Increased levels of N(ε)- Carboxy methyl lysine (N(ε)-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study.

PURPOSE: To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT). METHOD: Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done. RESULTS: Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant. CONCLUSION: Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy.

Antimyeloperoxidase antibody is a biomarker for progression of diabetic retinopathy.

AIM: To study the correlation between serum antimyeloperoxidase (MPO) antibody levels with severity of diabetic retinopathy (DR). METHODS: Study subjects included 60 consecutive cases of type 2 diabetes mellitus (DM): no diabetic retinopathy (NODR, n=20); nonproliferative DR (NPDR, n=20); proliferative DR (PDR, n=20) and 20 healthy controls. Best corrected visual acuity (BCVA) was measured on logMAR scale. Serum anti-MPO antibody levels were evaluated using ELISA IgG kit. Serum urea and creatinine was measured using standard protocol. Data were analysed statistically. RESULTS: Mean serum anti-MPO antibody (RU/ml) was 16.94 ± 4.85 in controls, 17.66 ± 4.78 in NODR, 21.51 ± 5.27 in NPDR and 37.27 ± 11.92 in PDR groups. On ANOVA, significant difference in visual acuity was found among the study groups (F=73.46, p<0.001). Serum anti-MPO antibody was correlated significantly with decrease in visual acuity (F=48.40, p<0.001), increase in serum urea (F=128.13, p<0.001) and creatinine (F=77.10, p<0.001). CONCLUSION: Increase in serum anti-MPO antibody levels correlate with increased severity of DR. Serum anti-MPO antibody may be a noteworthy biochemical marker for progression of retinopathy from nonproliferative to proliferative stage.

Identification and characterization of proliferative retinopathy-related long noncoding RNAs.

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases.

Kininogen 1 and insulin-like growth factor binding protein 6: candidate serum biomarkers of proliferative vitreoretinopathy.

BACKGROUND: The aim was to validate whether kininogen 1 (KNG1) or insulin-like growth factor binding protein 6 (IGFBP-6) are serum biomarkers of proliferative vitreoretinopathy (PVR). METHODS: Samples from vitreous and corresponding serum samples were collected from patients with PVR. The donor vitreous samples and serum samples from healthy volunteers and volunteers who had undergone vitrectomies for other conditions were used as controls. The samples were subsequently analysed using Western blotting (WB) and enzyme-linked immunosorbent assay. RESULTS: The Western blotting outcomes indicated both IGFBP-6 and KNG1 could be specifically detected in the vitreous and serum samples of patients with PVR. The concentrations of KNG1 and IGFBP-6 were significantly higher in both vitreous and serum samples from patients with severe PVR than in the samples from patients with moderate PVR. The serum concentrations of KNG1 or IGFBP-6 had decreased by the post-vitrectomy examinations. The receiver operating characteristic (ROC) analyses when the concentrations of IGFBP-6 or KNG1 were greater than 181.4 pg/ml or 441.75 ng/ml, respectively, predicted severe PVR with both a sensitivity and specificity of over 70 per cent. When the concentrations of IGFBP-6 or KNG1 were greater than 98.5 pg/ml or 88.5 ng/ml, respectively, they predicted the PVR prognosis with both a sensitivity and specificity of 80 per cent. CONCLUSIONS: KNG1 and IGFBP-6 may be candidate serum biomarkers of PVR.

Protection from sickle cell retinopathy is associated with elevated HbF levels and hydroxycarbamide use in children.

Elevated foetal haemoglobin (HbF) levels are protective against some manifestations of sickle cell anaemia but the impact on retinopathy is unknown. We report on 123 children with HbSS, 10.6% of whom developed retinopathy. Independent of hydroxycarbamide, children with a HbF <15% had 7.1-fold (95% confidence interval, 1.5-33.6) higher odds of developing retinopathy. In children treated with hydroxycarbamide, those with retinopathy had lower HbF levels compared to children without retinopathy (9% vs. 16%; P = 0.005). We report a protective benefit of elevated HbF regarding retinopathy, and our data suggests induction of HbF with hydroxycarbamide may prevent retinopathy in children.

Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy.

A role for vascular endothelial growth factor (VEGF) has been clearly implicated in the pathogenesis of proliferative diabetic retinopathy (PDR). However, other molecules and mechanisms may be operating independently, or in conjunction with VEGF in the pathogenesis of this disease. Therefore, we made an attempt to comparatively investigate the levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of subjects with Proliferative Diabetic Retinopathy (PDR) compared to control subjects. The vitreous and plasma concentrations of VEGF, EPO (Erythropoietin) and PEDF (Pigment Epithelium Derived Factor) were measured using Enzyme Linked Immunosorbent Assay (ELISA) and the postmortem retinal tissue was subjected to Western blot analysis. The mean vitreous and plasma levels of VEGF and EPO in patients with PDR were significantly (p<0.001) higher than those in subjects without diabetes. Conversely, the vitreous and plasma levels of PEDF were significantly (p<0.001) lower in the PDR patients compared to control subjects. Multivariate logistic-regression analyses indicated that EPO was more strongly associated with PDR than VEGF. The protein expression of the VEGF and EPO in the retinal tissue was significantly higher in PDR and diabetes without complication groups compared to controls. Compared to controls, the protein expression of PEDF was significantly lower in retinal tissues from diabetes patients without complications and in patients with PDR. The fact that the vitreous and plasma levels and the retinal tissue protein expression of EPO were strongly associated with PDR implies a definite role of 'hypererythropoietinemia' in neovascularization processes.

Anemia as a factor related to the progression of proliferative diabetic retinopathy after photocoagulation.

OBJECTIVE: This study aimed to investigate factors that could be related to the progression of proliferative diabetic retinopathy in patients treated with photocoagulation. METHODS: In this case-control study, a total of 106 patients with diabetic retinopathy participated who were treated with photocoagulation. We analyzed glycaemia, serum cholesterol, triglycerides, hemoglobin, platelet levels, blood pressure measurement, diabetes duration, diabetes and hypertension treatment, sex, and age. The statistical analysis was done with t test, χ² test, odds ratio (OR), and simple linear regression. RESULTS: We found statistical significance in blood glucose level(P=.038), cholesterol level (P<.001), and hemoglobin level (P<.001). The simple linear regression was significant with blood glucose level (P<.05) and hemoglobin level (P=.001). Hemoglobin had a significant result: OR=2.432, 95% CI 1.902-3.115; Pearson χ²=16.812; P<.001. CONCLUSIONS: Anemia is an important finding in diabetic patients. Anemia is a relevant factor related to the progression of proliferative diabetic retinopathy, which can be treated with photocoagulation.

[Kininogen-1 and insulin-like growth factor binding protein-6 as serum biomarkers for proliferative vitreoretinopathy].

OBJECTIVE: To evaluated the predictive potential of kininogen-1 and insulin-like growth factor binding protein-6 (IGFBP-6) for PVR. METHODS: Vitreous and serum samples were obtained from 24 PVR patients. Vitreous from 8 donated normal eyes, and serum samples from 20 healthy volunteers served as control. Patients who underwent vitrectomy with C(3)F(8) gas tamponade (n = 15) and silicone tamponade (n = 8) and patients who experienced recurrent retinal detachment after scleral buckling surgery (n = 8) were recruited for serum tests as well. Western blot analysis was employed to detect the presence of kininogen-1 and IGFBP-6. The protein concentration was measured by using enzyme linked immunosorbent assay (ELISA) analysis. All date were analyzed with the SPSS 3.0 for Windows (only-way analysis of variance and t test). RESULTS: Western blot analysis displayed that except that IGFBP-6 was absent in 2 PVR vitreous, both kininogen-1 and IGFBP-6 were otherwise found in all PVR vitreous and serum samples. Neither kininogen-1 nor IGFBP-6 can be detected in normal vitreous or serum samples. Protein expression was more intensive in severe PVR vitreous than in mild PVR vitreous, which was confirmed by a significantly higher concentration of each protein in sever PVR vitreous. The ELISA outcomes documented that kininogen-1 concentration in vitreous were significantly higher in severe PVR patients than those in mild PVR (281.0 ± 63.0 & 237.5 ± 32.1) µg/L (t = 5.44, P < 0.05). Kininogen-1 was about 2 times higher in serum than in vitreous (443.3 ± 190.1) µg/L (t = 5.27, P < 0.05). At 6 months after vitrectomy with gas tamponade in 15 patients, their kininogen-1 level in serum was significantly lower than that of preoperation (81.9 ± 18.6 & 443.3 ± 190.1) µg/L (t = 5.26, P < 0.05) and encircling failure group was (116.8 ± 45.1) µg/L, it was higher than that of normal and silicone tamponade groups (t = 3.95, 4.34;P < 0.05). Similarly, IGFBP-6 concentration in vitreous were significantly higher in severe PVR patients than those in mild PVR (352.9 ± 64.4 & 283.9 ± 69.9) ng/L (t = 5.08, P < 0.05) and its level in serum was (185.3 ± 34.9) ng/L and lower than that of in vitreous(t = 7.95, P < 0.05). At 6 months after vitrectomy with gas tamponade in 15 patients, their IGFBP-6 level in serum decreased comparing that of preoperation (65.4 ± 31.8) ng/L (t = 11.10, P < 0.05) and encircling failure group was (109.2 ± 6.6) ng/L, it was higher than that of normal and silicone tamponade groups (t = 3.16, 2.77; P < 0.05). CONCLUSIONS: Kininogen-1 and IGFBP-6 are presented in serum and vitreous in PVR patients. The strength of protein expression is related to the severity of PVR. These results suggested that kininogen-1 and IGFBP-6 can be biomarkers for severe PVR.

Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab.

AIMS: To determine the level of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the plasma of patients with proliferative diabetic retinopathy before and after an intravitreal injection of bevacizumab. METHODS: Eleven patients with type 2 diabetes and control of 30 non-diabetic patients were studied. The 11 eyes of 11 patients received an injection of bevacizumab (1.25 mg). Samples of blood were collected just before the injection, and after 1 day, 7 days and 1 month. The concentrations of VEGF and PEDF in the plasma were measured by ELISA. RESULTS: The VEGF concentration before the injection was 114.0 pg/ml. It was significantly reduced to 9.7 pg/ml after 1 day, to 11.7 pg/ml after 7 days and to 25.9 pg/ml even after 1 month (p<0.001, p<0.001, p<0.001, respectively). The PEDF concentration before the injection was 7.2 microg/ml. It was significantly reduced to 5.8 microg/ml after 1 day, to 5.8 microg/ml after 7 days and to 6.3 microg/ml after 1 month (p<0.001, p<0.001, p>0.05, respectively). CONCLUSIONS: The decreased levels of blood VEGF after an intravitreal injection of bevacizumab indicate that bevacizumab enters the general circulation and may also affect the PEDF levels. Thus, we should carefully examine patients for systemic changes and the fellow eye after an intravitreal injection of bevacizumab.

Preoperative duration of retinal detachment and subretinal immunoreactive endothelin-1: repercussion on logarithmic visual acuity.

PURPOSE: To analyze whether preoperative duration of primary rhegmatogenous retinal detachment (RD) influences endothelin-1 (ET-1)--a vasoactive, mitogenic, and pro-apoptotic peptide- levels with repercussions on logarithmic (LogMAR) visual acuity (VA). METHODS: Prospective clinical cohort study on 66 healthy patients [33 with proliferative vitreoretinopathy (PVR) and 33 with no PVR] with unilateral RD candidates for scleral buckling (SB) surgery. Using radioimmunoassay, immunoreactive ET-1 (IR-ET-1) was tested in both plasma and subretinal fluid (SRF) of these RD patients. Pearson's correlations were evaluated between preoperative RD duration and each IR-ET-1 level (plasma, SRF and the difference SRF minus plasma) and also between both variables and the LogMAR VAs (preoperative, postoperative 8 months, and the difference: postoperative 8 months minus preoperative). RESULTS: PVR was associated with higher preoperative RD duration, higher LogMAR VA values (pre- and postoperative 8 months) and higher IR-ET-1 values (plasma, SRF and the difference: SRF minus plasma) than no-PVR IR-ET-1 levels (plasma and SRF) were only correlated (r = 0.462, p = 0.007; r = 0.397, p = 0.022 respectively) with preoperative RD duration in the no-PVR group. IR-ET-1 values (plasma, SRF and the difference:SRF minus plasma) showed statistically significant correlations with pre- and with postoperative 8 months LogMAR VAs in no-PVR and with postoperative 8 months LogMAR VA and LogMAR VA difference in PVR The highest correlation between IR-ET-1 levels and LogMAR VAs was found between SRF IR-ET-1 and postoperative 8 months LogMAR VA in PVR (cases with macula-on) (r = 0.956, p < 0.0001). CONCLUSIONS: Preoperative RD duration showed statistically significant positive correlations with pre- and with postoperative 8 months LogMAR VAs in both the no-PVR and the PVR groups and with IR-ET-1 measurements (plasma and SRF: lower correlations) only in the no-PVR group. These findings support the idea of doing primary and prompt vitrectomy for RD and perhaps using coadjutant pharmacologic therapy in order to improve visual results.

Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases.

Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids from total of 345 patients with diabetic macular edema (DME, n = 92), proliferative diabetic retinopathy (PDR, n = 147), branch retinal vein occlusion (BRVO, n = 30), central retinal vein occlusion (CRVO, n = 13) and rhegmatogenous retinal detachment (RRD, n = 63). As a control, we selected a total of 83 patients with either idiopathic macular hole (MH) or idiopathic epiretinal membrane (ERM) that were free of major pathogenic intraocular changes, such as ischemic retina and proliferative membranes. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors: interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases (DME, PDR, BRVO, CRVO, and RRD) compared with control group. According to the correlation analysis in the individual patient's level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. Vascular endothelial growth factor (VEGF) was significantly elevated in patients with PDR and CRVO. In PDR patients, the elevation of VEGF was significantly correlated with the three factors: IL-6, IL-8, and MCP-1, while no significant correlation was observed in CRVO patients. In conclusion, multiplex bead system enabled a comprehensive soluble factor analysis in vitreous fluid derived from variety of patients. Major three factors: IL-6, IL-8, and MCP-1 were strongly correlated with each other indicating a common pathway involved in inflammation process in vitreoretinal diseases.

Components of the fibrinolytic system in the vitreous body in patients with vitreoretinal disorders.

PURPOSE: To assess components of the fibrinolytic system in the vitreous humour and serum of patients with vitreoretinal disorders. METHODS: Forty-three samples of vitreous humour and plasma of 43 patients undergoing pars plana vitrectomy for macular hole, macular pucker, retinal detachment or proliferative vitreoretinopathy were evaluated for their content of plasminogen, a2-antiplasmin, plasminogen-activatorinhibitor 1, plasmin-a2-antiplasmin-complex, tissue plasminogen activator, total protein, albumin, d-dimer. Patient groups were compared with each other using the U-test (Mann and Whitney) for non-parametric testing of two independent samples. RESULTS: The groups of retinal detachment and proliferative vitreoretinopathy had elevated vitreal levels of plasminogenactivator-inhibitor 1 (352.5 and 370.7 ng/mL vs. 1.86 and 56.6 ng/mL, P = non-significant), plasmin-a2-antiplasmincomplex (2416.5 and 1836.2 microg/L vs. 124.2 and 133.4 microg/L, P < 0.001), albumin (0.08 and 0.15 g/dL vs. 0.03 and 0.07 g/dL, P < 0.05) and d-dimer (4.76 and 1.64 microg/mL vs. 0.40 and 0.48 microg/mL, P = non-significant) when compared with patients with macular hole and macular pucker. CONCLUSIONS: There are significant differences in the vitreal concentration of components of the fibrinolytic system in patients with vitreoretinal disorders. Breakdown of the blood-retinal barrier and complex disease-specific mechanisms are thought to be responsible for an increase of components of the fibrinolytic system in the vitreous.

[Prevalence of diabetic retinopathy. Check-up program of a public health insurance company in Germany 2002-2004]. / Prävalenz der diabetischen Retinopathie. Studie bei Versicherten der Deutschen Betriebskrankenkasse 2002-2004.

OBJECTIVES: Population based studies have reported a prevalence of diabetic retinopathy (DR) at the time of diagnosis in up to 30% of the patients. In the context of a general diabetes check-up program (so called "Diabetes-TUV"), the prevalence of diabetic retinopathy in Germany was examined in all diabetes patients insured in a public health insurance company. METHODS: Patients were screened in the offices of 181 ophthalmologists according to a standardized protocol formulated by Prof. Kroll, Marburg. A total of 6,500 sheets were analysed out of which 14.5% were multiply documented. The latest protocols of 5,596 patients were evaluated; the mean age was 64.7 years with an average duration of diabetes of 10.2 years. RESULTS: Some 86.3% of the eyes examined had no DR, in 3.1% no evaluation was possible. Of the patients checked, 10.6% had DR. Mild/moderate DR was reported in 8.3%, severe non-proliferative DR in 1.7% and proliferative DR in 0.5%. Macular edema was reported in 0.85% of cases, vitreous hemorrhage in 0.2%. There was 0.1% iris neovascularisation and 0.1% retinal detachment. Visual impairment due to cataract or secondary cataract was found in 25.2% of patients with an 8.3% pseudophakia rate. CONCLUSION: Documentation of the eye examination in the diabetes check-up program was good. The 10.6% prevalence of DR in Germany, even after long standing diabetes, seems to be lower than in earlier population based studies in the US or UK. The data reported here could be an indication of better diabetes care in Germany. However, not all patients were examined with dilated pupils, and in the case of severe changes, the ophthalmologist might have decided not to fill in the report form and to have chosen another form of communication.

Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy.

PURPOSE: To determine levels of the chemokines CCL1/I-309, CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL7/MCP-3, CCL8/MCP-2, CXCL5/ENA-78, CXCL6/GCP-2, CXCL10/IP-10, and CXCL11/I-TAC in the vitreous humor and serum, from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD), and to investigate the expression of MCP-1, CXCL12/SDF-1, and the chemokine receptor CXCR3 in epiretinal membranes. METHODS: Paired vitreous humor and serum samples were obtained from patients undergoing vitrectomy for the treatment of RD (57 specimens), PVR (32 specimens), and PDR (88 specimens). The levels of chemokines were measured by enzyme-linked immunosorbent assays. Eighteen PDR and 5 PVR membranes were studied by immunohistochemical techniques. RESULTS: Of all the chemokines studied, only MCP-1 and IP-10 were detected in vitreous humor samples. MCP-1 levels in vitreous humor samples were significantly higher than in serum samples (p < 0.001). MCP-1 levels were significantly higher in vitreous humor samples from patients with PVR and PDR compared with RD (p = 0.0002). MCP-1 levels in vitreous humor samples from patients with active PDR were significantly higher than in inactive PDR cases (p = 0.0224). IP-10 levels in vitreous humor samples were significantly higher than in serum samples (p = 0.0035). IP-10 levels were significantly higher in vitreous humor samples from patients with PVR and PDR compared with RD (p = 0.0083). The incidence of IP-10 detection in vitreous humor samples was significantly higher in active PDR cases compared with inactive cases (p = 0.0214). There was a significant association between the incidence of IP-10 detection and increased levels of MCP-1 in vitreous humor samples from all patients, and patients with RD and PDR (p < 0.001 for all comparisons). MCP-1, and SDF-1 were localized in myofibroblasts in PVR and PDR membranes and in vascular endothelial cells in PDR membranes. CXCR3 was expressed by vascular endothelial cells in PDR membranes. CONCLUSION: MCP-1, IP-10 and SDF-1 may participate in pathogenesis of PVR and PDR. Myofibroblasts and vascular endothelial cells are the major cell types expressing MCP-1, SDF-1, and CXCR3 in epiretinal membranes.

[Diagnostic and therapeutic options in diabetic retinopathy]. / Diagnostik und Therapie der diabetischen Retinopathie Schicken Sie lhre Diabetiker regelmässig zur Fundoskopie.

Diabetes mellitus is the systemic disease that most often leads to blindness. Since the diminishment of visual acuity is a late symptom of the disease, screening examinations are of particular importance, as only in this way can the optimal time point for treatment be determined. Stage-oriented laser therapy prevents blindness due to macular edema or proliferative diabetic retinopathy. For a number of years, vitreoretinal surgery has enabled the treatment of late ocular manifestations such as bleeding into the vitreous body and traction retinal detachment. With appropriate stage-oriented treatment, hopeless cases of diabetic retinopathy ending in blindness should become the exception. The only useful and confirmed effective medical treatment capable of delaying this late complication continues to be careful blood glucose and blood pressure control.

Fibrinogen and detached retina with or without proliferation.

PURPOSE: Fibrinogen is a multifunctional molecule, participating in processes such as wound healing, inflammation and cell proliferation. Therefore a comparative study of plasma fibrinogen levels was performed on patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy after RRD (PVR). METHOD: Plasma fibrinogen levels were measured preoperatively in three groups of patients; twenty-two (n=22) patients from the ORL department of our hospital, serving as a control group; twenty-eight (n=28) patients with RRD; and twenty (n=20) patients with PVR after RRD. Patients' ages were matched for all three groups; diabetics and patients with cardiovascular disease were excluded. T-Student's test was performed for the comparison of the plasma fibrinogen mean values of the aforementioned groups. RESULTS: Statistically significant (p value: 0.013) elevation of fibrinogen plasma levels was observed in patients with RRD compared to those of the control group. In addition, patients with PVR had significantly higher plasma fibrinogen levels (p value: 0.03) than RRD patients. CONCLUSION: The results suggest a correlation between fibrinogen plasma levels and the development of RRD and PVR.

[Analysis of retinoic acid in subretinal fluid in patients with rhegmatogenous retinal detachment].

To investigate the relationship between the level of retinoic acid (RA) in the subretinal fluid (SRF) and the extent of the vitreoretinopathy in 56 patients with rhegmatogenous retinal detachment, we studied the levels of RA in both SRF and serum using high liquid chromatography and also examined those levels in part of patients who took oral vitamin A 150,000 U.d-1. The results were that the level of RA in the SRF increased with the grade of the proliferative vitreoretinopathy (PVR); the levels of RA in both SRF and serum were significantly higher in the cases with vitamin A than those without. We conclude that retinoic acid metabolism between retinal pigment epithelial cells and neural epithelia was unbalanced after retinal detachment. Oral vitamin A is helpful to inhibit the genesis and development of the proliferative vitreoretinopathy.

Monocyte chemotactic protein-1 in proliferative vitreoretinal disorders.

PURPOSE: To investigate whether the chemokines monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are involved in the pathogenesis of proliferative vitreoretinal disorders and to study their possible interaction with IL-6. METHODS: In a prospective study of 125 consecutive patients (125 eyes), vitreous and paired serum samples were obtained and were assayed for MCP-1 and IL-8. Levels of IL-6 were determined by proliferation of the IL-6-dependent hybridoma cell line 7TD1. RESULTS: Monocyte chemotactic protein-1 was detected in 13 (48%) of 27 vitreous samples from patients with retinal detachment, in five (63%) of eight samples from patients with macular pucker, in 31 (72%) of 43 samples from patients with proliferative vitreoretinopathy, and in 32 (76%) of 42 samples from patients with proliferative diabetic retinopathy, but not in samples from five patients with idiopathic epiretinal membrane. There was a significant (P = .049) correlation between the incidence of MCP-1 detection in retinal detachment, macular pucker, and proliferative vitreoretinopathy groups and the severity of proliferation. Interleukin-8 was detected in two vitreous samples from eyes with retinal detachment, in two samples from eyes with proliferative vitreoretinopathy, and in three samples from eyes with proliferative diabetic retinopathy. Monocyte chemotactic protein-1 levels in the vitreous samples were positively correlated with IL-6 levels (r = .31, P = .01). Interleukin-6 levels were significantly (P = .0097) greater in vitreous samples with than without detectable levels of MCP-1. CONCLUSION: Monocyte chemotactic protein-1 is present in a substantial percent of vitreous samples from eyes with proliferative vitreoretinal disorders and may help in stimulating the infiltration of monocytes and macrophages into eyes with these disorders.