Janus Kinase Inhibitors: Next-Generation Treatment for Uveitis. / Januskinase-Inhibitoren: Next-Generation-Therapie der Uveitis.

A large proportion of patients with visual impairment secondary to non-infectious uveitis may require DMARDs. Although these are highly effective, some patients may require alternatives to the currently available immunomodulators due to an inadequate response or undesirable side effects. Janus Kinase Inhibitors (JAKi) are already approved for several autoimmune diseases in rheumatology, gastroenterology and dermatology. To date, JAKi have been studied in phase 3 trials in various types of uveitis. Mechanism of Action: JAKi work by inhibiting the phosphorylation of Janus kinases, which are transmembrane proteins. This blocks the activation of transcription factors, which in turn downregulates cytokine expression and inflammatory mediators. JAKi represent an extremely effective novel therapeutic approach in rheumatology, gastroenterology and dermatology. They have already been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and atopic eczema. In earlier comparative studies with conventional biologics, a better therapeutic response was reported in some cases. Several published case reports report reduced cortisone levels in patients with uveitis who had responded poorly to conventional and biological DMARDs. Approval studies are under way for JIA-associated and ANA-positive anterior uveitis. In summary, JAKi represent an innovative treatment option for patients with non-infectious uveitis in whom DMARDs are contraindicated or ineffective.

Ocular toxicity due to Trametinib and Dabrafenib.

BACKGROUND: To report a case of uveitis and neuroretinal detachment in a patient treated with Trametinib and Dabrafenib due to metastatic cutaneous melanoma stage IV. CASE PRESENTATION: We evaluated slit lamp examination, fundoscopy, optical coherence tomography, fluorescein and indocyanine green angiography in a 66 years old man suffering visual loss. Fundoscopy showed serous neuroretinal detachment of the fovea accompanied with white spots surrounding the fovea in both eyes. Although therapy with Trametinib and Dabrafenib was stopped uveitis anterior was seen 2 weeks later. After a year, the therapy was started again and the serous neuroretinal detachment appeared once more, however without inflammatory reaction of the anterior chamber. CONCLUSION: Patients treated with Trametinib and Dabrafenib should undergo consecutive eye examinations from the beginning of the therapy.

Analysis of functional polymorphisms in apoptosis-related genes in primary open angle glaucoma.

PURPOSE: Glaucoma is a disease with high heritability in which the degradation of retinal ganglion cells occurs via apoptosis. Therefore, we investigated the role of four functional apoptosis-related gene variants (Akt1 rs1130233, Bax rs4645878, Fas rs223476, and FasL rs763110) in patients with primary open angle glaucoma. METHODS: 334 patients with primary open angle glaucoma and 334 controls were recruited for this case-control study. The main outcome measures were genotype distribution and allelic frequencies determined with PCR. RESULTS: After adjustment for multiple testing, no significant difference in either the genotype distribution or the allelic frequencies of any investigated gene variant was found. CONCLUSIONS: Our findings indicate that the investigated gene polymorphisms are unlikely to be major risk factors for primary open angle glaucoma in Caucasian patients.

Use of true net power in intraocular lens power calculations in eyes with prior myopic laser refractive surgery.

Intraocular lens (IOL) power calculation following laser refractive surgery is still one of the most challenging aspects in cataract surgery. This study was initiated to investigate the application of true net power (TNP; Pentacam, software version 6.02r10, Oculus, Germany) in IOL power calculations in eyes with prior laser refractive surgery. Our data contribute to the notion that the TNP of the Pentacam is a reliable alternative to determine the IOL power in cases where the historical data are missing. Based on our data, we recommend implementing the TNP to obtain the true corneal power and thus, reliable IOL power calculations.

Analysis of Choriocapillaris Reperfusion Topography following Faricimab Treatment for Neovascular Age-Related Macular Degeneration in Non-Treatment-Naïve Patients.

To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in age-related macular degeneration (AMD) when transitioning from various anti-VEGF treatments to faricimab, using optical coherence tomography angiography (OCTA). 25 eyes of 22 individuals who underwent intravitreal faricimab injections for neovascular AMD with type 1 MNV were included. OCTA images were obtained prior to (T0), after one (T1), and after three faricimab injections (T2); Noteworthy changes occurred in the first ring at T2 in comparison to T0. The percentage of CC flow deficit (FD%), FD average area (FDa), and FD number (FDn) in 5 rings (R1-R5) surrounding the dark halo around the MNV were calculated. A reduction in FD% at T2 compared to T0 (50.5 ± 10.2% at T0, 46.4 ± 10.6% at T2; p = 0.020) was seen, indicating CC reperfusion. Additionally, we observed a reduction in the average FDa (140.2 ± 172.1% at T0, 93.7 ± 101.8% at T2; p = 0.029). Our study highlights an FD% after three consecutive faricimab injections. The most pronounced effect was observed in the first ring, directly adjacent to the dark halo, suggesting a partial CC reperfusion surrounding the MNV, potentially indicating disease regression.

Cataract-1K Dataset for Deep-Learning-Assisted Analysis of Cataract Surgery Videos.

In recent years, the landscape of computer-assisted interventions and post-operative surgical video analysis has been dramatically reshaped by deep-learning techniques, resulting in significant advancements in surgeons' skills, operation room management, and overall surgical outcomes. However, the progression of deep-learning-powered surgical technologies is profoundly reliant on large-scale datasets and annotations. In particular, surgical scene understanding and phase recognition stand as pivotal pillars within the realm of computer-assisted surgery and post-operative assessment of cataract surgery videos. In this context, we present the largest cataract surgery video dataset that addresses diverse requisites for constructing computerized surgical workflow analysis and detecting post-operative irregularities in cataract surgery. We validate the quality of annotations by benchmarking the performance of several state-of-the-art neural network architectures for phase recognition and surgical scene segmentation. Besides, we initiate the research on domain adaptation for instrument segmentation in cataract surgery by evaluating cross-domain instrument segmentation performance in cataract surgery videos. The dataset and annotations are publicly available in Synapse.

Analysis of Choriocapillaris Reperfusion Topography Following Faricimab Treatment for Neovascular Age-Related Macular Degeneration in Therapy-Naïve Patients.

INTRODUCTION: To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in treatment-naïve age-related macular degeneration (AMD) after faricimab application using optical coherence tomography angiography (OCTA). METHODS: Twenty-five eyes of 25 treatment-naïve individuals who underwent intravitreal faricimab injections for neovascular AMD (nAMD) with type 1 MNV were included. Spectral-domain optical coherence tomography (SD-OCT) images and en-face swept-source OCTA images were analyzed, and the percentage of CC flow deficit (FD%), FD average area (FDa) and FD number (FDn) in five progressive 20.0-µm-wide concentric rings (R1, R2, R3, R4 and R5) surrounding the dark halo around the MNV were calculated. Image acquisition was carried out prior to the first faricimab injection (T0) and 1 month after the injection (T1). RESULTS: The topographical sub-analysis revealed noteworthy changes in all rings at T1 compared to T0. There was a notable progressive reduction in FD% at T1 compared to T0 values across all rings, indicating a gradual CC reperfusion following anti-VEGF treatment. Additionally, the average size of FD decreased after the loading phase. Although not reaching statistical significance, there was a progressive reduction in the FDa across all rings. CONCLUSION: Our study highlights a CC FD reduction following the administration of three consecutive faricimab injections. This effect was detected in all rings surrounding the dark halo. These observations suggest a partial CC reperfusion surrounding the MNV, potentially serving as an indicator for disease regression.

Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration.

PURPOSE: Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. DESIGN: Prospective cohort study. PARTICIPANTS: We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. METHODS: All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. MAIN OUTCOME MEASURES: Mean change in visual acuity at the end of the treatment period. RESULTS: The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. CONCLUSIONS: The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

[Combined transepithelial PTK and topography-guided PRK for treatment of trauma-related corneal scarring]. / Kombinierte transepitheliale PTK und topografiegesteuerte PRK zur Behandlung von traumatisch bedingten Hornhautnarben.

BACKGROUND: Corneal scars can severely impair visual performance and treatment can be challenging. The study aimed to evaluate a promising minimally invasive option in the treatment of corneal scars using transepithelial topography-guided ablation. METHODS: This retrospective interventional study involved four eyes of four patients who developed corneal scarring and irregular surfaces due to trauma and were treated with topography-guided photorefractive keratectomy (TG-PRK) between 2017 and 2020. The ablation profile was calculated in all four cases using CRS-Master (Zeiss, Jena, Germany). The main outcome measures were uncorrected and best-corrected distance visual acuity, manifest refraction and corneal regularity by topographic images. The mean age was 34.75 ± 15.39 years and the follow-up time was 6 months for all patients. RESULTS: In three cases full subjective refraction was corrected in one session and one patient had a refractive error of +0.5 D. Only corneal surface smoothing without additional refractive correction was performed in this case. All four patients showed improvement in uncorrected (2-3 Snellen lines) and corrected (3 Snellen lines) distance visual acuity. No complications occurred during or after the treatment and there was no reduction of visual acuity in any case. CONCLUSION: The use of TG-PRK in patients with corneal scarring improves visual acuity in selected cases. In myopic patients most of the refractive error can also be corrected in a single session.

Effects of Type 2 Diabetes Mellitus and Smoking on Changes in Corneal Endothelial Morphology and Cell Density.

PURPOSE: The purpose of this study was to compare the corneal endothelial morphology and cell density of diabetic smokers and nonsmokers with 50 to 70 age-matched healthy subjects and to determine whether smoking increases the effects of type 2 diabetes mellitus (DM) on these corneal parameters. METHODS: This prospective cohort study included 200 patients who were assigned to 4 groups, including smokers with type 2 DM (group 1), nonsmokers with type 2 DM (group 2), healthy smokers (group 3), and healthy nonsmokers (control group, group 4). Noncontact specular microscopy was used to measure central endothelial cell density (ECD), coefficient of variation of cell area, percentage of hexagonal cells, and central corneal pachymetry (CCT). RESULTS: According to the ECD and CCT values ( P < 0.001 and P = 0.013, respectively), a significant difference was observed between the groups. The mean ECD was lowest in diabetic smokers (1917 ± 399 cells/mm 2 ). Healthy smokers and diabetic smokers had significantly lower ECD compared with the control group ( P = 0.03 and P < 0.001, respectively). Healthy smokers and diabetic smokers had significantly lower ECD compared with diabetic nonsmokers ( P = 0.012 and P < 0.001, respectively). The cornea was significantly thicker in the diabetic smokers than in the control group ( P = 0.013). CONCLUSIONS: The coexistence of DM and smoking causes a significant decrease in ECD and an increase in CCT. Cigarette smoking is more harmful to corneal endothelial cells than DM alone.

Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.

PURPOSE: The enzyme cholesterol 24S-hydroxylase (Cyp46A1) is responsible for the conversion of cholesterol to its more polar metabolite 24S-hydroxycholesterol, thereby enabling the intracerebral elimination of cholesterol. An intronic single nucleotide polymorphism in the gene CYP46A1 (IVS2 -150 T>C; rs754203) has recently been associated with primary open angle glaucoma (POAG). This association, however, lacks confirmation in other studies. The purpose of the present study was to investigate a hypothesized association between rs754203 and the presence of POAG in a Central European population of Caucasian descent. METHODS: The present institutional study comprised a total of 581 unrelated subjects: 330 patients with POAG, and 251 control subjects. Main outcome measures are genotype distributions and allelic frequencies determined by polymerase chain reaction. RESULTS: No significant differences in either genotype distribution or allelic frequencies were found between patients with POAG and control subjects (p>0.05). The presence of the rs754203 T-allele was associated with a nonsignificant odds ratio of 0.81 (95% CI: 0.63-1.04; p=0.11) for POAG. CONCLUSIONS: Our data suggest that the rs754203 polymorphism itself is unlikely a genetic risk factor for POAG in Caucasian individuals.

Role of inflammation-related gene polymorphisms in patients with central retinal vein occlusion.

OBJECTIVE: Central retinal vein occlusion (CRVO) is a vision-threatening disease, primarily occurring among patients aged more than 60 years. Several risk factors, including arterial hypertension and diabetes mellitus, have been identified. Compression of the central retinal vein by an atherosclerotic retinal artery at the lamina cribrosa also has been implicated in the pathogenesis of the disease. Functional gene polymorphisms of cytokines or chemokines previously shown to affect atherogenesis or hemostasis are potential risk factors for CRVO. The present study investigates a hypothesized association between inflammation-related gene polymorphisms and the presence of CRVO in a relatively large cohort of patients. DESIGN: Case-control study. PARTICIPANTS: The study group consisted of 315 patients with CRVO and 335 control subjects. METHODS: Determination of genotypes was done by 5' exonuclease assay (TaqMan). MAIN OUTCOME MEASURES: Genotypes of interleukin (IL)1ß -511C>T, IL1 receptor antagonist (IL1RN) 1018T>C, IL4 -584C>T, IL6 -174G>C, IL10 -592C>A, IL18 183A>G, tumor necrosis factor (TNF)-α -308G>A, monocyte chemoattractant protein (MCP)-1/CCL2 -2518A>G, IL8 -251A>T, and RANTES (CCL5) -403G>A polymorphisms. RESULTS: Genotype distributions and allele frequencies of the investigated gene polymorphisms did not significantly differ between both groups (P>0.05). Arterial hypertension, diabetes mellitus, and cigarette smoking were significantly more frequent in patients with CRVO than among control subjects (arterial hypertension: 67.0% vs. 52.2%, P<0.001; diabetes mellitus: 16.8% vs. 6.3%, P<0.001, cigarette smoking: 32.1% vs. 23.6%, P = 0.02). In a logistic regression analysis, the presence of arterial hypertension was associated with an odds ratio (OR) of 1.75 (95% confidence interval [CI], 1.26-2.44) in those with CRVO, whereas an OR of 2.52 (95% CI, 1.46-4.35) was found in those with diabetes mellitus. A history of cigarette smoking was associated with an OR of 1.57 (95% CI, 1.09 - 2.25) for CRVO. CONCLUSIONS: Our data suggest that the investigated inflammation-related gene polymorphisms are unlikely major risk factors for CRVO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Automatic detection of pupil reactions in cataract surgery videos.

In the light of an increased use of premium intraocular lenses (IOL), such as EDOF IOLs, multifocal IOLs or toric IOLs even minor intraoperative complications such as decentrations or an IOL tilt, will hamper the visual performance of these IOLs. Thus, the post-operative analysis of cataract surgeries to detect even minor intraoperative deviations that might explain a lack of a post-operative success becomes more and more important. Up-to-now surgical videos are evaluated by just looking at a very limited number of intraoperative data sets, or as done in studies evaluating the pupil changes that occur during surgeries, in a small number intraoperative picture only. A continuous measurement of pupil changes over the whole surgery, that would achieve clinically more relevant data, has not yet been described. Therefore, the automatic retrieval of such events may be a great support for a post-operative analysis. This would be especially true if large data files could be evaluated automatically. In this work, we automatically detect pupil reactions in cataract surgery videos. We employ a Mask R-CNN architecture as a segmentation algorithm to segment the pupil and iris with pixel-based accuracy and then track their sizes across the entire video. We can detect pupil reactions with a harmonic mean (H) of Recall, Precision, and Ground Truth Coverage Rate (GTCR) of 60.9% and average prediction length (PL) of 18.93 seconds. However, we consider the best configuration for practical use the one with the H value of 59.4% and PL of 10.2 seconds, which is much shorter. We further investigate the generalization ability of this method on a slightly different dataset without retraining the model. In this evaluation, we achieve the H value of 49.3% with the PL of 18.15 seconds.

Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in open angle glaucomas.

PURPOSE: Matrix metalloproteinases (MMPs) play an essential role in the turnover of the extracellular matrix and cellular behavior. MMP1, MMP2, and MMP9 have previously been implicated in the pathogenesis of primary open angle glaucoma (POAG) and open angle glaucoma secondary to exfoliation syndrome (XFG), respectively. Functional gene polymorphisms of these MMPs such as MMP1 -1607 1G/2G (rs1799750), MMP2 -1306 C/T (rs243865), MMP2 -1575 G/A (rs243866), and MMP9 Q279R (rs17576) are thus plausible candidates as risk factors for open angle glaucomas. The purpose of the present study was to investigate hypothesized associations between these polymorphisms and the presence of POAG and XFG in a Caucasian population. METHODS: The present case-control study included 322 patients with POAG, 202 patients with XFG, and 248 control subjects. Genotyping of polymorphisms was done using polymerase chain reaction. RESULTS: No significant differences in either genotype distributions or allelic frequencies of MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R were found between patients with POAG and control subjects and patients with XFG and control subjects, respectively (p>0.05). The presence of POAG or XFG was not predicted by any of the investigated polymorphisms. CONCLUSIONS: Our data suggest that the MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R polymorphisms themselves are unlikely major risk factors among Caucasian patients with either POAG or XFG.

Choroidal Infiltration as First Clinical Manifestation of T-cell Large Granular Lymphocyte (T-LGL) Leukemia.

Purpose: To report of a 55-year-old woman suffering from choroidal infiltrates as a first clinical manifestation of T-LGL leukemia. Methods: Retrospective case report. Results: A healthy woman presented with photophobia in both eyes since 1 month. She showed a panuveitis with anterior chamber as well as vitreous cells, creamy-white choroidal lesions in both eyes and a cystoid macular edema in the left eye. Lab testing showed only a moderate lymphocytosis, all other tests, including a pars plana vitrectomy and an anterior chamber tap, were negative. Due to the persistent lymphocytosis, she was referred to the oncologist. A biopsy of the bone marrow revealed T-LGL leukemia. A subsequent biopsy of the choroid showed an infiltration of T-LGL and therefore systemic therapy with cyclophosphamide was started. Conclusions: This is a very rare case describing an involvement of the choroid in T-LGL leukemia.

Analysis of three pigment epithelium-derived factor gene polymorphisms in patients with exudative age-related macular degeneration.

PURPOSE: Exudative age-related macular degeneration (exudative AMD) is a common vision-threatening disease, with both environmental and genetic factors contributing to its development. Recently, homozygosity for the 72Met variant of the pigment epithelium-derived factor (PEDF) Met72Thr gene polymorphism (rs1136287) was identified as a novel risk factor for exudative AMD in Chinese patients from Taiwan. The role of this polymorphism, however, has not yet been determined in a white European population. In addition, two other PEDF gene polymorphisms, -5736T>C (rs12150053) and -5304C>T (rs12948385), have been associated with increased risk of diabetic retinopathy, but have not yet been studied among patients with exudative AMD. The purpose of the present study was thus to investigate a hypothesized association between these PEDF polymorphisms and the presence of exudative AMD in a white European population. METHODS: The present case-control study comprised 269 patients with exudative AMD and 155 control subjects. Genotypes of the PEDF polymorphisms were determined by 5'-exonuclease assays (TaqMan). RESULTS: PEDF genotype and allele frequencies were not significantly different between AMD patients and control subjects. The two promoter polymorphisms, -5736T>C (rs12150053) and -5304C>T (rs12948385), were in complete association. Presence of the homozygous PEDF 72 Met/Met genotype was associated with a nonsignificant odds ratio of 1.00 (95% confidence interval: 0.67-1.49, p=0.99). Similarly, presence of the homozygous PEDF -5736 TT genotype or -5304 CC genotype was associated with a nonsignificant odds ratio of 0.99 (95% confidence interval: 0.56 - 1.75, p=0.97). Both promoter polymorphisms were in linkage disequilibrium with the Met72Thr (rs1136287) polymorphism (D'=0.83) and formed three common and one rare haplotype. Haplotype frequencies were similar between AMD patients and control subjects (p>0.05). CONCLUSIONS: Our data suggest that none of the investigated PEDF polymorphisms is likely a major risk factor for exudative AMD in a white European population.

TNF-alpha -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.

PURPOSE: TNF-alpha has been suggested to participate in the pathogenesis of exfoliation glaucoma (XFG). The purpose of the present study was to investigate a hypothesized association between two common functional polymorphisms in the promoter region of the TNF-alpha gene (TNF-alpha -308 G>A, rs1800629, and TNF-alpha -238 G>A, rs361525) and the presence of XFG in a Caucasian population. METHODS: The present case-control study comprised 408 participants (204 patients with XFG and 204 control subjects). Control subjects were matched for age and sex. Genotypes of the TNF-alpha -308 G>A and TNF-alpha -238 G>A polymorphisms were determined by polymerase chain reaction (restriction fragment length polymorphism). RESULTS: No significant differences regarding genotype distribution or allelic frequencies were found between patients and control subjects (p>0.025). The presence of the TNF-alpha -308 G-allele was associated with an insignificant odds ratio of 0.98 (95% confidence interval [CI]: 0.66-1.46; p=0.99) while the presence of the TNF-alpha -238 G-allele was associated with an insignificant odds ratio of 0.64 (95% CI: 0.33-1.23; p=0.25). CONCLUSIONS: Our data suggest that both the TNF-alpha -308 G>A and the TNF-alpha -238 G>A polymorphisms are unlikely to be major risk factors for XFG in an European population of Caucasian descent.

Analysis of inflammation- and atherosclerosis-related gene polymorphisms in branch retinal vein occlusion.

PURPOSE: Branch retinal vein occlusion (BRVO) is a common vision-threatening disease. Compression of the underlying retinal vein due to increased rigidity of the crossing artery has been implicated in the pathogenesis of BRVO. Among others, arterial hypertension and hypercholesterolemia, both of which contribute to atherogenesis, have been identified as risk factors. Atherosclerosis itself is a chronic low-grade inflammatory disease with a distinct pro-inflammatory cytokine pattern. In addition to their role in atherogenesis, some cytokines have been shown to exert procoagulatory effects, and may thus contribute to the development of BRVO by a second mechanism. Gene polymorphisms affecting the expression of inflammation-related cytokines are therefore candidates as potential risk factors for BRVO. The purpose of the present study was to investigate hypothesized associations between cytokine gene polymorphisms and the presence of BRVO. METHODS: The study comprised 398 patients with BRVO and 355 control subjects. Using 5'exonuclease assays (TaqMan), genotypes of the following functional single nucleotide polymorphisms were determined: interleukin 1 beta (IL1B) -511C>T, interleukin 1 receptor antagonist (IL1RN) 1018T>C, interleukin 4 (IL4) -584C>T, interleukin 6 (IL6) -174G>C, interleukin 8 (IL8) -251A>T, interleukin 10 (IL10) -592C>A, interleukin 18 (IL18) 183A>G, tumor necrosis factor (TNF) -308G>A, monocyte chemoattractant protein 1 (CCL2) -2518A>G, and RANTES (CCL5) -403G>A. RESULTS: Neither genotype distributions nor allele frequencies of any of the investigated polymorphisms differed significantly between BRVO patients and controls (p>0.05). Arterial hypertension was found to be significantly more prevalent in BRVO patients than in controls (p<0.001). In a logistic regression analysis presence of arterial hypertension was associated with an odds ratio of 3.33 (95% confidence interval: 2.42-4.57) for BRVO. CONCLUSIONS: As none of the investigated gene variants was significantly more prevalent in BRVO patients than among control subjects, our data suggest that these polymorphisms themselves are unlikely major risk factors for BRVO.

Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Among other cytokines, interleukin 22 (IL-22) has been implicated in the pathogenesis of chronic plaque psoriasis. The purpose of this study was to investigate a hypothesized association between common IL-22 gene polymorphisms and chronic plaque psoriasis. METHODS: Genotypes of 10 common polymorphisms of the IL-22 gene were determined by fluorogenic 5' exonuclease assays (TaqMan) in 475 patients with chronic plaque psoriasis and 252 controls. RESULTS: Two blocks of high linkage disequilibrium, formed by eight polymorphisms upstream of exon 5 (rs2227485, rs2227491, rs2046068, rs1179251, rs1012356, rs2227501, rs2227503, rs976748) and two polymorphisms in the 3' near gene region (rs1182844, rs1179246), were observed within the IL-22 gene. Neither single polymorphisms nor haplotypes were significantly associated with the presence or clinical features of chronic plaque psoriasis (P > 0.05). CONCLUSIONS: Our data suggest that the investigated IL-22 gene polymorphisms are unlikely major risk factors for chronic plaque psoriasis.

Multiplex bead analysis of vitreous and serum concentrations of inflammatory and proangiogenic factors in diabetic patients.

PURPOSE: To investigate the role of inflammatory and angiogenic factors in the pathogenesis of diabetic retinopathy, we determined, in diabetic patients and controls, vitreous and serum concentrations of interferon-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated upon activation, normal T-expressed and secreted (RANTES), and vascular endothelial growth factor (VEGF). METHODS: We recruited 36 probands with type 2 diabetes mellitus (15 noninsulin-dependent and 21 insulin-dependent) and 69 normal controls. Using Cytometric Bead Array Technology, we measured vitreous and serum concentrations of IP-10, MCP-1, MIP-1alpha, MIP-1beta, RANTES, and VEGF. RESULTS: In diabetic patients the mean vitreous levels of IP-10, MCP-1 and VEGF were significantly higher compared normal controls. [IP-10 (pg/mL) 254.84 +/-311.67 versus 78.90 +/- 67.94 (p<0.001); MCP-1 (pg/mL) 1127.14 +/- 738.91 versus 700.80 +/-419.21 (p=0.002); VEGF (pg/mL) 954.98 +/- 2315.09 versus 37.90 +/- 28.51(p<0.001)]. Vitreous levels of VEGF correlated with vitreous levels of both IP-10 and MCP-1 (p<0.05). MIP-1beta, RANTES, and VEGF mean serum levels were significantly raised in diabetic probands while IP-10, MCP-1, and MIP-1alpha serum levels showed no significant elevation compared to controls [IP-10 (pg/mL) 346.20 +/- 287.36 versus 328.74 +/-352.35 (p=0.88); MCP-1(pg/mL) 133.10 +/- 89.10 versus 141.47 +/- 222.15 (p=0.50); MIP-1beta (pg/mL) 184.40 +/- 100.20 versus 139.56 +/- 151.38 (p=0.003); RANTES (pg/mL) 51336.23 +/- 19940.31 versus 33629.2 +/- 33301.0 (p=0.002); VEGF (pg/mL) 304.88 +/- 257.52 versus 154.45 +/- 114.78 (p<0.001)]. CONCLUSIONS: Our results suggest that in diabetics, there is an upregulation of IP-10, MCP-1, and VEGF in the vitreous and an upregulation of MIP-1beta, RANTES, and VEGF in the serum. These findings support the concept of an angiogenic and inflammatory element in the development of diabetic retinopathy.