PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion.

Association of PON1, APOE and SDF-1 Gene Polymorphisms with Treatment Response to Intravitreal Anti-VEGF Treatment in Patients with Retinal Vein Occlusion.

PURPOSE: The purpose of this study was to determine whether specific genetic polymorphisms affect the response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with macular oedema secondary to retinal vein occlusion (RVO). METHODS: Participants in this prospective study were 50 patients with macular oedema secondary to RVO, who were treated with intravitreal ranibizumab or aflibercept, and were followed-up for 12 months after initiation of treatment. Five single nucleotide polymorphisms (SNPs) from three different genes (APOE, PON1, SDF-1) were examined as potential predictors for treatment response to intravitreal anti-VEGF agents. RESULTS: Patients with the LL genotype of the PON1 L55M SNP had significantly higher reduction in central subfield thickness (CST) at month 12 after initiation of intravitreal anti-VEGF treatment (101.63 ± 56.80 µm in LL vs. 72.44 ± 39.41 µm in LM vs. 40.25 ± 19.33 µm in MM, p = .026). Patients with the M allele of the PON1 L55M SNP were significantly associated with lower reduction in CST compared to non-carriers (68.29 ± 38.77 µm in LM + MM vs. 101.63 ± 56.80 µm in LL, p = .032). CONCLUSION: PON1 L55M SNP may serve as a promising genetic biomarker for predicting response to intravitreal anti-VEGF treatment in patients with macular oedema due to RVO.

Bilateral Anterior Ischaemic Optic Neuropathy as First Manifestation of Henoch-Schönlein Purpura (IgA Vasculitis).

A 46-year-old man was referred to our department complaining of a bilateral progressive decrease in his visual acuity. Fundus examination revealed bilateral optic disc oedema, indicative of anterior ischaemic neuropathy (AION), and a macular star in the right eye. Laboratory analysis showed low haematocrit and haemoglobin, elevated creatinine, and increased erythrocyte segmentation rate and C-reactive protein level. Physical examination revealed the presence of purpuric rash on the trunk and the extremities. During the investigation we performed a complete laboratory and imaging examination for autoimmune collagen diseases, vasculitides and infectious diseases, which were all negative. Histologic findings of renal biopsy were compatible with IgA glomerulonephritis and thus Henoch-Schönlein purpura (HSP) diagnosis was established. The patient was treated with methylprednisolone and cyclophosphamide. Six months later, his renal function and his visual acuity had improved, and the rash had subsided. This is a rare case of AION in a patient with HSP.

Retinal neurodegeneration, macular circulation and morphology of the foveal avascular zone in diabetic patients: quantitative cross-sectional study using OCT-A.

PURPOSE: Using OCT-A to investigate the association between neurodegeneration and vascular morphology in diabetic retinopathy (DR). METHODS: Cross-sectional study. One hundred and sixty-two patients were enrolled and following fundoscopy were assigned to two groups according to DR severity: 54 patients to the group of no clinical signs of DR (noDR) and 54 to the non-proliferative DR (NPDR) group. Fifty-four age-matched patients without known diabetes were recruited as the control group. Patients underwent full ophthalmic examination followed by OCT-A. Central retinal thickness (CRT), vessel density (VD) in the superficial and deep retinal layers and foveal avascular zone (FAZ) area were measured. Additionally, ganglion cell complex (GCC) layer thickness along with global loss volume (GLV) and focal loss volume (FLV) indices was measured. RESULTS: In total, 85 men with mean age of 51.93 ± 9.03 and 77 women with age of 50.14 ± 10.35 were examined. Mean diabetes duration was 4.62 ± 2.16 years in the noDR group and 11.34 ± 2.73 years in the NPDR group (p < 0.001). Superficial VD (sVD) and deep VD (dVD) were significantly different only between noDR and NPDR groups (p < 0.001 for both comparisons), but no statistically significant difference was observed between the controls and the DR groups. Global loss volume was significantly higher in the NPDR (4.38 ± 2.22) compared to the noDR group (3.24 ± 1.76; p < 0.03). Focal loss volume was significantly higher in both noDR (1.22 ± 1.03) and NPDR (2.09 ± 1.72) groups compared to controls (0.95 ± 0.83; p < 0.001 between noDR and NPDR and p = 0.02 between control and noDR groups). Significant associations were found between GLV and deep VD (p < 0.01, r = -0.48), FLV and superficial VD (p < 0.01, r = -0.42) and FLV with deep VD (p < 0.01, r = -0.64). CONCLUSION: In this study, we evaluated the impact of DR in both the vascular layers and neural components of the retina as expressed by FAZ, sVD, dVD and GCC thickness, FLV and GLV using OCT-A. We found that FLV was significantly higher in both noDR and NPDR groups indicating that in progressive DR stages FLV values might be increased, which might serve as an early index of neuronal damage in patients with diabetes even in the absence of overt DR signs.

Vessel Density around Foveal Avascular Zone as a Potential Imaging Biomarker for Detecting Preclinical Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study.

Purpose: The purpose of this study was to investigate the changes of optical coherence tomography angiography (OCTA) parameters in diabetic retinopathy (DR) using an updated software with 3D projection artifact removal. Methods: In this cross-sectional observational study, 192 eyes of 111 patients with diabetes mellitus (DM) and 55 eyes of 34 age-matched healthy subjects were included. Diabetic patients were divided into three subgroups: without DR, with mild non-proliferative DR, and with moderate-to-severe non-proliferative DR. All eyes underwent dilated fundoscopy along with 3x3mm and 6x6mm OCTA image acquisition. Vessel density (VD), retinal thickness and foveal avascular zone (FAZ) parameters were analyzed. Correlation analyses between OCTA parameters and DR severity were also performed. Results: There was a statistically significant difference in all OCTA parameters among groups, except for superficial foveal VD in 6x6mm scan and whole image retinal thickness in both 3x3mm and 6x6mm scans, while 3x3mm scan parameters were found to be diagnostically superior to the corresponding ones of 6x6mm scan. As the DR stage progressed, the mean VD values decreased. FD-300, which is the VD of a 300-µm width annulus surrounding FAZ, demonstrated the strongest inverse correlation with DR severity (r = -0.590/rs = -0.562, p < .001) and showed the highest area under the ROC curve (AUROC = 0.833 ± 0.030, p < .001) in scan 3 × 3. Conclusion: OCTA shows progressive decrease of VD parameters with increasing DR severity. Foveal VD, FAZ area, and perimeter are not very useful indexes due to the high interindividual variability of FAZ size. OCTA and specifically FD-300 may serve as a promising DR screening tool for detecting preclinical microvascular alterations.