Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity.

BACKGROUND: To investigate the relationship between changes in circulating soluble CD40 ligand (sCD40L) levels and the presence and severity of type 2 diabetic retinopathy (DR). SUBJECTS AND METHODS: sCD40L plasma concentrations were measured in 205 type 2 diabetes (T2DM) patients without DR (DWR; n=50) and with DR (n=155), the latter subdivided into non-proliferative diabetic retinopathy [NPDR; n=98 (63.2%)], or proliferative retinopathy [PDR; n=57 (36.8%)] patients. RESULTS: Receiver operating characteristic analysis provided good discriminatory power for sCD40L as predictor of DR presence, with high sensitivity and specificity. Categorizing DWR and DR patients into sCD40L quartiles, based on sCD40L concentrations in T2DM without DR, demonstrated statistically significant gradual increase in DR risk with increasing sCD40L levels. sCD40L levels were significantly higher in DR compared to DWR patients. Plasma sCD40L levels differed significantly according to DR severity, and correlated with diabetes duration, dyslipedimea, nephropathy, and presence of DR, but not with gender, age, SBP, DBP, FPG, HbA1c, T2DM medications. Linear regression analysis confirmed the association of increased sCD40L levels with DR, independent of others parameters; mean plasma sCD40L levels differing significantly according to DR severity. CONCLUSION: Plasma sCD40L levels were positively associated with DR. The significant finding here is that sCD40L levels can be predictors of DR severity.

Anterior Chamber Angle, Volume, and Depth in a Normative Cohort-A Retrospective Cross-Sectional Study.

Purpose: The purpose of the study was to determine the distribution of the anterior chamber angle (ACA) within a population-based study sample in Germany and to find correlations between age, sphere, and biometric parameters of the anterior chamber. Patients and Methods: A total of 500 eyes, approximately 100 eyes per decade starting with patient age of 20 years, of 463 patients with an average age of 45.2 ± 14.1 (±values subsequent represent standard deviation) years without any known history of ocular diseases, surgery, or optic nerve head excavation or hypoplasia were included. ACAs, volume, and depth were correlated to age and sphere. Scheimpflug images (Pentacam, Oculus) with automatically measured ACAs were compared to manually measured angles (Bland Altman analysis) in this healthy population. Results: The mean manually measured ACA was 26.5° ± 3.9°; the highest average angle was found in the temporal position with 28.1° ± 4.9°, while the lowest average angle was found in nasal superior position with 25.7° ± 4.7°. Statistical analysis showed an average difference of +11.4° nasal and +12.1° temporal between the automatic measurements and the manually measured angles (P < 0.01). The analysis also revealed an independent inverted correlation between age (correlation coefficient between -0.28 and -0.38) and sphere (correlation coefficient between -0.44 and -0.51) of the participants and the anterior chamber volume, angle, and anterior chamber depth (P < 0.01 for all correlations). Conclusion: The ACA width manually measured is considerably less compared to automated imaging and formerly reported values. There is a significant difference in the ACA dependent on the position of measurement (superior, nasal, inferior, and temporal) with the average angle being inversely correlated to age and sphere. Abbreviations: AC: anterior chamber ACA: anterior chamber angle ACV: anterior chamber volume ACD: anterior chamber depth AAC: acute angle closure OAG: open-angle glaucoma OCT: optical coherence tomography ACG: angle-closure glaucoma MIGS: microinvasive glaucoma surgery PACS: primary angle-closure suspects.

Impact of lens densitometry on phacoemulsification parameters and usage of ultrasound energy in femtosecond laser-assisted lens surgery.

OBJECTIVE: The aim of this study was to find the correlation between lens densitometry measurements using Pentacam Scheimpflug imaging system with equivalent average ultrasound power and cumulative dissipated energy (CDE) in femtosecond laser-assisted lens surgery (FLALS). METHODS: One hundred and twenty-four eyes were analyzed retrospectively, of which 109 had undergone cataract surgery and 15 had received refractive lens exchange with FLALS. Using the Pentacam Nucleus Staging (PNS) lens densitometry program, preoperative mean lens density and cataract grading score were evaluated. Average ultrasound power and CDE were recorded during surgery and correlated with the PNS grading and average lens density value. Exclusion criteria included small pupil size, previous ocular surgeries, tumors, optic atrophy, corneal scarring, intraoperative capsular rupture, and zonular dehiscence. RESULTS: Preoperative average lens density compared with CDE showed a weak significant positive linear correlation (p < 0.0001). CDE increased as lens density increased. This was also noticed when CDE and ultrasound time were compared with the PNS grading, demonstrating a significant moderate correlation (p < 0.0001). With increasing average lens density, the equivalent average ultrasound power showed a positive correlation (p < 0.0001). A weak positive correlation between estimated fluid use and PNS was also observed (p < 0.0001). Forty-one cases that did not require ultrasound energy during phacoemulsification had a PNS score between 0 and 1. CONCLUSIONS: The Centurion Phacoemulsification machine has been shown to correlate positively with the Pentacam Scheimpflug System offering an objective and repeatable measure of lens density and cataract grading. This can aid in intraoperative phacodynamics and help reduce phacoemulsification complications, such as corneal endothelial injury.

Intraindividual comparative analysis of the visual performance after cataract surgery with implantation of a trifocal and a bifocal intraocular lens.

Presbyopia-treating intraocular lenses (IOLs) are now widely available and offer high predictability at all distances, better visual outcomes, and high patient satisfaction. In most patients, the same multifocal IOL is implanted bilaterally. In certain circumstances, such as during complex surgeries, it is important to be prepared with a backup plan to maintain surgical expectations. We report 3 patients who had femtosecond laser-assisted cataract surgeries in both eyes. The complicated eye had implantation of a bifocal IOL and the fellow eye of a trifocal IOL. This intraindividual analysis shows that combining a trifocal and a bifocal IOL can achieve high patient satisfaction and an overall good visual outcome.

Comparison of 2 laser fragmentation patterns used in femtosecond laser-assisted cataract surgery.

PURPOSE: To evaluate the effect of fragmentation patterns (pie pattern versus grid pattern) on effective phacoemulsification time (EPT). SETTING: Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany. DESIGN: Retrospective case series. METHODS: Eyes that had femtosecond laser-assisted cataract surgery were included. One half of the group was treated with the pie pattern. The preoperative lens density was evaluated by Scheimpflug imaging (Pentacam). Then, the eyes treated with the grid pattern were matched to the pie-pattern group based on lens density (Scheimpflug imaging). RESULTS: The study comprised 150 eyes (75 in the pie-pattern group and 75 in the grid pattern group). The mean patient age was 66 years ± 10.67 (SD). The Scheimpflug density zone was 10.05% ± 1.52%. The mean EPT was 6.63 ± 5.41 seconds for the pie pattern, significantly higher than the 4.26 ± 6.99 seconds for the grid pattern (P < .01, Wilcoxon rank-sum test). The number of eyes with EPT = 0 was significantly higher with grid pattern (37 for grid versus 1 for pie, P < .01, χ2 test). Regression analysis showed that the EPT was significantly dependent on lens density for both methods (P = .045 for pie versus P < .01 for grid). In eyes with a lens density higher than 12% (9 eyes in each group), the pie pattern showed significantly lower EPT (P = .02, Wilcoxon rank-sum test). CONCLUSIONS: In cases of low to moderate lens density, grid fragmentation pattern should be used because the EPT was significantly lower and a significantly higher number of eyes did not require further emulsification. However, in eyes with high density (>12%), pie-pattern fragmentation is recommended.

Effects of Atopic Syndrome on Keratoconus.

PURPOSE: To evaluate the effects of atopic syndrome on manifestations of keratoconus. METHODS: In this retrospective study, we reviewed patient files and data generated by Scheimpflug imaging of 670 eyes of 434 keratoconus patients. Patients were divided into a study group consisting of patients suffering from atopic syndrome (110 eyes of 75 patients), namely allergic asthma, atopic dermatitis, and/or allergic rhinitis, and a control group of patients without known atopic syndrome (560 eyes of 359 patients). RESULTS: We found a significant difference with the mean age being 36.1 ± 11.7 for the control group, 32.8 ± 9.6 for the atopic group (P = 0.002) with 1 atopic trait, and 30.4 ± 7.5 for patients with 2 or more atopic traits (P = 0.002). No statistically significant differences were found in the mean corrected distance visual acuity, corneal pachymetry, minimum relative pachymetric progression (RPImin), mean refraction, keratoconus index, anterior chamber depth and volume, Kmax, and location of Kmax in relation to the corneal apex. However, we found a significantly higher corneal density for the anterior 120 µm of the cornea in the atopic group (control: 20.74 ± 4.68, atopic group: 21.92 ± 4.65 P = 0.016). CONCLUSIONS: Keratoconus patients suffering from atopic syndrome were significantly younger but showed no topographical changes except in corneal densitometry compared with keratoconus patients without an atopic disease. This suggests atopic syndrome is a factor, which can trigger earlier manifestation of keratoconus.

Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor. Variability in VEGF expression, induced by specific VEGFA variants, are involved in angiogenesis-related disorders. This study examined the genotype distribution and functional role (VEGF expression) of rs699947, rs833061, rs1570360, rs2010963, rs833068, rs833070, rs3025020, and rs3025039 VEGFA variants and their haplotypes in 519 healthy Bahraini individuals of both genders. METHODS AND RESULTS: The distribution of the eight VEGFA polymorphisms screened was in Hardy-Weinberg equilibrium. The minor allele frequencies of rs699947 (0.42), rs833061 (0.32), rs1570360 (0.31), rs2010963 (0.33), rs833068 (0.37), rs833070 (0.42), rs3025020 (0.33), and rs3025039 (0.13) were generally compared to those established for Caucasians. Of the variants tested, rs3025020 was associated with increased VEGF serum levels (p=0.019), while rs3025039 was associated with decreased levels (p=0.038). Linkage analysis identified two VEGFA blocks, the first, spanning 16 kb, was not associated with altered VEGF levels, while the second, spanning 3 kb containing rs3025020 and rs3025039, was linked with higher VEGF expression, of which the (-583)T/(+936)T haplotype (p=0.008) was linked with higher VEGF levels compared to the (-583)C/(+936)C (all wild-type) haplotype. CONCLUSION: These results support the association of rs30250202 and rs3025039, and specific VEGF haplotypes, with altered VEGF serum levels, although the exact functional mechanisms remain to be elucidated.

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage.

OBJECTIVE: To evaluate the association of interleukin-18 (IL-18) promoter single-nucleotide polymorphisms rs1946519 (-656C/A), rs187238 (-137G/C), rs360718 (-119A/C), and rs360717 (-105G/A) and changes in IL-18 serum levels with recurrent spontaneous miscarriage (RSM). DESIGN: Case-control study. SETTING: Outpatient obstetrics and gynecology clinics. PATIENT(S): Women with confirmed RSM (n = 282), and 283 age- and ethnically matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IL-18 genotyping was accomplished by allelic discrimination assays; serum IL-18 levels were measured by ELISA. RESULT(S): The minor allele frequencies of rs360717 and rs1946519, but not rs360718 or rs187238, were higher in patients with RSM. Significant differences in the distribution of the rs360717 and rs1946519 genotypes were noted between patients and controls, and both rs360717 and rs1946519 IL-18 single-nucleotide polymorphisms showed significant association with RSM under additive, dominant, and recessive models. Lower serum IL-18 levels were seen between patients and controls and were more pronounced in rs360717 and rs1946519 heterozygous and homozygous genotypes. Four-locus (rs1946519/rs187238/rs360718/rs360717) IL-18 haplotype analysis identified that the AGAA (Pc<.001), CGAA (Pc<.001), and ACAG (Pc=.018) haplotypes were associated with a reduction in IL-18 secretion and with increased RSM risk, after adjustments for body mass index, menarche, and gravida. CONCLUSION(S): These results demonstrated that reduced IL-18 levels and rs360717 and rs1946519 IL-18 variants are significantly associated with RSM.

Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage.

OBJECTIVES: Insofar as recurrent spontaneous miscarriage (RSM) is linked with dysregulated immunity and inflammatory changes, and given the pro-inflammatory role of interleukin-21 (IL-21), we examined the association between IL-21 polymorphisms and RSM. METHODS AND RESULTS: IL-21 rs2055979, rs13143866, rs9992580, and rs4833837 were genotyped in 235 cases of RSM and 235 controls. Regression analysis was employed in assessing the contribution of IL-21 variants to the overall RSM risk. Higher minor allele and genotype frequencies of rs2055979 and rs13143866, but not rs9992580 or rs4833837, were seen in RSM patients than in the controls. IL-21 haplotype [rs9992580/rs4833837/rs2055979/rs13143866] analysis revealed a lower frequency of the TGCG haplotype, and a higher frequency of the GGCG and GAAA haplotypes in patients, thus conferring protection from or a susceptibility to RSM by these haplotypes respectively. Regression analysis confirmed the association of TGCG [OR (95%CI)=0.09 (0.05-0.16)], and GGCG [OR (95%CI)=2.52 (1.34-4.54)] and GAAA [OR (95%CI)=4.02 (2.20-7.70)] haplotypes, after adjusting for age and BMI. CONCLUSIONS: Our findings indicate that IL-21 is a novel susceptibility gene for RSM.

Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage.

The association of vascular endothelial growth factor (VEGF) -583C/T variant with recurrent miscarriage (RSM) was investigated in 173 RSM cases and 248 control women. Increased minor allele and genotype frequencies of -583C/T, and reduced serum VEGF concentrations were associated with increased risk of RSM.

Anti-annexin V IgM and IgG autoantibodies and the risk of idiopathic recurrent spontaneous miscarriage.

Anti-annexin V antibodies have been identified as risk factors for recurrent spontaneous miscarriage (RSM) in some, but not all previous studies. We investigated the association between anti-annexin IgM and IgG in RSM cases and control women. Blood samples from 244 women with idiopathic RSM, and 283 multi-parous control women were tested for anti-annexin V antibodies by ELISA. A significant elevation in anti-annexin V IgM and IgG was seen in the RSM cases. An increased prevalence of elevated anti-annexin V IgM and to a lesser extent anti-annexin V IgG was seen in RSM patients. Receiver operating characteristic analysis indicated that the area under the curve for anti-annexin V IgM was 0.916, and for anti-annexin V IgG was 0.725. A systematic shift in anti-annexin V IgM and IgG distributions toward higher values occurred in RSM women, which was confirmed by percentile analysis. For each of the anti-annexin V isotypes, the adjusted odds ratio increased as the percentile value increased; the strongest risk was for anti-annexin V IgM, in which the 99th percentile (P99) was associated with a 165-fold higher risk than P50, and for anti-annexin V IgG where P99 was associated with a 38-fold higher risk than P50. In addition, a higher prevalence of elevated anti-annexin V IgM and anti-annexin V IgG was seen in RSM cases than in control women. We conclude that anti-annexin V IgM and IgG antibody positivity are independent risk factors for RSM.

Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study.

BACKGROUND: Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D). METHODS: We examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. RESULTS: Enrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls. CONCLUSIONS: CAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.