A stepwise implementation of the Slovenian National Diabetic Retinopathy Screening Program - evaluation of the first 4.5 years.

BACKGROUND: This retrospective cohort study aimed to assess the characteristics of patients enrolled in the national diabetic retinopathy (DR) screening program and evaluate the selected program's quality elements in the first five years after implementation. METHODS: Patients who underwent DR screening between February 2018 and June 2022 at the University Medical Centre Ljubljana were included. General patient characteristics (age, sex, type and therapy of diabetes mellitus (DM), duration of DM, blood HbA1c levels), best corrected visual acuity, stage of DR, presence of sight-threatening diabetic retinopathy (STDR), and selected quality indicators (quality of photographs, re-screening interval, time to treatment) were recorded and evaluated. RESULTS: A total of 34 654 screening examinations were performed on 13 513 patients with diabetes. The majority (77.3%) had Type 2 diabetes, with a mean DM duration of 9.74 ± 9.87 years. In 55.9% of patients, DM duration was less than ten years, and the mean HbA1c was 7.33% ± 1.49. DR signs were noted in 29.1% of patients and 0.89% of patients exhibited STDR. After establishing the diagnosis of STDR, treatment was initiated in 3.43 ± 1.98 months. CONCLUSION: Implementing the DR screening program provides valuable insights into managing diabetic retinopathy nationwide. It allows for the early detection of sight-threatening DR and facilitates timely and effective treatment, which could help prevent severe visual impairment.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Case Series and Systematic Review.

This study describes three unilateral cases of hemorrhagic occlusive retinal vasculitis (HORV) after cataract surgery and a review of the literature until February 2022, including 21 articles reporting HORV cases. Altogether, 61 eyes (41 patients) were included. Twenty patients had bilateral and 21 patients had unilateral HORV. Prophylactic vancomycin was given to all patients. Additional vancomycin use was associated with the worst outcome. The mean time to HORV was 9 days post-cataract surgery. In bilateral cases, the median time between surgeries was 7 days. Visual acuity was < 20/400 in 48%, with no light perception in 20%. Neovascular glaucoma developed in 43%. Central macular thickening or hyperreflectivity of the inner retinal layers on optical coherence tomography was associated with worse outcomes. Corticosteroid treatment, early panretinal laser photocoagulation, or anti-vascular endothelial growth factor therapy, and prophylaxis alternative to vancomycin is recommended. [Ophthalmic Surg Lasers Imaging Retina 2022;53:702-712.].

Changes in Plasma VEGF and PEDF Levels in Patients with Central Serous Chorioretinopathy.

Background and Objectives: Retinal pigment epitheliopathy and hyperpermeability of choroidal vessels were postulated to be involved in the pathogenesis of central serous chorioretinopathy (CSC). Imbalanced levels of vascular endothelial growth factor (VEGF) and pigment-epithelium-derived factor (PEDF) were previously implicated in the development of chorioretinal diseases characterized by increased vascular permeability. We aimed to compare the plasma levels of proangiogenic VEGF and antiangiogenic PEDF for 26 patients with acute CSC, 26 patients with chronic CSC, and 19 controls. Materials and Methods: VEGF and PEDF levels were measured using a multiplex immunoassay or enzyme-linked immunosorbent assay. Correlations with disease duration were assessed. Results: VEGF levels differed between groups (p = 0.001). They were lower in patients with acute CSC (p = 0.042) and chronic CSC (p = 0.018) than in controls. PEDF levels were similar in all groups. The VEGF-to-PEDF ratio was lower in CSC patients than in controls (p = 0.04). A negative correlation with disease duration was noted only for PEDF levels in the group with chronic CSC (rho = -0.46, p = 0.017). Discussion: Our study confirmed that patients with CSC have imbalanced levels of VEGF and PEDF. This finding may have important implications for the pathogenesis of CSC. VEGF-independent arteriogenesis rather than angiogenesis may underlie vascular abnormalities in these patients.

The GG genotype of erythropoietin rs1617640 polymorphism affects the risk of proliferative diabetic retinopathy in Slovenian subjects with type 2 diabetes mellitus: enemy or ally?

PURPOSE: The aim of this study was to investigate the relationship between erythropoietin rs1617640 polymorphism and proliferative diabetic retinopathy (PDR) in Slovenian subjects with type 2 diabetes mellitus. The second aim was to find whether erythropoietin expression in fibrovascular membranes varies among individuals carrying different genotypes of the rs1617640. METHODS: This was a retrospective cross-sectional study based on 797 unrelated Slovenian (Caucasian) participants with type 2 diabetes mellitus. The study group consisted of 217 cases with PDR and 580 controls without clinical signs of diabetic retinopathy. Each subject was genotyped for rs1617640 polymorphism. Fibrovascular membranes from 27 subjects who underwent vitreoretinal surgery were analysed with immunohistochemistry. We searched for expression of erythropoietin, its cognate receptor and for a pan-endothelial marker CD-34. RESULTS: Our results show that subjects carrying a minor GG genotype had significantly higher risk for PDR in both unadjusted (p = 0.02) and adjusted (p = 0.04) recessive genetic models. Subjects with the GG genotype had a 1.6-fold increased risk of developing PDR compared to subjects carrying the major T allele. In fibrovascular membranes from subjects with PDR, the mean number of cells expressing EPO was significantly higher in G allele carriers compared to the homozygotes for the common T allele. CONCLUSION: In Slovenian subjects with type 2 diabetes mellitus, a significant increased risk of PDR was found in GG carriers of the erythropoietin gene rs1617640 polymorphism.

Correlations between vitreous cytokine levels and inflammatory cells in fibrovascular membranes of patients with proliferative diabetic retinopathy.

Purpose: The purpose of this study was to investigate the levels of cytokines in the vitreous, and their correlation with the density of inflammatory cells in fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR) to evaluate intraocular inflammatory conditions with regard to disease activity. Methods: Thirty-three patients (33 eyes) with PDR requiring vitreoretinal surgery because of FVMs and tractional detachment were enrolled in the study, and compared with 20 patients (20 eyes) with macular hole (MH; control group). All patients underwent complete ophthalmological examinations before surgery. The activity of the disease was noted in patients with PDR. Samples of vitreous and blood were taken, and cytokine (MCP-1, IL-8, IL-6, VEGF, IL-1ß, TNF-α, MIP-1α, MIP-1ß, IL-10, and IL-12) levels were measured using cytometric bead array (CBA). Samples of FVMs were analyzed with immunohistochemical methods for the presence of inflammatory cells (CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells), and the numerical areal density was calculated (NA). Spearman's correlation was used to assess the association between variables. The Mann-Whitney test was used to assess the differences between independent groups. The Wilcoxon signed-rank test was used for assessing differences between two related groups. A p value of less than 0.05 was considered statistically significant. Results: Patients with active PDR had statistically significantly higher levels of MCP-1 (p = 0.003), VEGF (p = 0.009), and IL-8 (p = 0.02) in the vitreous in comparison with those with inactive PDR. CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells were identified in FVMs for patients with PDR. Statistically significantly higher numerical areal density of T lymphocytes (CD3+, CD4+, and CD8+) was demonstrated in patients with active PDR in comparison with patients with inactive PDR. Moderate to strong correlations were found between either MCP-1 or IL-8 in the vitreous, and the numerical areal density of cells (CD45+, CD3+, CD4+, and CD8+) in the FVMs, and weaker between either MCP-1 or IL-8 in the vitreous and the numerical areal density of CD14+ cells in the FVMs. Conclusions: The correlation of cytokine (MCP-1 and IL-8) vitreous levels with the density of inflammatory cells in FVMs, and differences in cytokine levels in the vitreous between patients with active and inactive PDR, and between the vitreous and serum in PDR indicate the importance of local intraocular inflammation in patients with PDR.

PREDICTING VISUAL OUTCOMES OF SECOND EYE VITRECTOMY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To investigate predictive factors for visual outcome in the second operated eye of patients undergoing bilateral vitrectomy for proliferative diabetic retinopathy. METHODS: Clinical records of 55 patients undergoing bilateral vitrectomy for proliferative diabetic retinopathy at the University Eye Hospital Ljubljana between January 2009 and December 2014 were examined retrospectively. Statistical analysis was performed to identify variables associated with good visual outcomes. RESULTS: Mean preoperative visual acuity was 6/181 Snellen (1.48 ± 0.47 logarithm of minimal angle of resolution [logMAR]). The follow-up period after vitrectomy was at least 1 year and mean postoperative visual acuity improved to 6/31 Snellen (0.71 ± 0.62 logMAR). On univariate analysis, variables predicting good postoperative vision (6/12 Snellen or better) were the following: absence of macular detachment (P = 0.009), previously performed full panretinal laser (P = 0.03), and good vision in the previously vitrectomized fellow eye (P < 0.001). On multivariate analysis, the absence of macular detachment (P = 0.001) and good vision in the previously vitrectomized fellow eye (P < 0.001) were both independently associated with good visual outcome. CONCLUSION: In patients undergoing second eye vitrectomy for complications of proliferative diabetic retinopathy, the visual acuity of previously operated fellow eye and the presence of macular detachment in the eye due for vitrectomy may be strong independent predicting factors for visual outcome.

Single nucleotide polymorphisms in the Trx2/TXNIP and TrxR2 genes of the mitochondrial thioredoxin antioxidant system and the risk of diabetic retinopathy in patients with Type 2 diabetes mellitus.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. The aim of this study was to examine the possible association between seven single nucleotide polymorphisms (SNPs) of the Trx2/TXNIP and TrxR2 genes encoding proteins involved in the thioredoxin antioxidant defence system and the risk of diabetic retinopthy (DR). DESIGN: Cross-sectional case-control study. PARTICIPANTS: A total of 802 Slovenian patients with Type 2 diabetes mellitus; 277 patients with DR and 525 with no DR were enrolled. METHODS: Patients genotypes of the SNPs; including rs8140110, rs7211, rs7212, rs4755, rs1548357, rs4485648 and rs5748469 were determined by the competitive allele specific PCR method. MAIN OUTCOME MEASURES: Each genotype of examined SNPs was regressed in a logistic model, assuming the co-dominant, dominant and the recessive models of inheritance with covariates of duration of diabetes, HbA1c, insulin therapy, total cholesterol and LDL cholesterol levels. RESULTS: In the present study, for the first time we identified an association between the rs4485648 polymorphism of the TrxR2 gene and DR in Caucasians with Type 2 DM. The estimated ORs of adjusted logistic regression models were found to be as follows: 4.4 for CT heterozygotes, 4.3 for TT homozygotes (co-dominant genetic model) and 4.4 for CT+TT genotypes (dominant genetic model). CONCLUSIONS: In our case-control study we were not able to demonstrate any association between rs8140110, rs7211, rs7212, rs4755, rs1548357, and rs5748469 and DR, however, our findings provide evidence that the rs4485648 polymorphism of the TrxR2 gene might exert an independent effect on the development of DR.

The rs6060566 of the reactive oxygen species modulator 1 (Romo-1) gene affects Romo-1 expression and the development of diabetic retinopathy in Caucasians with type 2 diabetes.

PURPOSE: The aim of this study was to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (Romo-1) gene in the development of diabetic retinopathy (DR) in Caucasians with type 2 diabetes (T2DM). Moreover, another aim was to investigate the effect of Romo-1 genotypes on Romo-1 expression in fibrovascular membranes from patients with proliferative DR. METHODS: A total of 806 subjects with T2DM were enrolled in cross-sectional case-control study: 278 patients with DR and 528 subjects without clinical signs of DR. Genetical analysis was performed in 806 subjects with T2DM. Moreover, immunohistochemical analysis of 40 fibrovascular membranes of patients with proliferative DR was performed. The number of positive (labelled) cells per area - numerical areal density of the Romo-1-positive cells (the number of positive cells/mm(2) ) - was calculated. RESULTS: A significantly higher frequency of the CC genotype of the rs6060566 polymorphism of the Romo-1 gene was found in subjects with T2DM with DR compared to those without DR (odds ratio=3.3, 95% confidence interval=1.1-8.8; p = 0.024). Moreover, the Romo-1 C allele was found to effect Romo-1 expression in fibrovascular membranes of patients with proliferative DR. CONCLUSIONS: The rs6060566 polymorphism of the Romo-1 gene was found to be an independent risk factor for DR in Caucasians with T2DM. Moreover, the rs6060566 is most probably functional and its effect might be mediated through the increased expression of Romo-1 in the retina.

GSTT1 null genotype is a risk factor for diabetic retinopathy in Caucasians with type 2 diabetes, whereas GSTM1 null genotype might confer protection against retinopathy.

AIM: Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy (DR). The aim of the present study was to investigate whether the genetic polymorphisms: polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 are associated with DR in Slovenian patients with type 2 diabetes. METHODS: In this cross sectional case-control study 604 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients with DR (cases) and the control group of 320 subjects with type 2 diabetes of more than 10 years' duration who had no clinical signs of DR. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: In our study, the deletion of the GSTM1 was found less frequent in cases with DR than in the controls (27.5% versus 44.4%; P < 0.001), whereas the deletion of GSTT1 was found significantly more often in cases than in the controls (49.3% versus 29.7%; P < 0.001). We did not find statistically significant differences in the genotype distribution in GSTP1 (Ile105Val) polymorphism between cases and controls (40.5% versus 46.0%). CONCLUSIONS: We may conclude that individuals homozygous for the deletion of GSTT1 are at an ≈ 2-fold-greater risk of DR, whereas the GSTM1 deficiency is associated with lower frequency of DR in type 2 diabetics.

A1/A2 polymorphism of the glycoprotein IIIa gene and diabetic retinopathy in Caucasians with type 2 diabetes.

BACKGROUND: A PlA1/A2 polymorphism of glycoprotein IIIa is known to be involved in the pathogenesis of arterial thrombosis, myocardial infarction, stroke and type 2 diabetes, but there is no evidence of association with diabetic retinopathy. The aim of this study was to examine the role of the PlA1/A2 polymorphism of the glycoprotein IIIa gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. DESIGN: Cross-sectional case-control study. PARTICIPANTS: Totally 222 patients with diabetic retinopathy and 120 diabetic subjects without clinical signs of diabetic retinopathy from the Eye Clinic, University Medical Centre Ljubljana were enrolled in the study. METHODS: Fundus examination and blood biochemical analysis were performed. The polymerase chain reaction and restriction fragment length polymorphism were used. MAIN OUTCOME MEASURES: The total cholesterol, triglyceride, high-density lipoprotein levels, fasting blood glucose and HbA(1c) were measured, and the genotypes of the PlA1/A2 polymorphism were determined. RESULTS: Patients with diabetic retinopathy had earlier onset, longer duration of type 2 diabetes and a higher incidence of insulin therapy compared to the diabetic patients without diabetic retinopathy. A significantly lower frequency of the A2A2 genotype of glycoprotein IIIa was found in diabetic patients with retinopathy compared to those without retinopathy (odds ratio = 0.49, 95% confidence interval = 0.28-0.89; P = 0.018). CONCLUSIONS: The A2A2 genotype of the glycoprotein IIIa polymorphism was associated with lower risk for diabetic retinopathy in Caucasians with type 2 diabetes. Further studies are needed to elucidate its protective role in the development of diabetic retinopathy in Caucasians.

Association of preoperative vitreous IL-8 and VEGF levels with visual acuity after vitrectomy in proliferative diabetic retinopathy.

PURPOSE: To determine whether the vitreous levels of interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) of patients with proliferative diabetic retinopathy (PDR) were associated with poor visual acuity after vitrectomy. METHODS: Observational cross-sectional study. Patient clinical characteristics and preoperative eye characteristics (63 eyes): visual acuity, iris neovascularization, vitreous haemorrhage, macular detachment, macular oedema, active retinal neovascularization, neovascularization of the disc, burned out PDR (defined as natural end stage of PDR with inactive membranes without previously performed laser photocoagulation) and panretinal photocoagulation were registered prior to vitrectomy for each patient. Vitreous VEGF and IL-8 levels were measured using the cytometric bead array method. Poor postoperative visual acuity was defined as visual acuity of <20/200 and was checked 2 years after vitrectomy. RESULTS: Twenty-one of the 63 eyes (33.3%) had poor visual acuity after vitrectomy. Univariate analysis showed that vitreous levels of IL-8, the absence of panretinal photocoagulation, preoperative macular detachment and poor preoperative visual acuity were significantly associated with poor final visual acuity after vitrectomy. A stepwise multiple logistic regression analysis showed that elevated vitreous levels of IL-8 (p < 0.0001), macular detachment (p = 0.011) and the absence of panretinal photocoagulation (p = 0.03) were independent predictors for poor visual outcome. CONCLUSIONS: Elevated vitreous IL-8 level could either be a marker of ischaemic inflammatory reaction, or it could play a role in deteriorating visual acuity by DR progression or both. Further studies are needed to provide better understanding of IL-8 and inflammation involvement in visual prognosis in PDR.

K469E polymorphism of the intracellular adhesion molecule 1 gene is associated with proliferative diabetic retinopathy in Caucasians with type 2 diabetes.

BACKGROUND: In proliferative diabetic retinopathy (PDR) increased levels of cytokines, inflammatory cells and angiogenic factors are present.These factors increase the expression of cellular adhesion molecules (CAMs)The objective of this study was to investigate the association between the polymorphisms of the ICAM-1 gene (K469E, G241A) and the development of PDR among patients with type 2 diabetes in the Slovenian population (Caucasians). METHODS: For the purpose, 195 subjects with type 2 diabetes with PDR were compared with 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. We analysed serum ICAM levels in 54 subjects with type 2 diabetes and 25 subjects without diabetes. RESULTS: A significantly higher frequency of the EE genotype of the K469E polymorphism of the ICAM-1 was found in the patients with PDR compared with those without diabetic retinopathy (OR = 2.0, 95% confidence interval [CI] = 1.1-3.5; P = 0.013), whereas the G241A polymorphism of the ICAM-1 gene failed to yield an association with PDR. Moreover, significantly higher sICAM-1 serum levels were demonstrated in diabetics with the EE genotype compared with those with the other (EK + KK) genotypes (918 +/-104 vs. 664 +/-209 microg/L; P = 0.001). The G241A polymorphism of the ICAM-1 gene, on the hand, failed to affect sICAM-1 serum levels in diabetics. CONCLUSIONS: We may conclude that the EE genotype of the K469E polymorphism of the ICAM-1 might be a risk factor for PDR in the Slovenian population (Caucasians) with type 2 diabetes.

Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy.

PURPOSE: In proliferative diabetic retinopathy (PDR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, growth factors, and angiogenic factors are present. Vascular endothelial growth factor (VEGF) appears to play a central role in mediating microvascular pathology in PDR. The purpose of the present study was to search for the association between the -634 C/G polymorphism of the VEGF gene and PDR. Moreover, it was hoped to determine whether serum and vitreous levels of VEGF are affected by genetic factors. METHODS: This cross-sectional case-control study enrolled 349 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus. The case group consisted of 206 patients with an advanced form of PDR and for whom vitrectomy was performed, and the control group had 143 patients who had no clinical signs of diabetic retinopathy but did have type 2 diabetes of more than 10 years duration. To analyze the genotype distribution we had to compare the genotype frequencies in diabetics with PDR (cases, n=206) and diabetics without diabetic retinopathy (control group, n=143). Additionally, to evaluate the effect of diabetes on the VEGF serum levels 2 groups, diabetics and non diabetics, were compared. First group were diabetics (diabetics with PDR, n=104), and second group were 29 subjects without diabetes. RESULTS: The -634 C/G VEGF polymorphism was not associated with PDR. Mean serum and vitreous levels of VEGF were statistically significantly higher in PDR in comparison to the control group. Moreover, significantly higher serum and vitreous levels of VEGF were demonstrated in diabetics with the CC genotype compared to those with the other (CG + GG) genotypes. CONCLUSIONS: VEGF is an important cytokine in PDR. Despite the effect of the -634 C/G VEGF polymorphism on serum and vitreous levels of VEGF in PDR, it failed to contribute to the genetic susceptibility to PDR.

Polymorphisms in the promoter region of the basic fibroblast growth factor gene and proliferative diabetic retinopathy in Caucasians with type 2 diabetes.

BACKGROUND: Basic fibroblast growth factor (bFGF) expression is implicated in proliferative diabetic retinopathy (PDR). The aim of this study was to investigate the association of genetic polymorphisms (-553T/A, -834T/A and -921C/G) in the promoter region of the bFGF gene with PDR in patients with type 2 diabetes. The second aim was to determine whether serum levels of bFGF are affected by genetic factors. METHODS: In this cross-sectional case-control study 313 unrelated Caucasians (Slovene population) with type 2 diabetes mellitus were enrolled: 206 patients with PDR and the control group of 107 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. We analysed serum bFGF levels in 78 subjects with type 2 diabetes and 25 subjects without diabetes. RESULTS: The AT genotype of the -553T/A polymorphism was present in 31 (15.0%) PDR patients and in seven (6.5%) controls (P = 0.03, odds ratio = 2.0, 95% confidence interval = 1.0-3.9). The AT genotype of the -834T/A polymorphism was present in 12 (5.8%) PDR patients and in 15 (14.0%) controls (P = 0.01, odds ratio = 0.4, 95% confidence interval = 0.2-0.8). Significantly higher bFGF serum levels were demonstrated in diabetics with the AT genotype of the -553 polymorphism compared with diabetics with the TT genotype, whereas the -834 and -921 polymorphisms failed to affect serum bFGF levels. CONCLUSIONS: We may conclude that the AT genotype of the 553 T/A polymorphism was associated with PDR in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of PDR in Caucasians, whereas carriage of the AT genotype of the -834 T/A polymorphism might decrease PDR risk.

Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients.

Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. In this cross sectional case-control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn-SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians.

Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy.

PURPOSE: To determine the levels of interleukin 8 (IL-8) in the vitreous of patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational case-control study. METHODS: Vitreous fluid samples were obtained by vitreoretinal surgery from 71 eyes of patients with diabetes mellitus type 2 with PDR and from 17 eyes of nondiabetic patients with a macular hole. PDR was classified as active and inactive and subdivided according to the extent of large-vessel gliotic obliteration. The cytokine levels were measured by cytometric bead array method. RESULTS: The vitreous levels of IL-8 were significantly higher in patients with PDR in comparison with the control subjects (P < .001) and in patients with higher extent of large vessel gliotic obliteration (P < .001). A vitreous level of IL-8 was not associated with the presence of active PDR. CONCLUSION: Increased levels of IL-8 in PDR were associated with a higher extent of large-vessel gliotic obliteration.

Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-gamma coactivator-1 gene might be a risk factor for diabetic retinopathy in Slovene population (Caucasians) with type 2 diabetes and the Pro12Ala polymorphism of the PPARgamma gene is not.

BACKGROUND: The peroxisome proliferator-activated receptor-gamma (PPARgamma) gene has been recently associated with type 2 diabetes, obesity and traits depending on VEGF expression (e.g. retinopathy). The PPARgamma gene and its coactivator, the peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) gene, have been implicated to be involved in glucose uptake and altered lipid oxidation. We therefore hypothesized that the Gly482Ser polymorphism of the PPARGC1 gene and Pro12Ala polymorphism of the PPARgamma gene might confer susceptibility to diabetic retinopathy in type 2 diabetes. The aim of this study was to investigate the association between the Pro12Ala polymorphism in the PPARgamma gene and Gly482Ser polymorphism in the PPARGC1 gene and the development of diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes. METHODS: One hundred and sixty subjects with type 2 diabetes and diabetic retinopathy were compared with 101 diabetic subjects without diabetic retinopathy. Chi-square test was used to compare discrete variables, and continuous clinical data were compared by unpaired students t - test. RESULTS: A significantly higher frequency of the AA genotype of the Gly482Ser polymorphism of the PPARGC1 gene was found in the patients with diabetic retinopathy compared to the patients without diabetic retinopathy (14.4% vs 5.9%; p = 0.035), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to yield an association with diabetic retinopathy. CONCLUSIONS: The present study demonstrates that the AA genotype of the Gly482Ser polymorphism in the PPARGC1 gene might be a risk factor for diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes (odds ratio 2.7, 95% confidence interval 1.0-6.8), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to confer susceptibility to diabetic retinopathy.