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Primary open angle glaucoma is a primary mitochondrial disease with oxidative stress triggering neuroinflammation, eventually resulting in neurodegeneration. This affects many other areas of the brain in addition to the visual system. Aging also leads to inflammaging - a low-grade chronic inflammatory reaction in mitochondrial dysfunction, so these inflammatory processes overlap in the aging process and intensify pathophysiological processes associated with glaucoma. Actively counteracting these inflammatory events involves optimising treatment for any manifest systemic diseases while maintaining chronobiology and improving the microbiome. Physical and mental activity also provides support. This requires a holistic approach towards optimising neurodegeneration treatment in primary open angle glaucoma in addition to reducing intraocular pressure according personalised patient targets.
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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 patients with POAG. 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, noninterventional study covering calendar years 2016-2021. RESULTS: For the adult German population (≥18 y), we estimated a POAG 1-year prevalence of 1.70% and a 1-year incidence of 0.17% in 2018; both increased with age, peaking in 80- to 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 with 2 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 with 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, 2 years after the procedure. Most patients were multimorbid highlighting the need for comprehensive care.
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Glaucoma de Ángulo Abierto , Humanos , Glaucoma de Ángulo Abierto/epidemiología , Glaucoma de Ángulo Abierto/terapia , Glaucoma de Ángulo Abierto/cirugía , Alemania/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Prevalencia , Incidencia , Adulto , Trabeculectomía , Adulto Joven , Adolescente , COVID-19/epidemiología , Costos de la Atención en Salud , Bases de Datos Factuales , SARS-CoV-2 , Terapia por LáserRESUMEN
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.
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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.
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Envejecimiento , Glaucoma , Humanos , Glaucoma/diagnóstico , Glaucoma/etiología , Factores de RiesgoRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Glaucoma , Fármacos Neuroprotectores , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Estudios Prospectivos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Glaucoma/tratamiento farmacológicoRESUMEN
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.
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Diabetes Mellitus , Glaucoma de Ángulo Abierto , Enfermedades Neurodegenerativas , Enfermedades del Nervio Óptico , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Nervio Óptico , Presión IntraocularRESUMEN
Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarctionApplication of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transitionApplication of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.
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BACKGROUND: Trabeculectomy (TE) remains one of the most frequently performed glaucoma procedures. This surgery enables sufficient reduction of intraocular pressure (IOP) and freedom from using eye drops; however, complication management and time-consuming postoperative care make many ophthalmic surgeons reluctant to include TE in their treatment regimen. AIM: This review presents the value of TE compared to other forms of filtering and nonfiltering glaucoma surgery. CONCLUSION: The use of TE is still the most effective method for lowering IOP and in comparison to other forms of glaucoma surgery in most cases enables freedom from eye drops with a subsequent high quality of life. Postoperative complications occur more frequently, but usually heal spontaneously or can be treated adequately and safely by surgery; however, TE requires intensive postoperative care, which should not be neglected. Repeated surgery due to insufficient IOP reduction is less frequent compared to other forms of glaucoma surgery.
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Glaucoma , Trabeculectomía , Glaucoma/cirugía , Humanos , Presión Intraocular , Soluciones Oftálmicas , Calidad de Vida , Trabeculectomía/métodosRESUMEN
BACKGROUND: The retrospective study provides real-world evidence for long-term clinical efficacy of electrical optic nerve stimulation (ONS) in glaucoma with progressive vision loss. METHODS: Seventy glaucoma patients (45 to 86 y) with progressive vision loss despite therapeutic reduction of intraocular pressure (IOP) underwent electrical ONS. Closed eyes were separately stimulated by bipolar rectangular pulses with stimulus intensities up to 1.2 mA sufficient to provoke phosphenes. Ten daily stimulation sessions within 2 weeks lasted about 80 min each. Right before ONS at baseline (PRE), vision loss was documented by static threshold perimetry and compared to the same assessment approximately 1 year afterwards (POST). Mean defect (MD) was defined as primary outcome parameter. Perimetries with a reliability factor (RF) of max. 20% were considered. RESULTS: Perimetry follow-up of 101 eyes in 70 patients fulfilled the criterion of a max. 20% RF. Follow-up was performed on average 362.2 days after ONS. MD significantly decreased from PRE 14.0 dB (median) to POST 13.4 dB (p < 0.01). 64 eyes in 49 patients showed constant or reduced MD as compared to baseline (PRE 13.4 dB vs. POST 11.2 dB). In 37 eyes of 30 patients, MD increased from PRE 14.9 dB to POST 15.6 dB. CONCLUSIONS: Innovative treatments that preserve visual function through mechanisms other than lowering IOP are required for glaucoma with progressive vision loss. The present long-term data document progression halt in more than 63% of affected eyes after ONS and, thus, extend existing evidence from clinical trials.
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PURPOSE: To evaluate the influence of coronary heart disease (CHD) on retinal function using a battery of electrophysiological measures. MATERIALS AND METHODS: We conducted a prospective pilot study comparing 34 patients with a confirmed diagnosis of CHD with 21 healthy participants. Further inclusion criteria were a decimal visual acuity (VA) of 0.8 or better and patient age between 40 and 80 years. All participants were divided into three groups according to the severity of CHD (1, 2 or 3 vessels involved) and one healthy control group. Testing was performed on one eye per patient, either selecting the eye with higher VA or, when equal, selecting randomly. The test procedure consisted of a pattern electroretinogram (ERG), a full-field ERG, a multifocal ERG and an ophthalmic screening examination. RESULTS: Implicit times of the b-wave measured using scotopic full-field ERG were significantly prolonged in all CHD patient groups (p < .000). Thus, full-field ERG allowed clinicians to differentiate between healthy patients and those suffering from CHD. The multifocal ERG showed significantly different results concerning the amplitude density (p < .008) in each patient group compared with the control group. CHD had a significant impact on cone-pathway function, although the severity of CHD did not correlate with functional deficiencies of cone cells. CONCLUSIONS: Confirmed coronary vascular diseases are correlated with macular cone and bipolar cell function, which can be detected by measuring electrophysiological retinal signals.
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Enfermedad Coronaria , Electrorretinografía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Coronaria/diagnóstico , Electrorretinografía/métodos , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , RetinaRESUMEN
An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.
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PURPOSE: Nesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development. METHODS: In this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9±3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3±2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors. RESULTS: Sex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-γ, Interleukin-1ß, IL-2, 4, 5, 6, 7, 10, 12 and TNF-α) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05). CONCLUSION: As a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.
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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.
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Artritis Reumatoide , Hipertensión , Adulto , Artritis Reumatoide/diagnóstico , Estudios Transversales , Humanos , Hipertensión/diagnóstico , Persona de Mediana Edad , Pruebas del Campo Visual , Campos VisualesRESUMEN
PURPOSE: Patient satisfaction is important in the treatment of glaucoma. Suboptimal compliance and impaired long-term outcome are a likely result of poor tolerability. The present multicentre, international, transverse, epidemiological survey was conducted to assess the satisfaction of patients who had received preservative-free latanoprost (PFL) for at least 3 months. PATIENTS AND METHODS: A total of 1872 patients from 6 European countries, treated with PFL for at least 3 months, were included in this survey. Prior to PFL treatment, patients were to be treatment naïve or currently treated for their glaucoma. During a single routine consultation, patients completed a questionnaire concerning global satisfaction and satisfaction based on tolerability. RESULTS: In total, 76.2% had been previously treated; 69.4% had received preserved and 6.8% preservative-free (PF) topical treatment. After 3 months of PFL treatment, a large majority of patients (95.3%) were satisfied or very satisfied with their PFL treatment and were, overall, significantly (p<0.0001) more satisfied with PFL than with their previous treatment; 4.2% were either unsatisfied or very unsatisfied. Overall, 97.3% of originally treatment-naïve patients were satisfied (50.1%) or very satisfied (47.2%) with their PFL. Ocular surface disease was diagnosed in 9.2% of patients (n=173) and was mainly mild (76.9%). Patient satisfaction with PFL was very high. CONCLUSION: PFL may be considered a valuable first-choice treatment in glaucoma patients.
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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.