Neuroprotective Effects of Anti-diabetic Drugs in the Treatment of Patients with Diabetes and Glaucoma or at High Risk for Glaucoma. / Neuroprotektive Wirkungen von Antidiabetika in der Therapie von Patienten mit Diabetes und Glaukom oder hohem Glaukomrisiko.

There is an association between glaucoma and several risk factors and metabolic diseases, such as type 2 diabetes mellitus. Diabetes mellitus leads to neurodegenerative changes, both peripherally and in the brain. This might be a shared pathophysiology and etiology for both glaucoma and diabetes. It is interesting that drugs for the treatment of diabetes seem to have neuroprotective properties independent of their blood sugar reduction. Although prospective, randomized, clinical studies are still missing, particularly metformin and glucagon-like peptide receptor agonists (GLP 1 RA) seem to have neuroprotective effects. Sulphonylureas (e.g., glibenclamide, glimepiride) are still used. They frequently potently reduce blood pressure but may be less neuroprotective. In the present review, the evidence for neuroprotective effects of the different antidiabetic drugs is presented and a possible differential therapy for patients with diabetes and glaucoma, or at high risk of glaucoma, will be discussed.

Influence of Diabetes Mellitus on Glaucoma-Relevant Examination Results in Primary Open-Angle Glaucoma. / Einflussnahme des Diabetes mellitus auf glaukomrelevante Untersuchungsergebnisse beim primären Offenwinkelglaukom.

Primary open-angle glaucoma (POAG) is no longer considered an isolated eye pressure-dependent optic neuropathy, but a neurodegenerative disease in which oxidative stress and neuroinflammation are prominent. These processes may be exacerbated by additional systemic diseases. The most common are arterial hypertension, dyslipidemia, and diabetes mellitus. Using diabetes mellitus as an example, it will be shown how far-reaching the influence of such a systemic disease can be on both the functional and the structural diagnostic methods for POAG. This knowledge is essential, since these interferences can lead to misinterpretations of POAG, which can also affect therapeutic decisions.

Influence of ACPA-positive rheumatoid arthritis on visual field testing in patients with arterial hypertension: A comparative cross-sectional study.

PURPOSE: To evaluate a possible influence of anti-cyclic citrullinated peptide autoantibodies (ACPA) - positive rheumatoid arthritis (RA) on visual field (VF) testing in patients with arterial hypertension (aHT). METHODS: We conducted an observational cross-sectional study comparing patients with ACPA-positive RA and aHT, patients with aHT and healthy subjects. Further inclusion criteria were visual acuity (VA) of 0.8 or better and age between 40 and 60 years. VF testing was performed with standard automated achromatic perimetry (SAP), short wavelength automated perimetry (SWAP) (Octopus 300® ) and flicker perimetry (Pulsar® ). Results were analysed for a possible correlation with blood pressure or RA-activity. RESULTS: Twenty subjects with RA and aHT, 26 patients with aHT and 22 healthy participants were examined. Significant differences were found for mean sensitivity (MS) in SWAP comparing RA-patients with healthy participants (ΔMS -3.06, p = 0.001) and with hypertensive patients (ΔMS -2.32, p = 0.007). In SAP we observed a significant difference between patients with RA and healthy subjects regarding loss variance (LV) (ΔLV = +9.77, p = 0.004). Flicker perimetry did not demonstrate significant differences between groups. A correlation of VF changes with blood pressure level or RA-activity was not observed. CONCLUSION: Patients with ACPA-positive RA and aHT showed significant impairment of VF performance in SWAP compared to patients with aHT alone and healthy subjects. SAP also revealed a significant difference of LV between RA-patients and healthy subjects. aHT does not seem to induce functional changes in VF testing alone.

The Impact of Artificial Tear Viscosity on the Results of Optical Coherence Tomography. / Einfluss der Tränenersatzmittel-Viskosität auf die Messergebnisse der optischen Kohärenztomografie.

BACKGROUND: In earlier studies, an irregular tear film could be responsible for artifacts in imaging procedures in ophthalmology. As a result, this study will investigate the influence of hyaluronic acid-containing tear substitutes of different viscosities on the measurement results of optical coherence tomography and on the non-invasive tear film break-up time. METHODS: The study included three sessions in which three hyaluronic acid tear substitutes of different viscosities (Hylo-Vision 0.1%, 0.2%, 0.3%, OmniVision GmbH, Puchheim, Germany) were applied to each subject. In 20 healthy volunteers, the non-invasive tear film break-up time was measured before and after the application of the tear substitutes using Keratograph 5M (Oculus GmbH, Wetzlar, Germany) and optical coherence tomography using 3D OCT-2000 (Topcon, Hamburg, Germany). RESULTS: The median age of the volunteers was 28.5 years. 11 women (55%) and 9 men (45%) were examined. The non-invasive tear film break-up time improved significantly (p = 0.027) after the application of 0.3% hyaluronic acid. In the study, no significant difference was found in all OCT parameters used before and after application of the different viscous hyaluronic acid-containing tear substitutes. CONCLUSION: In this study, no influence of tear substitutes containing different viscosities of hyaluronic acid on the measurement results of optical coherence tomography could be determined. Therefore, 0.1%, 0.2% and 0.3% hyaluronic acid can be applied to the patient to improve the corneal surface before the examination with optical coherence tomography, without influencing the measurement results of optical coherence tomography.

[Secondary Neuroprotection in Glaucoma Through the Concepts of Complementary Drug Therapy]. / Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte.

Primary open angle glaucoma (POAG) is currently considered a neurodegenerative systemic disease. The individualised reduction in intraocular pressure alone does not do justice to the complex events in the chronic course of the disease, so that accompanying drug therapy concepts are useful. Based on four therapeutic strategies, such as the improvement of the mitochondrial respiratory chain with coenzyme Q10, the stabilisation of the mitochondrial and cellular plasma membranes with citicoline, the reduction in oxidative stress in the eye and in the body with curcumin and the improvement of fat metabolism, especially LDL cholesterol, with the application of statins, an insight into possible additive therapeutic approaches will be provided. Since neuroprotective therapies as monotherapies are unlikely to be very promising, they are more likely to consist of a combination of different therapeutic approaches.

[Perioperative Anti-inflammatory Treatment in Glaucoma Surgery]. / Perioperative antientzündliche Therapie im Rahmen der Glaukomchirurgie.

Many clinical studies have demonstrated the benefit of topical anti-inflammatory medication before and after glaucoma surgery, especially for trabeculectomy, and that they improve the long term outcome. Pre- and postoperative topical steroids improve the outcome of trabeculectomy, but duration and intensity of treatment should be adapted individually. Systemic steroid or oral immunomodulation have significant impact on the outcome in uveitic glaucoma, but not in other glaucoma subtypes. Additional topical treatment with non-steroidal anti-inflammatories is an option in combined cataract-glaucoma surgery. Anti-inflammatory treatment after selective laser trabeculoplasty is not necessary, but relieves pain after argon laser trabeculoplasty and laser cyclophotocoagulation. Intravitreal application of steroids in glaucoma surgery must be critically evaluated and must consider the risk of a rise in secondary intraocular pressure.

[Evaluation of Changes in Corneal Biomechanics in Patients with Systemic Sclerosis]. / Klinische Untersuchung zur Veränderung der kornealen Biomechanik bei Patienten mit systemischer Sklerodermie.

INTRODUCTION: Our study compares the biomechanical properties of the cornea in patients with long-term pre-existing (for at least 10 years) systemic sclerosis (SSc) with those of healthy suspects. MATERIAL/METHODS: The examination was performed in 14 systemic SSc patients and 38 healthy volunteers. Non-invasive assessment of corneal biomechanical parameters, including central corneal thickness (CCT), corneal hysteresis (CH) and corneal resistance factor (CRF), was performed in one randomised study eye in accordance with a standardised protocol. Intraocular pressure (IOP) values were analysed using different measuring techniques, including Goldmann applanation tonometry (GAT), dynamic contour tonometry (DCT) and Ocular Response Analyzer® (ORA)-based non-contact tonometry (NCT), GAT-correlated IOP (IOPgat) and CCT-compensated-IOP (IOPcc). RESULTS: When measured with DCT and ORA-based NCT, IOP levels were significantly lower in SSc patients than in the control group (DCT IOP: p = 0.048, NCT IOPgat: p = 0.002, NCT IOPcc: p < 0.001). CCT was also significantly reduced in the SSc (p = 0.001). There were no statistically significant differences between the groups in CH and CRF. The difference between the corrected values (CHcorr - CRFcorr) was negative in the two groups. This was slightly lower for the SSc patients (delta = - 0.83) than for the control group (delta = - 0.66). For SSc patients, there were highly significant negative correlations between CH and CRF and between CHcorr and CRFcorr. In contrast, in the control group there was a non-significant positive correlation between age and biomechanical properties. CONCLUSION: In the course of the disease SSc leads to various alterations in connective tissue, which can also involve corneal tissue. CCT becomes significantly thinner and simultaneously partially loses elastic properties and gains viscosity. This accounts for reduced IOP values with dynamic contour tonometry as well as with ORA-tonometry (Goldmann-correlated IOP, CCT-compensated IOP). This distinct pre-existing significant negative correlation between age and CH and CRF values in patients with SSc could be due to slight regression of the viscous components and diminution of corneal damping capacity.

[Mitochondrial Dysfunctions and Role of Coenzyme Q10 in Patients with Glaucoma]. / Mitochondriale Dysfunktion und Bedeutung von Coenzym Q10 beim Glaukom.

Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA). In contrast, secondary mitochondrial dysfunctions are caused by environmental factors. In recent years, there has been growing evidence that mitochondrial dysfunctions play an important role in many common eye diseases, such as glaucoma, dry eye, diabetic retinopathy, cataract and age-related macular degeneration (AMD). This article summarises current knowledge of mitochondrial dysfunctions and the role of coenzyme Q10 (CoQ10) as a possible treatment option - with a special focus on glaucoma.

[Risk Factors and Therapeutic Goals for Primary and Secondary Cardiovascular Prevention: Significance for the Glaucoma Patient]. / Risikofaktoren und Zielwerte in der kardiovaskulären Primär- und Sekundärprävention: Bedeutung für das Glaukom.

Hypertension, diabetes mellitus and dyslipidaemia are among the most important cardiovascular risk factors. In addition, there is an association with the development and progression of glaucoma. During the last years, there has been an intense discussion concerning optimal treatment goals for these risk factors. Recently, the American Heart Association has defined a blood pressure greater than 130/80 mmHg as hypertension and the European guidelines will follow this definition. These lower blood pressure limits increase the risk for a too strict blood pressure treatment with night values, which might be too low for glaucoma patients. In contrast, the treatment goals for LDL cholesterol should be as low as possible ("the lower the better"). There is a more differentiated picture concerning treatment goals for diabetes mellitus. For elderly patients, which is the main group of the glaucoma patients, a less intense blood sugar reduction is currently recommended with an HbA1c value of above 7%. The present paper summarizes the significance of cardiovascular risk factors and the respective treatment goals for the therapy of patients with glaucoma.

Epiretinal membrane as a source of errors during the measurement of peripapillary nerve fibre thickness using spectral-domain optical coherence tomography (SD-OCT).

PURPOSE: We aimed to examine the extent to which measurement errors in the determination of retinal nerve fibre layer (RNFL) using spectral-domain optical coherence tomography (SD-OCT) occur in cases of epiretinal membrane and whether systematic deviations are found in the values obtained. METHODS: A macular scan and a circumpapillary scan were performed on 97 eyes of 97 patients using SD-OCT. Group 1 comprised 53 patients with epiretinal membrane at an age of 70 ± 4.8 years (median ± average absolute deviation). Group 2 consisted of 44 patients without any macular pathologies (median age 70 ± 5.8 years). Differences in the thickness of the RNFL and segmentation errors in the detection of the RNFL were recorded quantitatively in both groups and checked for statistical significance using non-parametric tests. RESULTS: The median central retinal thickness in Group 1 was 357 ± 79 µm (median ± average absolute deviation), and in Group 2 it was 270 ± 11 µm (p < 0.001). The result of the quadrant-by-quadrant measurement of the average RNFL in Group 1 and Group 2, respectively, was: temporal 88 ± 17 and 73 ± 9 µm, inferior 121 ± 17 and 118 ± 15 µm, nasal 87 ± 15 and 89 ± 14 µm and superior 115 ± 15 and 114 ± 9 µm. Temporally, the difference was statistically significant (p < 0.001). Segmentation errors of the RNFL were found in 19 of 53 eyes (35.8 %) in Group 1 and in no eyes (p < 0.001) in Group 2. CONCLUSIONS: In eyes with epiretinal membrane, measuring errors in the SD-OCT occur significantly more frequently than in eyes without any retinal pathologies. If epiretinal membrane and glaucoma are present simultaneously, the results of the automated RNFL measurement using SD-OCT should be critically scrutinised, even if no papillary changes are visible clinically.

Protection against Oxidative Stress by Coenzyme Q10 in a Porcine Retinal Degeneration Model.

Oxidative stress plays an important role in neurodegenerative diseases, including glaucoma. Therefore, we analyzed if the antioxidant coenzyme Q10 (CoQ10), which is also commercially available, can prevent retinal degeneration induced by hydrogen peroxide (H2O2) in a porcine organ culture model. Retinal explants were cultivated for eight days, and H2O2 (500 µM, 3 h) induced the oxidative damage. CoQ10 therapy was applied (700 µM, 48 h). Retinal ganglion cells (RGCs) and microglia were examined immunohistologically in all groups (control, H2O2, H2O2 + CoQ10). Cellular, oxidative, and inflammatory genes were quantified via RT-qPCR. Strong RGC loss was observed with H2O2 (p ≤ 0.001). CoQ10 elicited RGC protection compared to the damaged group at a histological (p ≤ 0.001) and mRNA level. We detected more microglia cells with H2O2, but CoQ10 reduced this effect (p = 0.004). Cellular protection genes (NRF2) against oxidative stress were stimulated by CoQ10 (p ≤ 0.001). Furthermore, mitochondrial oxidative stress (SOD2) increased through H2O2 (p = 0.038), and CoQ10 reduced it to control level. Our novel results indicate neuroprotection via CoQ10 in porcine retina organ cultures. In particular, CoQ10 appears to protect RGCs by potentially inhibiting apoptosis-related pathways, activating intracellular protection and reducing mitochondrial stress.

Epidemiology and Treatment of Patients With Primary Open Angle Glaucoma in Germany: A Health Claims Data Analysis.

PRCIS: Based on a large administrative database of German claims data, our study provides current estimates of the prevalence and incidence of primary open-angle glaucoma (POAG) in Germany and describes selected outcomes for prevalent POAG patients. PURPOSE: To estimate the prevalence and incidence of POAG in Germany, to describe the patient population in terms of comorbidity burden, routine care, and overall healthcare resource utilization (HCRU) and associated costs, and to describe treatment patterns over time in patients undergoing relevant laser procedures. MATERIALS AND METHODS: Based on anonymized German claims data, we carried out a retrospective, non-interventional study covering calendar years 2016 to 2021. RESULTS: For the adult German population (≥18 y), we estimated a POAG one-year prevalence of 1.70% and a one-year incidence of 0.17% in 2018; both increased with age, peaking in 80-89 year-olds. Prevalence and incidence were lower in 2020 (1.65% and 0.16%, respectively), the first year of the SARS-CoV-2 pandemic. Most patients solely received topical treatment. Most surgically-treated patients underwent laser trabeculoplasty, followed by laser iridotomy, trabeculectomy, and filtration operations with implant. In patients undergoing laser trabeculoplasty, the treatment regimen was nearly unchanged in the second year after, compared to two years before the procedure. Multimorbidity was commonly observed; 75.5% of patients had arterial hypertension and 50.0% had disorders of lipoprotein metabolism and other lipidemias, compared to 60.1% and 39.2%, respectively, in an age- and sex-matched control sample. CONCLUSIONS: Our study provides insights into epidemiology and routine care of POAG in Germany and HCRU in prevalent patients. There was little change in treatment regimens in patients who underwent laser trabeculoplasty, two years after the procedure. Most patients were multimorbid highlighting the need for comprehensive care.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

Age-corrected reference values for the Heidelberg multi-color anomaloscope.

BACKGROUND: To determine reference values for the HMC anomaloscope (Heidelberg multi-color anomaloscope) of healthy subjects. METHODS: One hundred and thirteen healthy subjects were divided into four age groups: <20 years of age (ten female, five male), 20-39 years of age (23 female, 15 male), 40-59 years of age (23 female, ten male) and >60 years of age (nine female, 18 male). Match midpoint, matching range (MR) and anomaly quotient (AQ), according to the Moreland equation [blue (436 nm) + blue-green (490 nm) = cyan (480 nm) + yellow (589 nm)] and according to the Rayleigh equation [green (546 nm) + red (671 nm) = yellow (589 nm)] were determined. The neutral adaptation was done showing white light every 5 seconds in absolute mode and every 15 seconds in relative mode. RESULTS: The mean match midpoint according to the Rayleigh equation was 43.9 ± 2.6 scale units in absolute mode. It was highest between 20-39 years (45.2 ± 2.2) and lowest in subjects >60 years of age (42.2 ± 2.2). The mean MR in absolute mode was 3.1 ± 3.5 scale units with a maximum >60 years (4.4 ± 4.4). The MR in relative mode was between 1.6 ± 1.9 (20-39 years) and 4.4 ± 3.8 (>60 years). The resulting mean AQ was 1.01 ± 0.15 in both modes. The mean match midpoint of the Moreland equation was 51.0 ± 5.2 scale units in absolute mode. It was highest between 20-39 years (52.5 ± 5.7), and lowest in subjects >60 years of age (48.7 ± 3.6). The mean MR according to the Moreland equation was lower in absolute mode (13.4 ± 15.6) than in relative mode (16.2 ± 15.2). The mean resulting AQ was 1.02 ± 0.21 in both modes. CONCLUSION: The values of this study can be used as references for the diagnosis of red-green and blue perception impairment with the HMC anomaloscope.