Automatic Detection of Microaneurysms in Fundus Images Using an Ensemble-Based Segmentation Method.

In this study, a novel method for automatic microaneurysm detection in color fundus images is presented. The proposed method is based on three main steps: (1) image breakdown to smaller image patches, (2) inference to segmentation models, and (3) reconstruction of the predicted segmentation map from output patches. The proposed segmentation method is based on an ensemble of three individual deep networks, such as U-Net, ResNet34-UNet and UNet++. The performance evaluation is based on the calculation of the Dice score and IoU values. The ensemble-based model achieved higher Dice score (0.95) and IoU (0.91) values compared to other network architectures. The proposed ensemble-based model demonstrates the high practical application potential for detection of early-stage diabetic retinopathy in color fundus images.

ABCA1 rs1883025 and CYP4F2 rs2108622 Gene Polymorphism Association with Age-Related Macular Degeneration and Anti-VEGF Treatment.

Background and Objectives: The age-related macular degeneration (AMD) pathophysiology is multifactorial, as it consists of interactions between aging, genetic, and environmental factors. We aimed to determine a relationship between AMD and the genes controlling lipid metabolism, and to assess its association with treatment results. The purpose was to find the ABCA1 rs1883025 and CYP4F2 rs2108622 gene polymorphisms in patients with exudative AMD (eAMD) treated with anti-VEGF. Materials and Methods: The study enroled 104 patients with eAMD and 201 healthy persons in a control group. The genotyping of rs1883025 and rs2108622 was performed using the RT-PCR method. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before anti-VEGF therapy, then at three and six months during the therapy, using optical coherence tomography (OCT). The patients were grouped to responders and non-responders according to the changes in BCVA and CRT. Results: The T allele at rs1883025 was more frequent in non-responder eAMD patients compared to responder eAMD patients (41.7% vs. 21.1%; p = 0.009). The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the eAMD group and the control group (56.35%, 39.78%, and 3.87% in the eAMD group and 53.33%, 39.05% and 7.62% in the control group, respectively, p = 0.286). The comparison of CRT and BCVA between the rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes (p = 0.030). Conclusion: The rs1883025 T allele was found to play a more significant role in non-responder eAMD patients compared to responder eAMD patients. The rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes.

RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.

OBJECTIVE: To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). DESIGN: Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study. PARTICIPANTS: Patients (N = 277) with visual impairment due to myopic CNV. METHODS: Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n=116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55). MAIN OUTCOME MEASURES: Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months. RESULTS: Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P<0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P<0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred. CONCLUSIONS: Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.

Associations of Tumor Necrosis Factor-Alpha Gene Polymorphisms (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-Alpha Serum Concentration with Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a neurodegenerative disease leading to irreversible central vision loss among the elderly in developed countries. While the disease accounts for 9% of all cases of vision loss, the prevalence of AMD is likely to increase due to the exponential aging of the population. Due to this reason, our study aimed to determine the associations of tumor necrosis factor-alpha (TNF-α) gene single-nucleotide polymorphisms (SNPs) TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-α serum concentration with age-related macular degeneration. Analysis of TNF-α rs1800630, rs1800629, and rs361525 polymorphisms showed that the TNF-α rs1800630 A allele was statistically significantly more frequent in the exudative AMD group compared to the control group (p = 0.029). Additionally, the TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in the control group of healthy females (p = 0.027). The TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in females with early AMD (p = 0.014). TNF-α rs1800630, rs1800629, and rs361525 haplotype A-A-G were associated with decreased odds of exudative AMD (p < 0.0001), and haplotype A-G-G was associated with 24-fold increased exudative AMD occurrence (p < 0.0001). TNF-α protein levels were lower in subjects with exudative AMD compared to the control group (p < 0.001). The study showed significant associations between inflammatory cytokine TNF-α single-nucleotide polymorphisms and serum level with AMD pathogenesis. Analysis of TNF-α genotypes and serum concentration may be helpful for the AMD diagnosis.

SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration.

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels.

Telomere Lengths and Serum Proteasome Concentrations in Patients with Type 1 Diabetes and Different Severities of Diabetic Retinopathy in Latvia and Lithuania.

The aim of the study was to compare telomere lengths and circulating proteasome concentrations in patients with different stages of diabetic retinopathy and type 1 diabetes in Latvia and Lithuania. Methods. Patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy were included in the NDR/NPDR group (n = 187). Patients with proliferative diabetic retinopathy and status post laser-photocoagulation were included int the PDR/LPC group (n = 119). Telomeres were evaluated by real-time quantitative polymerase chain reaction. Proteasome concentration was measured by ELISA. Results. Telomeres were longer in PDR/LPC (ΔCT 0.21 (0.12−0.28)) vs. NDR/NPDR (ΔCT 0.18 (0.1−0.28)), p = 0.036. In NDR/NPDR, telomeres were correlated negatively with age (R = −0.17, p = 0.019), BMI (R = −0.21, p = 0.004), waist/hip ratio (R = −0.21, p = 0.005), total cholesterol (R = −0.18, p = 0.021), and low-density cholesterol (R = −0.20, p = 0.010), and positively with estimated glomerular filtration rate (eGFR) (R = 0.28, p < 0.001). None of the above correlations were observed in PRD/LPC. Proteasome concentrations were lower in PDR/LPC (130 (90−210) ng/mL) vs. NDR/NPDR (150 (100−240) ng/mL), p = 0.024. This correlated negatively with eGFR (R = −0.17, p = 0.025) in the NDR/NPDR group and positively with age (R = 0.23, p = 0.014) and systolic blood pressure (R = 0.20, p = 0.032) in the PRD/LPC group. Telomere lengths did not correlate with proteasome concentrations. Conclusion. Longer telomeres and lower circulating proteasome concentrations are observed in patients with type 1 diabetes and advanced diabetic retinopathy.

Real-World Treatment Patterns and Vision Outcomes with Ranibizumab for Diabetic Macular Edema.

PURPOSE: To assess injection patterns and vision outcomes in patients receiving intravitreal ranibizumab injections for diabetic macular edema in a real-world clinical setting. METHODS: Retrospective chart review involving 74 eyes of 62 patients who started ranibizumab treatment for diabetic macular edema at the Hospital of the Lithuanian University of Health Sciences Kauno Klinikos. Data collected included follow-up visits, injections administered, and best-corrected visual acuity (BCVA). RESULTS: Median follow-up duration was 652.5 days (min 365; max 914). Over the first year, eyes received a median of 4 injections (min 1; max 10). Among eyes with 2-year follow-up and injections during the second year, there was a median of 3 injections (min 1; max 6) over the second year. The BCVA improved by a median of 5 letters 365 ± 60 days and 730 ± 60 days after baseline. At the first visit ≥365 days after baseline, 13.5% of eyes gained ≥15 letters from baseline while 6.8% of eyes lost ≥15 letters. For 74.3% of eyes, BCVA improved (gain of ≥5 letters) or remained stable (gain/loss of ≤4 letters). CONCLUSION: Intravitreal ranibizumab for diabetic macular edema was effective in a real-world clinical setting, with most eyes gaining or maintaining vision. Compared with randomized prospective clinical trials, patients received less frequent injections and achieved lower vision gains.

CYP4F2 (rs2108622) Gene Polymorphism Association with Age-Related Macular Degeneration.

Background. Age-related macular degeneration is the leading cause of blindness in elderly individuals where aetiology and pathophysiology of age-related macular degeneration are not absolutely clear. Purpose. To determine the frequency of the genotype of rs2108622 in patients with early and exudative age-related macular degeneration. Methods. The study enrolled 190 patients with early age-related macular degeneration, 181 patients with exudative age-related macular degeneration (eAMD), and a random sample of 210 subjects from the general population (control group). The genotyping of rs2108622 was carried out using the real-time polymerase chain reaction method. Results. The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the early AMD group, the eAMD group, and the control group. The CYP4F2 (1347C>T) T/T genotype was more frequent in males with eAMD compared to females (10.2% versus 0.8%; p = 0.0052); also T/T genotype was less frequently present in eAMD females compared to healthy control females (0.8% versus 6.2%; p = 0.027). Conclusion. Rs2108622 gene polymorphism had no predominant effect on the development of early AMD and eAMD. The T/T genotype was more frequent in males with eAMD compared to females and less frequently present in eAMD females compared to healthy females.

Photodynamic therapy and central serous chorioretinopathy.

Central serous chorioretinopathy is a common acquired maculopathy. Multiple studies showed that photodynamic therapy is useful treatment for acute and chronic central serous chorioretinopathy. The exact mechanism of photodynamic therapy in treating central serous chorioretinopathy is not clear, but it is thought to be caused by short-term choriocapillaris hypoperfusion and long-term choroidal vascular remodeling, leading to a reduction in choroidal congestion, vascular hyperpermeability and extravascular leakage. Furthermore, photodynamic therapy seems to be an effective means of improving or stabilizing visual acuity in patients with central serous chorioretinopathy.