Three-year clinical outcome of XEN45 Gel Stent implantation versus trabeculectomy in patients with open angle glaucoma.

OBJECTIVE: To reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma. SUBJECT/METHODS: We conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.e., IOP ≤ 18 mmHg, ≥20% IOP reduction and not requiring IOP-lowering medication) up to 36 months postoperatively. RESULTS: Between 2013 and 2019, we performed XEN Gel Stent implantation in 58 eyes and trabeculectomy in 84 eyes. From baseline to 36 months, mean IOP decreased from 23.4 to 13.8 mmHg (mean reduction 35%, 95% confidence interval 23-48%, p < 0.001) in the XEN group and from 25.1 to 11.2 mmHg (mean reduction 50%, 41-60%, p < 0.001) in the TRAB group. TRAB provided higher IOP reduction than XEN Gel Stent implantation at 12, 24, and 36 months (all p < 0.05). In XEN versus TRAB, IOP-lowering medication was required by 98.3% vs. 97.6% before surgery (p = 0.781), differed significantly at month 12 (43.2% vs. 2.0%, p < 0.001)but not at month 24 or 36. Complete surgical success was achieved in 40.0% vs. 62.8% at month 24 (adjusted odds ratio 2.70; 1.04-7.00, p = 0.040) and 27.3% vs. 56.8% at month 36 (4.36; 1.25-15.18, p = 0.021). CONCLUSION: Compared to XEN, TRAB was associated with lower intraocular pressure, less IOP-lowering medication, and higher probability of achieving complete surgical success over a 36-month follow-up period.

Eye Disease in Patients with Rheumatic Diseases: A Retrospective Observational Cohort Study.

Data on eye diseases in rheumatic patients are limited. The aim of this study was to retrospectively assess the prevalence of ophthalmologic diseases in patients at a rheumatology outpatient clinic who also visited the ophthalmologic clinic. For this retrospective observational cohort study, a chart review was performed according to the STROBE guidelines. In this cohort, an ophthalmologic diagnosis was made in 26.9% of the 1529 rheumatic outpatients, whereas from a rheumatologic perspective, inflammatory non-infectious diagnoses dominated, at 71.7%. From an ophthalmologic perspective, diagnoses without inflammatory pathophysiologic backgrounds dominated, at 54.9%. Inflammatory non-infectious ophthalmologic disease was diagnosed in 24.2% of patients with rheumatoid arthritis and 29.3% of patients with peripheral spondyloarthritis. Not a single rheumatoid arthritis patient was diagnosed with anterior uveitis; however, 16.5% of spondyloarthritis patients were diagnosed with anterior uveitis (p < 0.001). The prevalence of uveitis was 16.3% in axial and 20.1% in peripheral spondyloarthritis. In conclusion, an interdisciplinary rheumatologic-ophthalmologic setting appears justified to further improve the management of patients with rheumatic diseases.

Maculopathies in Glaucoma. / Glaukomassoziierte Makulopathien.

In the presence of glaucoma, various changes in the macula can occur during the course of the disease itself or its treatment. Maculopathies that can be observed in glaucoma include cystoid macular edema, hypotony maculopathy, and microcystic macular edema. The following article discusses the pathophysiology, causes, course, clinical presentation, and treatment of these maculopathies.

Intermittent retinal artery occlusions as the first clinical manifestation of polycythemia vera: a case report.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm with increased hemoglobin, hematocrit, platelet count and leukocytosis, resulting in increased blood viscosity. PV which is initially presenting with ocular symptoms is rare, but irreversible retinal vessel occlusions leading to the diagnosis of PV have been described in literature. CASE PRESENTATION: We describe a patient with PV, initially presenting with attacks of monocular temporary loss of vision due to intermittent retinal artery occlusions of different retinal arteries. The patient was immediately treated with phlebotomy and the impaired arterial retinal perfusion could be restored without permanent retinal ischemia. We were able to document these transient arterial occlusions with fundus photography as well as fluorescein angiography. To the best of our knowledge, a case like this has never been documented before. CONCLUSION: This report is pertinent, in order to raise awareness among clinicians for polycythemia vera, as it can in fact be used as a differential diagnosis for patients with retinal artery occlusion. We would like to stress that early therapy might reverse the vessel complications.

Symptomatic idiopathic bilateral multifocal retinal pigment epithelial detachments.

PURPOSE: To report a rare case of idiopathic bilateral serous retinal pigment epithelial detachments. OBSERVATIONS: We present a case of a 43-year-old female patient with metamorphopsia with the presence of innumerable bilateral serous retinal pigment epithelial detachments. Detailed ocular and systemic clinical work-up revealed no underlying disease. CONCLUSIONS: /Importance: Idiopathic multiple serous retinal pigment epithelial detachments are an extremely rare condition, that has been observed as an incidental clinical finding in asymptomatic patients. Multimodal imaging and detailed systemic work up are essential to rule out an underlying disease. Initial symptoms, as in our case, are uncommon and usually occur only in patients with complications such as choroidal neovascularization or hemorrhages. Therefore, regular follow ups are recommended to early detect and treat possible complications.

Uveitis in Tumor Patients Treated with Immunological Checkpoint- and Signal Transduction Pathway-Inhibitors.

PURPOSE: New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. METHODS: In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. RESULTS: Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. CONCLUSIONS: Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment.

Effects of glaucoma surgery on visual field progression in open-angle glaucoma considering the floor effect.

PURPOSE: The aim of this retrospective analysis was to investigate whether trabeculectomy (TRAB) and XEN® Gel Stent implantation (XEN) - both filtrating surgery techniques - can slow down the deterioration of visual field (VF) parameters considering the floor effect, which could lead to a misestimation of pre- and postoperative VF rate of progression (ROP). METHODS: Included in this study were patients with open-angle glaucoma, who underwent either TRAB or XEN® gel stent implantation and who had at least three VF tests before and after surgery, over an observation period of 13 years. The annual ROP of the mean defect (MD) and the square root of loss variance (sLV) were calculated with two different censoring thresholds: by censored regression and by ordinary least squares regression (OLSR). In addition, the diagnostic range of sLV was calculated. RESULTS: 48 eyes of 39 glaucoma patients were included in the study. The annual rate of MD progression was significantly reduced by filtering surgery when calculating the yearly ROP using OLSR (p = 0.006) and by censoring values exceeding a precalculated cut-off of 14.20 dB (p = 0.041) and a cut-off from the literature of 15.00 dB (p = 0.028). On average, the MD was impacted by a significant floor effect of 14.20 dB (95% CI: 12.83-15.56), corresponding to 17.7/59 absolute defects or 29.9% of the whole VF. When applying both OLSR and censored regression, the annual rate of sLV progression did not show a significant difference. The sLV showed a diagnostic boundary at a MD of 15.78 dB. CONCLUSION: This study shows that filtering surgery can reduce the progression of VF in patients with open-angle glaucoma, especially those whose disease develops aggressively. This is valid even if the floor effect in advanced cases is compensated by censored regression. On average, the ROP of MD is affected by a significant floor effect at about 29.9% absolute loss of the whole VF.

Two-year outcomes of minimally invasive XEN Gel Stent implantation in primary open-angle and pseudoexfoliation glaucoma.

PURPOSE: The aim of this study was to evaluate the efficacy of XEN® Gel Stent implantation in the treatment of primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (XFG) regarding the reduction of intraocular pressure (IOP) and number of IOP-lowering medications over 2 years. METHODS: In this retrospective, observational, single-centre study, patients with POAG or XFG underwent implantation of the XEN® Gel Stent with or without combined phacoemulsification. Changes in mean IOP, mean number of IOP-lowering medications, number of postoperative interventions, complete or qualified surgical success rate (defined as IOP < 18 mmHg without or with IOP-lowering medication, respectively) and complete surgical failure rate (defined as the necessity of a glaucoma-related secondary surgical intervention or loss of light perception) were assessed 12 months (12M) and 24 months (24M) postoperatively. RESULTS: Seventy-nine eyes of 63 patients with open-angle glaucoma were included in the study (71% POAG, 29% XFG). Before surgery, mean IOP was 23.4 ± 7.9 mmHg. IOP was 14.6 ± 3.6 mmHg 12 months postoperatively (-31% from baseline, 95% CI -42% to -20%, n = 30, p < 0.001) and 14.8 ± 4.4 mmHg 24 months postoperatively (-29% from baseline, 95% CI -30% to -41%, n = 28, p < 0.001). Mean number of IOP-lowering medications was significantly reduced from 2.7 ± 1.1 before surgery to 1.0 ± 1.2 (-69%, 95% CI -89% to 46%, p < 0.001) 12 months after surgery and 1.0 ± 1.2 (-64%, 95% CI -91% to -36%, p < 0.001) at 24 months after surgery. Complete surgical success was achieved in 39% (12M) and 34% (24M) of patients and qualified success in 29% (12M) and 27% (24M). 13 (16%) eyes were classified as complete surgical failure. In 62% of the patients needling procedures had to be performed. CONCLUSION: The XEN® Gel Stent is an efficacious minimal invasive glaucoma surgery for primary open-angle and pseudoexfoliation glaucoma, resulting in significant reduction of IOP and a reduction in glaucoma medications from baseline in two-third of treated patients with 2-year follow-up. Frequent follow-up examinations were mandatory to identify early and late bleb failure and additional needling procedures were necessary to reestablish aqueous flow.

Susac syndrome (Retino-cochleo-cerebral vasculitis), the ophthalmologist in the role of the whistleblower.

BACKGROUND/PURPOSE: Susac syndrome is a rare microangiopathy of suspected autoimmune origin affecting arteries of the retina, the cochlea and the brain. The aim of the study was to give a review of the disease entity and determine the proportion of cases and their characteristics in a uveitis referral centre. PATIENTS AND METHODS: Charts of patients with the diagnosis of Susac syndrome seen in the Uveitis Clinic of the Centre for Ophthalmic Specialised Care (COS), Lausanne, Switzerland were reviewed retrospectively to determine the frequency of such cases in a uveitis referral centre. Clinical symptoms and signs, functional data, imaging signs and evolution were analysed in the 3 COS cases and one case shared with the Uveitis Clinic of the Department of Ophthalmology, University of Innsbruck, Austria. Characteristic signs were searched possibly allowing a prompt diagnosis. RESULTS: During the period from 1994 to 2019 (24 years, 2045 patients), 3 charts with the diagnosis of Susac syndrome were found (0.15%). The whole collective, including the additional case, comprised three women aged 28, 32 and 63 at presentation and one man, aged 42. None of the 3 cases that were referred were diagnosed beforehand. The characteristic item found in all 4 cases was the abrupt arterial stop or segmental interruption of arteries and increased staining of arterial wall on angiography more clearly shown on indocyanine green angiography that can potentially be proposed as a crucial diagnostic element. All 4 cases responded to dual steroidal and non-steroidal immunosuppression. Under treatment, all four patients did not show any further evolution. CONCLUSION: Susac syndrome is a multilocation arteritis of the head that can involve the eye, ear and brain often first diagnosed by the ophthalmologist. The diagnosis is rapidly reached in uveitis referral centres but seems to be missed otherwise, A helpful angiographic sign to be searched is an abrupt or segmental arterial stop and increased staining of the arterial wall more clearly seen on indocyanine green angiography. Patients often present first to the ophthalmologist who should be acting as a whistleblower to avoid severe involvement of the brain.

Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis.

BACKGROUND: Serum neurofilament light chain (sNfL) levels and peripapillary retinal nerve fiber layer (pRNFL) are both emerging biomarkers of neuro-axonal damage in multiple sclerosis (MS). However, data on the relation between sNfL and pRNFL are scarce. OBJECTIVE: We aimed to determine the relation of sNfL levels with pRNFL thinning in a large cohort of relapsing-remitting (RR) MS patients. METHODS: We identified 80 patients from a prospective, 3-year observational study on retinal changes in RRMS with annual blood samples available. sNfL levels were measured using single-molecule array (SimoaTM) assay. Annualized loss of pRNFL (aLpRNFL) was determined by individual linear regression models. Correlations between single and repeated sNfL levels and aLpRNFL were analyzed using multivariate linear regression and mixed-effect models. RESULTS: After correction for sex, age, and baseline sNfL, an sNfL increase of 10 pg/mL was associated with an aLpRNFL of -0.7 µm (95% confidence interval (CI): (-1.3, -0.2), p < 0.001). Patients with ⩾2 sNfL measurements >75th percentile displayed higher aLpRNFL (2.2 µm, standard deviation (SD) 0.6) compared to patients with no sNfL measure >75th percentile (0.4 µm, SD 0.2, p < 0.001). Between 15% and 20% of the aLpRNFL variance could be predicted from sNfL levels. CONCLUSION: sNfL levels contribute to the prediction of retinal thinning in patients with RRMS, strengthening its value as a biomarker of neuro-axonal damage.

Smelling multiple sclerosis: Different qualities of olfactory function reflect either inflammatory activity or neurodegeneration.

BACKGROUND: Peripapillary retinal nerve fiber layer (pRNFL) thickness and olfactory function are both emerging biomarkers in multiple sclerosis (MS). Impairment of odor identification and discrimination is an irreversible feature of more advanced MS suggested to be associated with neurodegeneration, while olfactory threshold is a transient feature of early, active MS possibly associated with short-term inflammatory disease activity. OBJECTIVE: The aim of this study was to validate the association of olfactory (dys)function and parameters of MS disease course in a large cohort of MS patients and to correlate olfactory function with pRNFL thickness as a surrogate biomarker of neurodegeneration. METHODS: In a cross-sectional design, olfactory function was assessed using the Sniffin' Sticks test, which quantifies three different qualities of olfactory function (threshold, discrimination, and identification). pRNFL thickness was measured by spectral-domain optical coherence tomography (OCT). Results were correlated with age, sex, disease duration, relapses, Expanded Disability Status Scale (EDSS), cognitive function, depression, smoking, and pRNFL thickness by multivariable linear regression models. RESULTS: We included 260 MS patients (mean age of 35.9 years, 68.7% female). Olfactory threshold correlated significantly with number of relapses in the year prior to assessment and shorter disease duration. Odor discrimination, identification, and their sum score were significantly correlated with longer disease duration, higher EDSS, and reduced cognitive function. pRNFL thickness was associated with identification and discrimination, but not with threshold. CONCLUSION: Olfactory threshold is a marker of short-term inflammatory relapse activity unrelated to parameters of neurodegeneration, while odor identification and discrimination are markers of neurodegeneration mostly independent of relapse activity. Assessment of olfactory function provides an opportunity to stratify MS patients with regard to inflammation and neurodegeneration.

N-chlorotaurine Inactivates Acanthamoeba and Candida albicans in the Porcine Ex Vivo Corneal Infection Model.

PURPOSE: N-chlorotaurine (NCT) is an anti-infective belonging to the class of chloramines and an investigative drug for the topical treatment of keratoconjunctivitis. The aim of the present study was to demonstrate its efficacy against Acanthamoeba and Candida in corneas infected ex vivo. METHODS: Corneal buttons from porcine eyes were contaminated with Acanthamoeba castellanii trophozoites or Candida albicans Centraalbureau voor Schimmelcultures 5982 and incubated for 7 and 3 days, respectively. Subsequently, they were treated with 1% NCT for 5 to 120 minutes. After further incubation for 2 days in the absence of NCT in tests with A. castellanii, the buttons were homogenized, and the amoebae grown for a further 5 days before they were counted in a light microscope. For C. albicans, quantitative cultures were performed from corneal homogenates. RESULTS: Incubation of 120 minutes in NCT completely inhibited the regrowth of A. castellanii and reduced the number of C. albicans colony-forming unit counts by 4 log10. In addition, at 60 minutes, significant reductions of both pathogens could be observed. Histology showed penetration of pathogens into the stroma of the corneal buttons. CONCLUSIONS: NCT inactivates A. castellanii and C. albicans in corneal tissue.

Peripapillary retinal nerve fibre layer as measured by optical coherence tomography is a prognostic biomarker not only for physical but also for cognitive disability progression in multiple sclerosis.

BACKGROUND: Peripapillary retinal nerve fibre layer (pRNFL) thickness is emerging as a marker of axonal degeneration in multiple sclerosis (MS). OBJECTIVE: We aimed to prospectively assess the predictive value of pRNFL for progression of physical and cognitive disability in relapsing-remitting MS (RRMS). METHODS: In this 3-year longitudinal study on 151 RRMS patients, pRNFL was measured by spectral-domain optical coherence tomography (OCT). We used proportional hazard models, correcting for age, sex, disease duration, Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) at baseline, to test a pRNFL thickness ≤88 µm at baseline for prediction of EDSS progression and cognitive decline. We also evaluated the decrease in pRNFL thickness from baseline to year 3 in a multivariate linear regression model. RESULTS: pRNFL thickness ≤88 µm was independently associated with a threefold increased risk of EDSS progression ( p < 0.001) and a 2.7-fold increased risk of cognitive decline within the subsequent 3 years ( p < 0.001). Mean pRNFL delta was -5.3 µm (SD, 4.2). It was significantly negatively impacted by EDSS progression, cognitive decline, higher age and disease duration, while positively impacted by disease-modifying therapy (DMT). CONCLUSION: Cross-sectional and longitudinal monitoring of pRNFL is useful as a biomarker for prediction of physical and cognitive disability progression in patients with RRMS in everyday clinical practice.

Differential clinical presentation of Adamantiades-Behçet's disease in non-endemic and endemic areas: retrospective data from a Middle-European cohort study.

OBJECTIVES: To assess demographical and clinical data in a Middle-European cohort of patients with Adamantiades-Behçet's disease (ABD), together with the use of medication in adherence to international guidelines. METHODS: In a retrospective cohort study, in- and outpatients of an Austrian secondary and tertiary university hospital center were analyzed independent from the medical discipline involved. After ethics approval, screening for ABD-patients in the clinical information system resulted in 1821 documents from 1997 to 2016. Patients fulfilling the International Criteria for Behçet's Disease were included, and ABD symptoms and signs together with medical interventions for immunosuppression, anticoagulation and pain management were identified by individual chart reviews and evaluated for conformity with international recommendations. RESULTS: A total of 76 ABD patients were identified with 39.1% Austrian and 37.0% Turkish origin. Genital aphthae and skin manifestations were more frequent, neurological, gastrointestinal and vascular manifestations less frequent in ABD patients of Turkish origin living in Austria compared to those living in Turkey (each P < 0.05). The male-to-female ratio averaged 0.86 (0.39 in patients with Austrian and 1.43 with Turkish backgrounds), and was 3.3 in patients with venous manifestations. Out of 174 medical interventions, 55.2% fully matched the European League Against Rheumatism recommendations of 2008, and 93.7% were considered at least as equal to the recommendations. Indications for tumor necrosis factor inhibition were in line with the 2007 Sfikakis recommendations. CONCLUSIONS: In this Middle-European ABD cohort clinical presentations between patients of Austrian and Turkish origin do not strongly vary, whereas Turkish patients from the non-endemic Innsbruck cohort present differently compared to patients living in Turkey. The role of such cohort analyses will increase, from the epidemiological as well as the management perspective.

Severe reactive ischemic posterior segment inflammation in Acanthamoeba keratitis: Case report of a patient with Sjögren's syndrome.

PURPOSE: We report on a case of Acanthamoeba keratitis (AK)-related reactive ischemic posterior segment inflammation following intraocular surgery in a patient with primary Sjögren's syndrome (PSS). CASE REPORT: A 48-year-old female patient with severe protracted AK underwent uneventful cataract surgery upon development of a corneal scar. Four weeks postoperatively, she experienced a rapid loss of vision to no light perception. Central retinal artery occlusion and ischemic optic neuropathy could be excluded, and a diagnosis of PSS was made. The condition remained unresponsive to systemic steroid treatment and ultimately led to enucleation of the globe. Histologic work-up revealed ischemic posterior segment inflammation and Acanthamoeba cysts in the corneal stroma. CONCLUSION: Autoimmune disease may be a risk factor for AK-related severe reactive ischemic posterior segment inflammation, and intraocular surgery can be a trigger to its manifestation.

Susac's syndrome: clinical course and epidemiology in a Central European population.

OBJECTIVE: Susac's syndrome is characterized by inflammation and occlusion of pre-capillary arterioles with the clinical triad of branch retinal artery occlusion (BRAO), encephalopathy and hearing loss. No epidemiological data are available for the disease. METHODS: All neurology departments in Austria were addressed to report adult patients who were on immunosuppressive treatment for a diagnosis of Susac's syndrome between 1 August 2010 and 1 August 2015. Clinical course, treatment regimens, period and point prevalence rates, and annual incidence of Susac's syndrome in Austria in people over 19 years of age are reported. RESULTS: Ten patients with Susac's syndrome were identified, and eight of them were newly diagnosed within the five-year timeframe. Minimum five-year period prevalence of the disease is 0.148/100,000 (95% confidence interval (CI) 0.071-0.272), annual incidence is 0.024/100,000 (95% CI 0.010-0.047). Minimum point prevalence rates varied from 0.030/100,000 (95% CI 0.004-0.108) to 0.088/100,000 (95% CI 0.032-0.192). Of all 10 patients, 8 showed typical callosal or internal capsule magnetic resonance imaging lesions at first presentation, 7 presented with BRAO and 5 had hearing loss or tinnitus at the beginning of the disease. Four patients developed the complete clinical triad of Susac's syndrome during the observation period. CONCLUSIONS: We provide for the first time population-based data about the clinical course, prevalence and incidence of Susac's syndrome.

Microbial contamination of glaucoma eyedrops used by patients compared with ocular medications used in the hospital.

The aim of this study was to compare the percentage of contamination of multiuse eyedrops applied by glaucoma patients at home and by the medical personnel at the outpatient department, the ward, and the operating room of our Department of Ophthalmology. Eyedrops were collected over a period of 11 months. Samples were taken from the dropper tip (smear), drops, and the residual fluid inside the bottle and cultivated on blood agar. Colony forming units were counted and identified by mass spectrometry. The percentage of contamination was significantly higher in eyedrops applied by the patients (29/119; 24.4%, P < 0.01), used in the ward (26/133; 19.5%, P < 0.01), and in the outpatient unit (6/35; 17.1%, P = 0.036) compared with that in the operating room (6/113; 5.3%). The median period of use was 1 week in the operating room compared with 4 weeks in the other groups (P < 0.01). Glaucoma medications were significantly more frequently contaminated than antibiotic and anesthetic eyedrops (P < 0.05). For eyedrops applied by the patients, the tip was more frequently contaminated than the drops and the residual internal fluid. For eyedrops from the ward, the opposite was true. Pathogenic strains (Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter lwoffii, Stenotrophomonas maltophilia, and Staphylococcus aureus) were found only in 6 bottles (1.5%), whereas most of the detected microbes belonged to human or environmental flora. This study underlines the importance of hygienic handling of eyedrops and raises the question of whether single-use glaucoma medication might be preferred to reduce the risk of contamination.

N-chlorotaurine and its analogues N,N-dichloro-2,2-dimethyltaurine and N-monochloro-2,2-dimethyltaurine are safe and effective bactericidal agents in ex vivo corneal infection models.

PURPOSE: N-chlorotaurine (NCT) and its analogues N-monochloro-2,2-dimethyltaurine (NVC-612) and N-dichloro-2,2-dimethyltaurine (NVC-422) are new anti-infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo. METHODS: Corneal buttons were excised from porcine eyes. In 183 of the 229 corneas, erosion and artificial superficial stromal incision were induced. They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus aureus for 24 hr at 37°C and incubated in solutions of the test substances at 37°C and pH 7.1. Subsequently, they were subjected to histology (n = 20) or homogenized followed by quantitative bacterial cultures (n = 209). Ocular irritation was tested using the EpiOcular™ tissue system (MatTek Corporation). RESULTS: Bacterial accumulations were detected histologically both on the corneal surface and also in the anterior third of the stroma of incised corneal buttons. All three test compounds at a concentration of 55 mm (equals 1% NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately 5 log10 after 60- and 120-min incubation, respectively. Significant killing was observed as early as after 5-min incubation. Also intrastromal bacteria were inactivated. In the EpiOcular™ tissue model, NCT, NVC-422 and NVC-612 had no or very low potential to irritate corneal tissue. CONCLUSION: N-chlorotaurine, NVC-422 and NVC-612 are non-irritating in cornea and kill P. aeruginosa and S. aureus, even following penetration into the deeper corneal stromal layers.

No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients.

PURPOSE: Substantial evidence suggests that ocular perfusion is regulated by nitric oxide (NO), and polymorphisms in genes encoding for enzymes involved in NO formation and degradation (endothelial nitric oxide synthase [NOS3] and cytochrome b-235 alpha polypeptide gene [CYBA]) might contribute to vascular dysregulation observed in glaucoma. We therefore assessed the association of glaucoma with polymorphisms of NOS3 and CYBA previously associated with cardiovascular disease. We also compared the distribution of these polymorphisms in patients with high tension glaucoma (HTG) and normal tension glaucoma (NTG) and evaluated its association with vascular dysregulation in a subset of glaucoma patients. METHODS: Three hundred Caucasian patients with HTG and 127 with NTG were enrolled in the study and genotyped for G894T (rs1799983) and T-786C (rs2070744) in NOS3 and C242T (rs4673) in CYBA. RESULTS: None of these polymorphisms had a different allele or genotype distribution between HTG and NTG patients nor had the presence of vasospasms any impact. CONCLUSIONS: We studied the frequencies of a set of relevant polymorphisms of the NO system in a large cohort of glaucoma patients and found no association. These results therefore suggest the absence of a relevant relationship with different glaucoma forms in Caucasians.

PE-11, a peptide derived from chromogranin B, in the rat eye.

The aim of the study was to investigate the presence and distribution of PE-11, a peptide derived from chromogranin B, in the rat eye. For this purpose, newborn rats were injected with a single dosage of 50mg/kg capsaicin subcutaneously under the neck fold and after three months, particular eye tissues were dissected and the concentration of PE-11-like immunoreactivity was determined by radioimmunoassay. Furthermore, PE-11-like immunoreactivities were characterized in an extract of the rat eye by reversed phase HPLC. Then, the distribution pattern of PE-11 was investigated in the rat eye and rat trigeminal ganglion by immunofluorescence. As a result, PE-11 was present in each tissue of the rat eye and capsaicin pretreatment led to a 88.05% (±7.07) and a 64.26% (±14.17) decrease of the levels of PE-11 in the cornea and choroid/sclera, respectively, and to a complete loss in the iris/ciliary body complex. Approximately 70% of immunoreactivities detected by the PE-11 antiserum have been found to represent authentic PE-11. Sparse nerve fibers were visualized in the corneal and uveal stroma, surrounding blood vessels at the limbus, ciliary body and choroid and in association with the dilator and sphincter muscle. Furthermore, immunoreactivity was present in the corneal endothelium. In the retina and optic nerve, glia was labeled. In the rat trigeminal ganglion, PE-11-immunoreactivity was visualized in small and medium sized ganglion cells with a diameter of up to 30µm. In conclusion, there is unequivocal evidence that PE-11 is a constituent of capsaicin-sensitive sensory neurons innervating the rat eye and the distribution pattern is typically peptidergic in the peripheral innervation but in the retina completely atypical for neuropeptides and unique.