膜静脉阻塞（RVO）、增生性糖尿病视网膜病变（PDR）、新生血管性青光眼（NVG）患者组及正常对照组房水、玻璃体VEGF含量。 结果 PVR、RVO、PDR、NVG患者组房水及玻璃体VEGF含量均高于正常对照组，其差异均有统计学意义(P<0.05)；NVG、PDR、RVO、PVR患者组房水及玻璃体VEGF含量依次降低 ，其差异有统计学意义(P<0.05)；PVR、RVO、PDR、NVG患者组和正常对照组玻璃体VEGF含量均高于房水VEGF含量，其差异有统计学意义(P<0.05)；PVR患者病史与房水、玻璃体VEGF含量呈负相关（r分别为－0.819、－0.823，P＜0.05）；RVO患者病史与房水、玻璃体VEGF含量呈正相关（r分别为0.913、0.929，P＜0.05）；PDR患者玻璃体积血时间与房水、玻璃体VEGF含量呈正相关（r分别为0.905、0.920，P＜0.05）。 结论 增生性玻璃体视网膜疾病患者房水及玻璃体VEGF含量明显增高，VEGF可能在增生性玻璃体视网膜疾病发展变化中起着重要的作用。 (中华眼底病杂志， 2006， 22：313-316）     

Silicone oil in the treatment of complicated retinal detachments

Silicone oil is now used with increasing frequency to treat cases of complicated retinal detachment (RD). The authors report their results using silicone oil in eyes with RD resulting from proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). The retina was completely reattached at last examination in 16 (70%) of 23 eyes with PDR and 20 (67%) of 30 eyes with PVR. Final vision of 5/200 or better was obtained in 5 eyes with PDR (22%) and 16 eyes with PVR (53%) (P = 0.0016). Reproliferation of epiretinal membranes occurred in 26% of diabetics and 23% of eyes with PVR. Silicone oil did not cause regression of iris neovascularization. Complications of silicone oil included corneal decompensation, lens opacification, intraocular pressure elevation, and hypotony.     

Soluble cellular adhesion molecules in proliferative vitreoretinopathy and proliferative diabetic retinopathy.

PURPOSE. To measure vitreous levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cellular adhesion molecule-1 (sVCAM-1) in the eyes of patients with retinal detachment (RD) due to proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR) and to determine whether the levels of these mediators correlated with clinical parameters of disease. METHODS. Undiluted vitreous specimens were collected from 50 eyes of 48 patients undergoing vitrectomy for traction RD due to PDR (21 specimens) and recurrent RD due to PVR (19 specimens). Control vitreous specimens were obtained from patients undergoing macular hole repair (10 specimens). The levels of sICAM-1 and sVCAM-1 were measured in each sample by specific enzyme-linked immunoadsorbent assays. RESULTS. Vitreous levels of sICAM-1 were significantly increased in vitreous specimens from both PVR (median +/- SD; 12.0 +/- 76.3 ng/ml; P < 0.01) and PDR (8.4 +/- 24.0 ng/ml; P < 0.01) when compared to vitreous from eyes with macular holes (0. 3 +/- 4.2 ng/ml). Vitreous levels of sVCAM-1 were significantly increased in both PVR (36.5 +/- 255.2 ng/ml; P < 0.001) and PDR (26. 2 +/- 93.5 ng/ml; P < 0.01) when compared to control vitreous (17.7 +/- 7.8 ng/ml). The vitreous levels of sICAM-1 were higher in cases of PDR which developed recurrent proliferative disease (P < 0.01) and recurrent RD (P = 0.01), whereas the levels of sICAM-1 in PVR and sVCAM-1 in PDR and PVR did not significantly correlate with these clinical parameters. CONCLUSIONS. Soluble forms of ICAM-1 and VCAM-1 are increased in the vitreous cavity of patients with RD due to PDR or PVR, reflecting the inflammatory nature of these conditions and suggesting a possible role for these mediators in the pathogenesis of proliferative retinal disease. The vitreous levels of these sCAMs at the time of surgery may serve as a marker of inflammation, but their specific levels do not predict the likelihood of recurrent proliferation or surgical anatomic success in most cases of PVR and PDR.     

Soluble TNF receptors in vitreoretinal proliferative disease

PURPOSE: To measure vitreous levels of soluble TNF-receptors (sTNF-Rs) types I and II in eyes with rhegmatogenous retinal detachment (RRD), uncomplicated or complicated with proliferative vitreoretinopathy (PVR), and in eyes with proliferative diabetic retinopathy (PDR). To examine whether there is any relationship between vitreous levels of sTNF-Rs and clinical features of these conditions and between vitreous sTNF-Rs and TNFalpha levels and serum levels of sTNF-RS: METHODS: Vitreous levels of sTNF-Rs and TNFalpha were measured by enzyme-linked immunosorbent assay in 30 eyes with PVR, 30 eyes with uncomplicated RRD, and 29 eyes with PDR. Vitreous from eyes of 10 deceased donors and 9 eyes with macular holes served as control specimens. Serum levels of sTNF-Rs were measured in 17 patients with PDR and 21 patients with PVR. RESULTS: Vitreous levels of sTNF-Rs I and II were increased in eyes with PVR, RRD, and PDR when compared with control eyes (P < 0.002). However, vitreous levels of sTNF-Rs I and II were higher in eyes with PVR than in eyes with RRD (P < 0.01) or PDR (P < 0.03). This contrasted with the findings that serum sTNF-Rs were higher in PDR than in PVR (P < 0.016) and that vitreous levels of TNFalpha were higher in eyes with PDR than in eyes with PVR (P < 0.0005). In PVR, vitreous sTNF-Rs levels were associated with the duration of retinal detachment, number of previous external operations, and grade of severity, whereas in PDR these levels were not related to the type or duration of diabetes or its complication with traction retinal detachment. CONCLUSIONS: These observations suggest the existence of TNF inhibitory mechanisms within the eye during retinal processes of inflammation and angiogenesis. That high vitreous levels of sTNF-Rs relate to severity of retinopathy suggests that these molecules may constitute reactive products of inflammation. Effective control of TNFalpha activity by sTNF-Rs within the retinal microenvironment may determine the outcome and severity of retinal proliferative conditions.     

Cellular components of proliferative vitreoretinal membranes.

To understand the pathogenesis of proliferative vitreoretinal membrane formation which occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), etc., accurate identification of the cellular components of the membrane is needed. This study was performed to identify cellular components of the membranes by means of immunohistochemical technique. 11 proliferative vitreoretinal membranes which were surgically obtained from 7 eyes with PVR and 4 eyes with PDR were stained with monoclonal antibodies against cytokeratin, glial fibrillary acidic protein (GFAP), or vimentin using immunoperoxidase technique (ABC method). In the PVR membranes, mean cell positivities for cytokeratin, GFAP and vimentin were 48%, 1% and 92%, respectively and in the PDR membranes, 0%, 5% and 93%, respectively. The above results suggest that retinal pigment epithelial cells and fibroblasts are major cellular components of PVR membranes, and that mesenchymal cells are major cellular components and glial cells are minor cellular components of PDR membranes.     

Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression

PURPOSE: To assess the incidence of cell proliferation and apoptosis in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and macular pucker (MP) and to further investigate the potential involvement of key executors of apoptosis. METHODS: Epiretinal membranes were obtained from the eyes of 23 patients who underwent vitrectomy surgery for recurrent retinal detachment due to PVR (n = 16), traction retinal detachment due to PDR (n = 5), and macular pucker (n = 2). Cell proliferation was evaluated by Ki-67 and PCNA (proliferation cell nuclear antigen) immunostaining. Apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transfrase-dUTP-nick end labeling). The expression of caspase-3 and PARP (poly-ADP-ribose-polymerase) was detected using antibodies against activated caspase-3 and p85 fragment of PARP. Cytokeratin and activated caspase-3/PARP, GFAP (glial fibrillary acidic protein) and activated caspase-3/PARP double staining were used to identify cell types in the membranes. RESULTS: There was no statistically significant difference in the cell proliferative index between PVR (70.1 +/- 4.2%), PDR (82.1 +/- 7.0%), and macular pucker (72.9 +/- 22.8%) by multivariate analysis (p = 0.39, ANOVA) and univariate analysis. Apoptotic nuclei were seen more frequently in chronic retinal detachments of greater than 2 months duration, but the difference, compared to shorter term retinal detachments was not statistically significant (p = 0.19). The apoptosis indices determined for PVR (2.3 +/- 0.7%), PDR (3.4 +/- 1.5%) and macular pucker (5.5 +/- 3.2%) were not significantly different (ANOVA, p = 0.41). Apoptotic nuclei were correlated, increased with expression of caspase-3 and PARP. Many apoptotic cells appeared to derive from retinal pigment epithelium cells. CONCLUSIONS: Cell proliferation and apoptosis appear to be key mechanisms regulating certain cell populations in epiretinal membranes of PVR, PDR, and macular pucker. Inhibition of proliferative regulators such as PCNA and/or activation of apoptotic executors such as caspase-3 may serve as therapeutic targets to halt progression of proliferative retinal disorders.     

Quantitative analysis of interleukin-6 in vitreous from patients with proliferative vitreoretinal diseases

PURPOSE: To explore immunological mechanisms in the pathogenesis of proliferative vitreoretinal diseases, we measured the concentration of interleukin-6 in the vitreous body and serum from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and premacular fibrosis. To evaluate immunological etiology, interleukin-6 levels in each disease were compared with disease severity. METHODS: Clinical samples were obtained at the beginning of pars plana vitrectomy from 30 eyes of 26 patients with PDR, 12 eyes of 12 patients with PVR, and 10 eyes of 10 patients with premacular fibrosis. Interleukin-6 was quantitated with an enzyme-linked immunosorbent assay. RESULTS: The levels of detectable interleukin-6 in the vitreous specimens ranged from 22.8 to 666.4 pg/mL in the PDR patients and from 28.2 to 416.3 pg/mL in the PVR patients. No interleukin-6 was detected in the vitreous specimens from patients with premacular fibrosis or in any serum samples from patients. Interleukin-6 levels of vitreous specimens from PDR patients were higher than those from PVR patients (P <.02, Mann-Whitney U-test). There was no correlation between clinical severity and interleukin-6 levels in vitreous specimens from either PDR or PVR patients. CONCLUSION: Our results indicated that cell-mediated immunity is involved in the pathogenesis of proliferative vitreoretinal diseases.     

Pathomorphology of membranes appearing in proliferative vitreoretinopathies

Immunohistochemical techniques were used to investigate the cell content of epiretinal membranes occuring in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Ten epiretinal membranes were obtained during surgery from eyes with PVR and five from eyes with PDR. This material was studied histopathologically and immunohistochemically. Retinal pigment epithelial cells, glial cells, macrophages, T lymphocytes and type IV collagen were identified in these membranes. The findings indicate that the cells mentioned possess a potential role in creating vitreoretinal membranes in PVR and PDR.     

增生性糖尿病视网膜病变和增生性玻璃体视网膜病变患者玻璃体中TGF-β2的表达及意义

Objective To observe the expression of transforming growth factor-β2 （TGF-β2） in the vitreous body of patients with proliferative vitreoretinal diseases; to investigate the role of TGF-β2 in the pathogenesis of proliferative vitreoretinal diseases. Methods In an experimental study, vitreous specimens were obtained during vitrectomy from 61 patients （61 eyes） with proliferative vitreoretinal diseases. The vitreous specimens were obtained from 37 eyes with proliferative diabetic retinopathy （PDR） and 24 eyes with proliferative vitreoretinopathy （PVR）. Eight vitreous fluid samples were obtained from a normal control group. The concentrations of TGF-β2 in the vitreous body were detected by enzyme-linked immunosorbent assay （ELISA）. Results The concentrations of TGF-β2 in the vitreous bodies of eyes with PDR, PVR and the normal controls were 22.71±2.32 ng/ml, 21.28±1.7）ng/ml, and 19.00±0.62 ng/ml, respectively. Intravitreous concentrations of TGF-β2 were higher in patients with PDR and PVR than in the control group. The difference was statistically significant（F=7.756, P<0.01）. The concentration of TGF-β2 in the vitreous body from eyes of PDR patients was clearly higher than concentrations in PVR patients. The difference was statistically significant （P<0.05）. The concentrations of TGF-β2 in the vitreous body were higher in level Ⅵ of the PDR group in comparison to level Ⅴ of the PDR group. The difference was statistically significant （P<0.01）. The concentrations of TGF-β2 in the vitreous body were higher in the D class of the PVR group in comparison to the C class. The difference was statistically significant （P<0.01）. The concentrations of TGF-β2 in the vitreous bodies were positively correlated with the duration of the diseases： the correlation for the PDR group was r=0.705 （P<0.01） and the correlation for the PVR group was r=0.934（P<0.01）. Conclusion TGF-β2 may play an important role in the pathogenesis and development of proliferative vitreoretinal diseases.     

三种视网膜病视网膜前膜中基质金属蛋白酶及其天然抑制分子的表达

目的 研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)、增殖性玻璃体视网膜疾病(proliferative vitreoretinopathy,PVR)和急性视网膜坏死(acute retinalnecrosis,ARN)患者视网膜前膜中基质金属蛋白酶(matrixmetalloproteinases:MMPs)及其天然抑制物(tissueinhibitorsofmetalloproteinages,TIMPs)的表达情况.方法 玻璃体手术中剥取PVR、PDR和ARN患者的视网膜前膜,同供体眼视网膜作为正常对照,冰冻切片后进行免疫组织化学染色,包括:MMP-1,MMP-2,MMP-3,MMP-7,MMP-9,TIMP-1和TIMP-2.结果 正常视网膜中能够观察到MMP-1,MMP-3,TIMP-1和TIMP-2的表达,在PVR、PDR和ARN患者标本中各种分子的表达都增强,尤以MMP-2,MMP-3和MMP-7明显.结论 正常视网膜中存在MMPs和TIMPs分子维持着细胞外基质动态的平衡,在PVR,PDR和ARN患者中MMP-2,MMP-3和MMP-7等MMPs分子表达增强,在其病变过程中可能起重要作用.     

增殖性玻璃体视网膜病变细胞凋亡的信号传导途径研究

目的 :探讨增殖性玻璃体视网膜疾病细胞凋亡的信号传导途径 ,以寻求新的药物治疗途径。方法 :2 3例增殖性玻璃体视网膜病变 (PVR) ,增殖性糖尿病性视网膜病变 (PDR) ,黄斑裂孔 (MH)及黄斑前膜 (MP)的视网膜前膜 (epiretinalmem brane,ERM )由玻璃体切割术中取得。细胞凋亡的情况由terminaldeoxynucleotidyltransfrase dUTP nickendlabeling(TUNEL法 )进行评估。Caspase 3及PARP的表达由特异性抗体抗活性Caspase 3和抗P 85片段的PARP检测。Cytokeratin与抗活性的Caspase 3双染色法进行凋亡细胞类型的鉴别。结果 :大多数发生凋亡的细胞为RPE细胞 ,而凋亡细胞与抗活性Caspase 3和抗P 85片段的PARP表达增加相关。细胞凋亡的数目与发生慢性视网膜脱离 (>2个月 )的病例有关 ,但凋亡系数 (apopto sisindex ,AI)在两组间无显著性差异 (1 4 4 2 9vs 3 2 2 86 ,P =0 1877)。PVR ,PDR ,MP各组的凋亡系数分别为 2 32 5 % ,3 4 2 % ,5 5 % ,P值分别为PPVR&PDR>0 1(0 16 85 ) ,PPDR&MP>0 1(0 5 380 ) ,PPVR&MP>0 1(0 8333)。结论 :此项研究发现细胞凋亡在PVR、PDR、MH及MP发病中的重要调节作用。诱导Caspase 3活性表达可作为一种治疗增殖性视网膜疾病的新的尝试     

Surgical outcomes of epiretinal membrane removal after successful pars plana vitrectomy for retinal diseases

PURPOSE: To evaluate visual outcomes after a removal of an epiretinal membrane (ERM) secondary to rhegmatogenous retinal detachment (RRD), proliferative vitreoretinopathy (PVR), or proliferative diabetic retinopathy (PDR). METHODS: The medical charts of 51 consecutive patients who underwent PPV to remove an ERM were reviewed in an institutional setting. The preoperative best-corrected visual acuity (BCVA) was evaluated to determine if it was a possible predictor of the postoperative BCVA. The visual outcomes in the RRD, PVR, and PDR groups were compared. Follow-up periods ranged from 13 to 90 months (mean, 40.9 months). RESULTS: After the ERM was removed, the postoperative BCVA improved significantly by 0.471 logarithm of the minimum angle of resolution units for all groups (t = 8.99; P < 0.001). The postoperative BCVA improved by two or more lines in 43 eyes (84.3%). Patient age and the preoperative BCVA significantly correlated with the visual improvement (P = 0.0082 and P = 0.035, respectively). CONCLUSION: The BCVA improves after removal of an ERM following PPV for eyes with RRD, PVR, or PDR. Patient age and preoperative BCVA correlated with the visual improvement after the ERM removal.     

硅油取出前视网膜脱离病因分析

目的；报告硅油取出前视网膜脱离发生率，并分析发生此视网膜脱离的有关病因。方法：选择增生性玻璃体视网膜病变（PVR）和增生型糖尿病视网膜病变患者行玻璃体切割联合硅油填充手术。结果：16眼中，有10眼在硅油取出前视网膜复位，6眼视网膜脱离，视网膜脱离发生率为37．5％，视力增进4眼（25％），不变8眼（50％），下降4眼（25％）。术后并发症为晶状体混浊加重（5眼，31％），继发性青光眼（2眼，13％），虹膜新生血管（1眼，6％），低眼压（2眼，13％），PVR加重（2眼，13％）。结论：硅油取出前视网膜脱离发生主要原因为原裂孔未封闭，新裂孔形成，视网膜表面增殖膜形成等。     

Oral sodium fluorescein to improve visualization of clear vitreous during vitrectomy for proliferative diabetic retinopathy

Purpose: To evaluate the efficacy and safety of orally administered sodium fluorescein to stain the clear vitreous before vitrectomy for proliferative diabetic retinopathy (PDR). Methods: Twenty‐two consecutive eyes of 20 patients with PDR and five eyes of five patients with proliferative vitreoretinopathy (PVR) were included. The average patient age was 52 years (range 46–58). Closed pars plana vitrectomy, proliferative membrane peeling and endolaser photocoagulation were performed. Vitreous and blood samples were collected to measure sodium fluorescein concentrations by high pressure liquefied chromatography. Results: The degree of staining of the clear vitreous was evaluated by colour photographs, videos and the concentration of sodium fluorescein in the vitreous and blood samples. The clear vitreous in all 22 eyes with PDR ranged from slightly to markedly green, but the clear vitreous in five eyes with PVR was not stained with sodium fluorescein. The sodium fluorescein concentration in the vitreous samples ranged from 122 to 282.0 ng/mL and from 64 to 74 ng/mL in the blood samples in patients with diabetes and PVR. No urticaria, nausea or other side‐effects developed. Conclusion: The clear vitreous can be stained markedly green by sodium fluorescein administered 12–16 h before surgery. Surgeons can easily differentiate residual clear vitreous. The stained vitreous may be made more visible by photocoagulation. This method is also helpful in teaching surgical procedures, and fewer side‐effects compared with intravenous and intravitreal fluorescein and intravitreal triamcinolone.     

Non-paralleled increase of hepatocyte growth factor and vascular endothelial growth factor in the eyes with angiogenic and nonangiogenic fibroproliferation

Vascular endothelial growth factor (VEGF) has been known as principal angiogenic factor in vasculogenesis, tumor angiogenesis and ocular angiogenesis. Currently, hepatocyte growth factor (HGF) has been reported to play a major role in ocular angiogenesis. We studied distribution of both growth factors in angiogenic and non-angiogenic fibroproliferation to determine the correlation of VEGF and HGF in retinal angiogenesis. Concentrations of VEGF and HGF molecules in vitreous samples from 27 eyes with angiogenic proliferative diabetic retinopathy (PDR) and 9 eyes with non-angiogenic proliferative vitreoretinopathy (PVR) were measured by enzyme-linked immunosorbent assay (ELISA). Vitreous samples with idiopathic macular role (IMH) served as a control. Concentrations of VEGF in the angiogenic PDR were 4.3 +/- 5.8 ng/ml (mean +/- SD), and were significantly higher than in non-angiogenic PVR (0.5 +/- 0.1 ng/ml). No significant differences were observed on VEGF concentrations between PVR to control. On the contrary, HGF concentrations were significantly higher in PVR (22.5 +/- 21.8 ng/ml) than in control (6.9 +/- 5.2 ng/ml), those of PDR (24.0 +/- 16.3 ng/ml) were also significantly higher than control. Among PDR samples, VEGF concentration was significantly higher than in the subgroup with higher angiogenic activity represented by iris neovascularization, although there were no significant differences on HGF concentration between the subgroups. Focal increases in HGF on fibroproliferation in the eye regardless of the involvement of angiogenesis were not in remarkable relation with angiogenic activity, unlike VEGF. These data suggested a more extensive role of HGF than VEGF strictly related to angiogenesis.     

Morphological study on the intraocular proliferative membrane of proliferative diabetic retinopathy and proliferative vitreoretinopathy

The membranes from 42 eyes with PDR and 8 eyes with PVR were removed during vitreous surgery. In 12 of those with PDR and 3 of the cases with PVR, the reproliferated membranes formed beneath silicone oil (SO) were removed and were histologically and immunohistochemically examined, using morphometrical quantitative analysis. In each case, area coefficient, fibrous content and the number of new vessels, and thick basement membranes, increased wall cells and multilayer basement membranes of new vessels were studied. In both PDR and PVR, the number of cells per unit area tended to be increased with the period of time after SO was injected, while the percentage of fibrous components did not change. The Percentage of occurrence of each type of new vessels was almost the same in both primary and reproliferative PDR membranes. In the primary proliferative PDR membranes, endothelial cell proliferation was found predominantly, while glial hyperplasia was predominant in the primary proliferated PVR membranes and the reproliferated membranes under SO of PDR and PVR.