Vitreous levels of intercellular adhesion molecule 1 (ICAM-1) as a risk indicator of proliferative vitreoretinopathy

AIM: To investigate whether high vitreous levels of the soluble intercellular adhesion molecule 1 (sICAM-1) may be related to clinical risk factors of proliferative vitreoretinopathy (PVR) and whether their measurement may serve as an additional risk indicator of this complication in eyes with rhegmatogenous retinal detachment (RRD). METHODS: Levels of sICAM-1 were measured by enzyme linked immunosorbent assays (ELISA) in vitreous from 36 eyes with RRD clinically considered to be at high risk of developing PVR (large retinal breaks, vitreous haemorrhage, long standing RRD, and previous vitreoretinal surgery). Levels of sICAM-1 in this group were compared with those in vitreous from 31 eyes with RRD without clinical risk factors for PVR, 32 eyes with established PVR and 10 eyes with macular holes. RESULTS: Vitreous from eyes with RRD at high risk of developing PVR contained significantly higher levels of sICAM-1 (range 6.1-97.7 ng/ml; Mann-Whitney test, p=0.0002) than those from eyes with RRD at low risk of developing this complication (range 4.8-17.7 ng/ml). Vitreous sICAM-1 levels in eyes with RRD at high risk of developing PVR were significantly lower than in eyes with established PVR (p=0.037), but higher than in eyes with macular holes (p <0.0001). Levels of sICAM-1 >/=15 ng/ml (3 x median of the levels present in control eyes) provide a useful cut off point for a highly specific test (96.7%) with high positive (91.6%) and negative (96.7%) predictive values, despite a relatively low sensitivity (30. 5%). CONCLUSIONS: The present findings suggest that laboratory measurement of sICAM-1 levels in vitreous from eyes with RRD may constitute an additional factor for identifying patients at high risk of PVR. Hence, determination of sICAM-1 levels may aid in the monitoring of patients likely to develop this complication and in the identification of patients who may benefit from adjuvant anti-inflammatory therapy.     

Tenascin-C levels in the vitreous of patients with proliferative vitreoretinopathy

PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2-127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.     

Interleukin-8, nitric oxide and glutathione status in proliferative vitreoretinopathy and proliferative diabetic retinopathy

PURPOSE: To evaluate interleukin-8 (IL-8), nitric oxide (NO) and glutathione (GSH) profiles in vitreous humor and blood samples in patients with proliferative diabetic retinopathy (PDR) and in patients with proliferative vitreoretinopathy (PVR) and to compare the levels with those of controls. PATIENTS AND METHODS: NO concentrations were determined by using the Greiss reaction in plasma and vitreous humor samples. GSH levels were determined in both blood and vitreous humor samples, using DTNB, a disulfide chromogen. Vitreous IL-8 were assayed by ELISA. Twenty-three patients with PDR, 18 patients with PVR and 21 cadavers as the control group were included in the study. RESULTS: Plasma and vitreous NO levels were found to be 25.6 +/- 2.1 and 36.9 +/- 3.0 micromol/l in patients with PDR, 27.0 +/- 4.7 and 34.3 +/- 2.9 micromol/l in patients with PVR and 17.4 +/- 2.7 and 15.9 +/- 1.4 micromol/l in controls, respectively. Vitreous humor and plasma NO levels did not show any statistically significant difference between PDR and PVR groups. However, the values for vitreous in both groups were significantly higher than those of controls (p < 0.0001). Although IL-8 levels in vitreous samples of patients with PDR were not significantly different (79.6 +/- 9.7 pg/ml) from those of patients with PVR (42.2 +/- 7.3 pg/ml) (p = 0.06), the levels in both groups were significantly higher than those of controls (19.0 +/- 3.9 pg/ml) (p < 0.0001 and p < 0.05, respectively). Blood and vitreous GSH levels were found to be 5.3 +/- 0.4 micromol/g. Hb and 0.58 +/- 0.16 micromol/l in patients with PDR and 8.4 +/- 0.5 micromol/g. Hb and 15.7 +/- 2.2 micromol/l in patients with PVR and 12.0 +/- 1.1 micromol/g. Hb and 0.26 +/- 0.03 mmol/l in controls, respectively. Vitreous and blood GSH levels were significantly lower in patients with PDR compared to those with PVR (p < 0.0001 for both). CONCLUSION: Elevated levels of vitreous and plasma NO and vitreous IL-8 in PDR and PVR implicate a role for these parameters in the proliferation in these ocular disorders. GSH concentrations both in vitreous and blood samples of the PVR and PDR patients were much less than those observed in the control group. Lower GSH concentrations detected in PDR in comparison with those in PVR in vitreous humor and to a lesser degree in blood may play an important role in pathogenesis of new retinal vessel formation in patients with PDR. This also suggests that oxidative stress may be involved in the pathogenesis of PVR and particularly that of 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.     

Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative diabetic retinopathy

AIMS: To assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: MIF levels were assayed in the vitreous and paired serum samples of 73 consecutive patients with PDR (32 eyes) and macular hole or idiopathic epiretinal membrane (controls, 41 eyes). An enzyme linked immunosorbent assay technique was used to determine the concentrations of MIF. RESULTS: The median vitreous level of MIF was 11.93 ng/ml (range 4.16-103.85) in the patients with PDR, and 1.79 ng/ml (undetectable-8.93) in the controls. Vitreous levels in eyes with PDR were significantly greater than those in the controls (p<0.0001). Vitreous levels were significantly higher than serum levels in eyes with PDR (p=0.0026). MIF levels were significantly higher in the vitreous of PDR patients with severe fibrous proliferation than in those with slight proliferation (p<0.05). CONCLUSION: The results indicate increased levels of MIF in the vitreous of patients with PDR and a significant association between MIF levels and grades of fibrous proliferation, suggesting the possibility that MIF may play a part in the development of the proliferative phase of PDR.     

Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the correlation between monocyte chemotactic protein-1 (MCP-1) levels in the vitreous and clinical findings in eyes with proliferative diabetic retinopathy (PDR). METHODS: We assayed MCP-1 levels by ELISA in vitreous samples of 88 consecutive patients with PDR (52 eyes) and macular holes or idiopathic epimacular membrane (controls, 36 eyes). RESULTS: The level of MCP-1 in the vitreous was 2,097.5 +/- 1,099.4 pg/ml (mean +/- SD) in PDR, and 504.3 +/- 405.6 pg/ml in the controls. In PDR eyes, multivariate regression analysis revealed a significant association between MCP-1 levels in the vitreous and the degree of proliferative membrane, and a significant negative association between MCP-1 levels and the extent of preoperative retinal photocoagulation. CONCLUSION: The results suggest that MCP-1 may play a role in the development of the proliferative phase of PDR.     

Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative vitreoretinopathy

PURPOSE: To assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative vitreoretinopathy. METHODS: We assayed MIF levels in vitreous and paired serum samples of 74 consecutive patients with proliferative vitreoretinopathy (26 eyes), rhegmatogenous retinal detachment (22 eyes), and macular hole or idiopathic epiretinal membrane (control, 26 eyes) by enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of MIF were 51.33 +/- 49.21 ng/ml (mean +/- SD) in proliferative vitreoretinopathy, 19.11 +/- 16.13 ng/ml in rhegmatogenous retinal detachment, and 2.98 +/- 2.55 ng/ml in the controls. The vitreous levels in eyes with proliferative vitreoretinopathy were significantly higher than levels in eyes with rhegmatogenous retinal detachment (P = .0005) and in the control subjects (P < .0001). The vitreous levels were significantly higher than the serum levels in proliferative vitreoretinopathy (P < .0001) and rhegmatogenous retinal detachment (P = .0019), respectively. CONCLUSIONS: The results suggest that MIF may be involved in the pathogenesis of proliferative vitreoretinopathy.     

增殖性糖尿病视网膜病变玻璃体SDF-1和VEGF的含量分析

研究增殖性糖尿病视网膜病变患者玻璃体基质细胞衍生因子（Stromalcell—derivedfactor-1。SDF-1）和血管内皮生长因子（Vascularendothelialgrowthfactor，VEGF）的浓度，及其相互作用关系。方法：酶联免疫吸附法（Enzyme-linkedimmunosorbentassay，ELISA）检测玻璃体内SDF-1和VEGF的含量，每个标本重复3次。实验组为增殖性糖尿病视网膜病变（Proliferativediabeticretinopathy，PDR）的住院患者30例，对照组为同期行玻璃体切除术的特发性黄斑裂孔患者12例。结果：PDR患者玻璃体VEGF的平均浓度为（2865．87±387．85）pg／ml，明显高于特发性黄斑裂孔组[（142．42±21．03）pg／ml，P〈0．0001]。增殖性糖尿病视网膜病变患者玻璃体SDF-1的含量平均为（298．40±24．57）pg／ml，对照组为（86．9l±15．89）pg／ml，两组的差异具有统计学意义（P〈0．0001）。在30例PDR患者玻璃体内VEGF和SDF-1的含量表现为正相关（Pearson相关系数r=0．62，P〈0．001）。结论：增殖性糖尿病患者玻璃体SDF-1和VEGF的含量均高于非糖尿病患者，提示SDF-1和VEGF共同参与了增殖性糖尿病视网膜病变患者病理性新生血管的形成过程。     

Prostanoids in the vitreous of diabetic and nondiabetic human eyes with retinal detachment

We measured prostaglandin E2 (PGE2) and prostacyclin levels in the vitreous bodies of 5 eyes of patients with diabetic retinopathy complicated by rhegmatogenous retinal detachment (RRD) and compared them with the corresponding levels in 9 nondiabetic eyes with the same condition as well as with 10 control eyes of deceased patients with no known ocular pathology. We also studied the effect of surgical retinal reattachment on vitreal PGE2 and prostacyclin levels in 4 eyes. Vitreal samples from both nondiabetic and diabetic eyes with RRD were obtained during vitrectomy, while samples from deceased subjects (controls) were obtained 2-6 h after death. Vitreal PGE2 and prostacyclin levels in the control eyes approximated plasma levels (79.9 +/- 20.5 and 124.5 +/- 38.5 pg/ml, means +/- SD, respectively), while RRD in the nondiabetic eyes was associated with increased levels of both PGE2 and prostacyclin (3,170 +/- 3,024 and 467 +/- 283 pg/ml, respectively). In the diabetic eyes with diabetic retinopathy complicated by RRD, all of which underwent retinal photocoagulation, PGE2 and prostacyclin levels were 2-4 times lower than those of the nondiabetic eyes with detached retina. Following surgical retinal reattachment, vitreal levels of both components in diabetics and nondiabetics showed a reduction suggesting that the surgical procedure for obtaining vitreal samples was not the cause for elevated prostaglandin levels in the eyes with detached retina. We showed that RRD is associated with an excessive accumulation of PGE2 and prostacyclin in the vitreous, which is higher in nondiabetic than in diabetic eyes, indicating that diabetic retinopathy in laser-treated eyes might lead to reduced vitreal levels of these metabolites.     

Correlation of complement fragment C5a with inflammatory cytokines in the vitreous of patients with proliferative diabetic retinopathy

Purpose

To determine the vitreous concentration of complement fragment C5a in patients with proliferative diabetic retinopathy (PDR) and the relation between C5a and inflammatory cytokines including vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1).

Methods

Vitreous samples were obtained at the time of vitrectomy from 12 eyes of 11 PDR patients and from 11 eyes of 11 patients without diabetes with macular disease (controls). Vitreous and serum concentrations of human C5a, VEGF, and MCP-1 were quantified using FACS Caliber® flow cytometer.

Results

Vitreous concentration of C5a increased significantly in patients with PDR [median (range): 928.7 (46.6 to 3,319.4) pg/ml] compared with controls [58.7 (22.2 to 1,432.4) pg/ml; p?<?0.01]. In PDR patients, vitreous concentration of C5a correlated significantly with those of VEGF (p?<?0.05) and MCP-1 (p?<?0.05).

Conclusions

Our results suggest that C5a may play an important role in the pathogenesis of PDR and work in concert with inflammatory cytokines such as VEGF and MCP-1 in pathological angiogenesis.     

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.     

Increased intravitreal angiopoietin-2 levels associated with rhegmatogenous retinal detachment

Purpose

To explore factors related to pathogenesis of rhegmatogenous retinal detachment (RRD) and development of proliferative vitreoretinopathy (PVR), vitreous levels of angiopoietin-1 and ?2 (Ang-1 and ?2), previously undefined in RRD, transforming growth factor-(TGF) β1, vascular endothelial growth factor (VEGF), erythropoietin (EPO) and proteolytic mediators of extracellular matrix remodelling (MMP-2 and ?9) were compared in eyes with RRD and eyes with idiopathic macular hole or pucker.

Methods

Vitreous samples were collected from 117 eyes with RRD (study group) and 40 eyes with macular hole or pucker (control group). Growth factors were measured by ELISA and matrix metalloproteinases (MMPs) by gelatin zymography.

Results

The mean vitreous concentrations of Ang-2, MMP-2, and MMP-9 were higher (all p?<?0.01), whereas concentration of VEGF was lower (p?=?0.01) in eyes with RRD relative to controls. Logistic regression analysis identified Ang-2 concentration as a novel marker of RRD (p?=?0.0001, OR 48.7). Ang-1, EPO, and total TGF-β1 levels were not significantly different between the groups. However, TGF-β1 and MMP-2 were increased in eyes with total RRD compared to those with local RRD (p?≤?0.05). In eyes with PVR, no differences were observed in any studied marker as compared with non-PVR eyes.

Conclusions

Current results reveal Ang-2 as a key factor upregulated in RRD. It may co-operate with fibrosis-associated factors and contribute to vascular complications such as breakdown of blood–eye barrier and PVR development.     

PDR行玻璃体手术前注射雷珠单抗或曲安奈德后玻璃体腔内细胞因子的变化

目的：比较增生型糖尿病视网膜病变(PDR)行玻璃体切割术前用雷珠单抗或曲安奈德玻璃体腔内注射前后玻璃体腔内细胞因子的变化。

方法：前瞻性研究。将2015-05/2017-02我院收治的PDR患者88例112眼纳入研究。依照随机方法分为行玻璃体切割术前玻璃体腔注射0.5mg/0.05mL雷珠单抗组(43例57眼)、行玻璃体切割术前玻璃体腔注射4mg/0.1mL曲安奈德组(45例55眼),两组患者分别在玻璃体腔注射药物前抽取0.5mL玻璃体液后于玻璃体腔内注射雷珠单抗或曲安奈德。注药后7d行玻璃体切割术术前再次抽取玻璃体液0.5mL。采用双抗酶联免疫吸附试验(ELISA)测定玻璃体液的胎盘生长因子(PIGF)。用Luminex200液相芯片分析系统检测单核细胞趋化蛋白1(MCP-1)、单核细胞趋化蛋白3(MCP-3)、白介素-6(IL-6)、白介素-8(IL-8)、血小板源性生长因子-AB/BB(PDGF-AB/BB)和血管内皮生长因子-A(VEGF-A)浓度。

结果：雷珠单抗组玻璃体腔内PIGF与VEGF-A水平注射后较注射前均明显降低,而IL-6、IL-8水平增高(PIGF：65.36±15.16 vs 19.42±6.34pg/mL; VEGF-A：315.16±14.34 vs 21.32±2.54pg/mL,IL-6：37.32±4.04 vs 52.42±5.32pg/mL; IL-8：111.723±21.32 vs 198.73±19.03pg/mL,P<0.001)。而MCP-1、MCP-3及PDGF-AB/BB的水平无明显变化(P>0.05)。曲安奈德组玻璃体腔内PIGF水平显著增加(74.28±17.34 vs 136.12±15.34pg/mL,P<0.05)。而MCP-1水平明显减少(2789.32±143.54 vs 2038.21±105.34pg/mL,P<0.05)。MCP-3、IL-6、IL-8、PDGF-AB/BB、VEGF-A表达均无明显改变(P>0.05)。两组患者治疗后进行对比,雷珠单抗注射后玻璃体中PIGF、VEGF-A含量明显低于曲安奈德注射后含量(P<0.01),IL-8、MCP-1水平则显著增加(P<0.05)。此外,雷珠单抗组术中出血情况明显低于曲安奈德组(P<0.05)。

结论：玻璃体腔注射雷珠单抗能显著降低PIGF、VEGF-A表达,同时促进IL-6、IL-8水平增加; 而玻璃体腔内注射曲安奈德能减少MCP-1表达,促进PIGF水平增加。     

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.     

Correlation of matrix metalloproteinase levels with the grade of proliferative vitreoretinopathy in the subretinal fluid and vitreous during rhegmatogenous retinal detachment

Purpose: We investigated the activity of matrix metalloproteinase (MMP)‐2 and ‐9 and their latent pro‐forms (proMMP‐2, ‐9), and protein levels of MMP‐1, ‐3, ‐8 and tissue inhibitor of MMPs (TIMP)‐1 in the subretinal fluid (SRF) and vitreous of patients with rhegmatogenous retinal detachment (RRD). Potential correlations with proliferative vitreoretinopathy (PVR) grade were determined. Methods: Thirty‐seven SRF and 32 vitreous samples from RRD patients and nine vitreous samples from human organ donors (controls), were collected and assayed for MMP‐1, ‐3, ‐8/TIMP‐1 levels using enzyme‐linked immunosorbent assay (ELISA), and for proMMP‐2, ‐9, MMP‐2, ‐9 activity employing gelatine zymography. Results: ProMMP‐2, ‐9, MMP‐1, ‐3, ‐9, TIMP‐1 were significantly higher in the SRF and vitreous of RRD patients compared to the vitreous of organ donors. MMP‐8 levels were higher in RRD patients’ SRF. Regarding PVR grade, MMPs and TIMP‐1 were differentially present in SRF and vitreous. PVR grade correlated significantly with the levels of MMP‐2 in SRF, while proMMP‐2, MMP‐1, ‐2, ‐3, ‐8, ‐9 and TIMP‐1 levels correlated with PVR grade in the vitreous. Conclusion: MMP/TIMP‐1 levels are elevated in SRF and vitreous during RRD. Significant correlations between PVR grade and MMP‐2 in SRF and proMMP‐2, MMP‐1, ‐2, ‐3, ‐8, ‐9 and TIMP‐1 levels in vitreous were revealed. Investigation of MMP activity in vitreous may provide more valid conclusions compared to SRF pertaining to the role of the MMPs during RRD. The observations of the present study suggest a possible role for MMPs and TIMP‐1 in PVR pathophysiology.     

Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes

PURPOSE: Diabetic retinopathy and glaucoma are the primary causes of acquired blindness. Cytokines including transforming growth factor (TGF)-beta may be involved in these diseases. We therefore collected aqueous humor samples from patients with glaucoma and/or diabetes who were undergoing surgery, and determined the concentration of TGF-beta. METHODS: Aqueous humor samples were collected from 80 patients (84 eyes), including 19 eyes with primary open-angle glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated with POAG. Twenty-five eyes with cataract served as controls. The concentration of TGF-beta1 or TGF-beta2 was measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of TGF-beta1 was less than 0.1 pg/mL in all of the groups. In contrast to controls who had 1001.4 +/- 444.1 pg/mL, the concentration of total TGF-beta2 in the diabetes group was 1715.6 +/- 882.1 pg/mL, and that in the diabetes complicated with POAG group was 1692.9 +/- 361.9 pg/mL. These were significantly higher than that in controls. In contrast to the controls who had 321.2 +/- 197.9 pg/mL, the concentration of mature TGF-beta2 with POAG was 822.5 +/- 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 +/- 648.4 pg/mL. These were significantly higher than that in the controls. The eyes with diabetes complicated with POAG also had a significantly higher concentration than the eyes with diabetes alone. CONCLUSION: Total TGF-beta2 and mature TGF-beta2 in high concentration may correlate with progression of POAG, diabetes, and diabetes complicated with POAG.     

Balance of vascular endothelial growth factor and pigment epithelial growth factor prior to development of proliferative vitreoretinopathy

BACKGROUND: Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) are imbalanced in eyes with proliferative diabetic retinopathy or proliferative vitreoretinopathy (PVR). It is not known whether such an imbalance is already present in early PVR stages. We therefore analyzed VEGF and PEDF concentrations in subretinal fluids prior to PVR development. METHODS: A large number (n = 137) of subretinal fluid samples were obtained at the time of scleral buckling surgery for rhegmatogenous retinal detachment (RRD). Thirty patients developed PVR within 6 months after surgery. One hundred and seven patients undergoing the same surgery but without complications served as controls. Furthermore, vitreous from 16 patients with macular hole or pucker (MHP) served as reference for baseline intraocular concentrations. PEDF and VEGF concentrations were measured by commercial ELISAs. RESULTS: PEDF levels were substantially higher (9.6 microg/ml) compared to MHP vitreous (0.3 microg/ml, p < 0.001). VEGF levels were also higher (RRD: 0.07 ng/ml; MHP: 0.01 ng/ml, p < 0.05). Subretinal concentrations were not significantly different between PVR and control RRD patients. CONCLUSIONS: Although both VEGF and PEDF are increased at first surgery for RRD, they do not predict PVR development later on. The high PEDF concentrations and its known antiangiogenic activity suggest a protective role against neovascularization.     

Increased glutamate levels in the vitreous of patients with retinal detachment

Experimental models have implicated glutamate in the irreversible damage to retinal cells following retinal detachment. In this retrospective study we investigated a possible role for glutamate and other amino acid neurotransmitters during clinical rhegmatogenous retinal detachment (RRD). Undiluted vitreous samples were obtained from 176 patients undergoing pars plana vitrectomy. The study group consisted of 114 patients (114 eyes) with a rhegmatogenous retinal detachment. Controls included 52 eyes with an idiopathic macular hole or idiopathic epiretinal membrane and 10 eyes with a traction retinal detachment due to proliferative diabetic retinopathy. Vitreous concentrations of glutamate, gamma-aminobutyric acid (GABA), taurine, glycine, and aspartate were determined by high-pressure liquid chromatography (HPLC). Multivariate analysis was used to examine a possible association between amino acid neurotransmitter levels and several clinical variables including visual acuity. The mean vitreous concentration of glutamate in eyes with a rhegmatogenous retinal detachment (16.6 +/- 5.6 microM) was significantly higher as compared to the controls (13.1 +/- 5.2 microM) (P = 0.001). Taurine levels were also increased in RRD, whereas no significant difference could be observed in glycine, aspartate and GABA levels when comparing RRD with controls. A correlation was found between increased vitreous glutamate and a lower pre-operative visual acuity. No association was, however, observed between post-operative visual acuity and the level of any of the five amino acid neurotransmitters. RRD was associated with a significantly increased vitreous glutamate concentration. Using visual acuity as a functional parameter in this study, we could not demonstrate a correlation between vitreous glutamate, or any of the other tested amino acid neurotransmitters and visual outcome.     

The fellow eye of patients with rhegmatogenous retinal detachment

OBJECTIVE: To determine how often the fellow eyes of patients with rhegmatogenous retinal detachment (RRD) without proliferative vitreoretinopathy (PVR) harbor vision-threatening conditions at presentation and during follow-up. DESIGN: Retrospective, observational case series. PARTICIPANTS: Two hundred forty-eight patients with RRD without PVR were studied. INTERVENTION: The authors observed the fellow eye of patients with RRD for vision-threatening pathology. MAIN OUTCOME MEASURE: Detection of vision-threatening pathology in the fellow eye of patients with RRD without PVR. RESULTS: Two hundred forty-eight patients were observed for an average of 5.2 years. One hundred fifty-seven vision-threatening events or diagnoses occurred in the fellow eye, including pre-existing and newly diagnosed conditions, 97 (62%) of which were rhegmatogenous in nature. Fifty-six patients (23%) had retinal detachments in their fellow eye, including those with a history of RRD repair (28 eyes), those presenting with bilateral RRD (4 eyes), and those developing new RRD during follow-up (24 eyes). In addition, 1 patient developed recurrent retinal detachment in the fellow eye during follow-up. Retinal tears were diagnosed and treated with laser retinopexy or cryotherapy in 30 (12%) fellow eyes (4 before the initial examination, 7 upon initial examination, and 19 on follow-up). Lattice degeneration was present in 27 (11%) fellow eyes. CONCLUSIONS: Patients who develop RRD are at considerable risk for developing vision-threatening events, particularly rhegmatogenous events, in the fellow eye.