Risk Factors of Age-Related Macular Degeneration in a Population-Based Study: Results from SHIP-TREND-1 (Study of Health in Pomerania-TREND-1).

BACKGROUND Age-related macular degeneration (AMD) is the most common cause of visual impairment in the elderly population in industrialized countries. The Study of Health in Pomerania (SHIP) with its cohort SHIP-TREND was designed to investigate risk factors and clinical disorders in the general population of northeast Germany. This work focused on the first follow-up of SHIP-TREND and determined associated modifiable risk factors of AMD. Modifying risk factors is important to slow the progression of early AMD as there is currently no treatment for the late stage of geographic atrophy. Understanding AMD-associated risk factors also plays an important role in the development of therapeutic concepts. MATERIAL AND METHODS Between 2016 and 2019, data were collected from a total of 2507 initially randomly selected subjects from the general population aged 28 to 89 years. Non-mydriatic fundus photography of the right eye was performed in 2489 subjects. Grading of AMD was performed using the Rotterdam classification system. RESULTS We included 1418 gradable fundus photographs in the analysis. The risk of AMD changes increased with age and was positively correlated with HDL cholesterol, fT3, and low educational level. In men, BMI and cigarette smoking were also positively associated with AMD changes. CONCLUSIONS This study emphasizes the consideration of various metabolic pathways for the development of therapeutic concepts.

Fetal eye ultrasound: Normal anatomy, abnormal findings, and clinical impact. / Ultraschall des fetalen Auges: Normale Anatomie, abnorme Befunde und klinische Bedeutung.

Until now, ultrasound examination of the fetal eyes has not played an important role in prenatal diagnosis. National and international guidelines are generally confined to documentation of the presence of the orbits and the lenses. However, in recent years, with the advent of high-resolution ultrasound technology and increasing knowledge of prenatal medicine and genetics, careful examination of the fetal eye has enabled the detection of many ocular malformations before birth. This article provides an overview of the anatomy related to the development of the fetal eye and covers the following conditions: hypertelorism, hypotelorism, exophthalmos, microphthalmos, coloboma, cataract, persistent hyperplastic primary vitreous, retinal detachment, dacryocystocele, and septooptic dysplasia, etc. It is designed to illustrate the spectrum of ocular malformations and their appearance on prenatal ultrasound and to discuss their clinical impact and association with various syndromes.

[Ophthalmologic Evaluation of Fitness to Drive]. / Augenärztliche Beurteilung der Kraftfahreignung.

The ophthalmologist must know the essential principles of the driving fitness assessment. In the case of applications for a driving license renewal, it must always be clarified before the examination whether the fitness to drive is to be checked in accordance with the special regulation for holders of a driving license issued up to December 31, 1998 (see Annex 6 to § 12 of the FeV under 2.2.3 Special regulations for the old German Road Traffic Licensing Regulations). Within the scope of grandfathering, this continues to be valid only for the so-called old holders. A categorization of the manifold concerns regarding fitness to drive or driving ability in everyday practice makes it easier for the ophthalmologist to make a factually justified decision in individual cases. In particular, a distinction must be made between the medical assessment of subjects as applicants for a driving license (first-time applicants or renewal applicants) according to the German Driving License Ordinance (FeV) and the consultation of patients with chronic eye diseases [duty to inform according to the German Patients' Rights Act (PRG) and the German Civil Code (BGB), German Driving License Ordinance (FeV)]. The German Driving License Ordinance contains precise specifications for standardized testing of visual acuity and visual field as the most important partial functions of the eye. A special feature of the identified performance deficits of the eyes is that compensation by other bodily functions or supplementary technical equipment on the vehicle is not yet possible. The ophthalmologist therefore often has the task and responsibility of balancing the individual desire for mobility, in the case of professional drivers even the preservation of their jobs on the one hand, and the general societal need for safety on the other.

Smell and taste in idiopathic blepharospasm.

The pathophysiology of blepharospasm is incompletely understood. Current concepts suggest that blepharospasm is a network disorder, involving basal ganglia, thalamus, cortex, and, possibly, the cerebellum. Tracing, imaging, and clinical studies revealed that these structures are also concerned with olfaction and taste. Because of this anatomical overlap, dysfunction of the chemical senses in blepharospasm is expected. Injections of botulinum toxin into the eyelid muscles are the first-line treatment of blepharospasm. Yet, the effects of botulinum toxin on the chemical senses have not been systematically assessed. To contribute to a better understanding of blepharospasm, olfactory and gustatory abilities were assessed in 17 subjects with blepharospasm and 17 age-/sex-matched healthy controls. Sniffin Sticks were used to assess odor threshold, odor discrimination, and odor identification. Results of these three Sniffin Sticks subtests were added to the composite olfactory score. The Taste Strips were applied to assess taste. In an adjacent study, we assessed the sense of smell and taste in eight subjects with blepharospasm before and 4 weeks after botulinum toxin treatment. Subjects with blepharospasm had significantly lower (= worse) scores for odor threshold and for the composite olfactory score than healthy controls, while odor discrimination, odor identification, and the composite taste score were not different between groups. The adjacent study revealed that botulinum toxin did not impact the chemical senses. In this study, subjects with blepharospasm had a lower (= worse) odor threshold than healthy controls. As olfaction is important in daily life, findings justify further research of olfaction in blepharospasm.

Contextual Assessment of Retinal Injuries - Tasks of the Ophthalmological Expert. / Zusammenhangsgutachten bei Verletzungen der Netzhaut ­ Aufgaben des augenärztlichen Sachverständigen.

The ophthalmologic assessment of causal relationships is subject to formal guidelines, depending on the legal field (social law in the statutory accident insurance, civil law in the private accident insurance). After determining all objective and subjective findings of the individual case with complete recording of the medical facts, the ophthalmologist has the task of making a summarizing assessment of the existing cause-and-effect relationship. With regard to the distinction between retinal damage caused by an accident or retinal disease not caused by an accident, it is necessary to weigh up the natural causality according to the state of medical experience on the basis of the criteria strength of association, consistency, specificity, temporal sequence, dose dependence, agreement with previous findings, experimental reliability and analogous consideration. All records of medical findings from the patient's medical history and the individual description of the accident must be included in the expert opinion. In the case of several competing causes (often accident and pre-existing damage), the social law in the statutory accident insurance must present the causal contributions with roughly estimated probabilities. In civil law, valid for the private accident insurance, the existence of partial causality (approx. 25, 50, 75%) must be evaluated.

[The ophthalmological expert opinion in different fields of law]. / Das augenärztliche Gutachten in unterschiedlichen Rechtsgebieten.

The ophthalmological appraisal differs significantly in the different areas of law, so there are some different causalities and standards of proof and, above all, the assessment is very different. For the three important sub-areas of private accident insurance, statutory accident insurance as well as disability law and social compensation law, there are abstract tabular guidelines which form the essential basis for a comparable and thus fair assessment. The basics of the assessment in these fields of law are presented in a comparative way, with particular emphasis on causality.

Age-Related Macular Degeneration and Associated Risk Factors in the Population-Based Study of Health in Pomerania (SHIP-Trend).

BACKGROUND Age-related macular degeneration (AMD) is the leading cause of visual impairment in developed countries, especially in the older population. The Study of Health in Pomerania (SHIP) is a population-based study designed to investigate risk factors and clinical disorders in the general population. In the present study, we analysed the AMD prevalence and risk factors in the north-eastern German population. MATERIAL AND METHODS From 2008 to 2012, we collected data among participants ages 29-79 years. The study population consisted of 4420 individuals. Non-mydriatic retinal photographs were taken of 3934 participants. AMD stages were graded according to the Rotterdam Classification System and the International Classification System. RESULTS Photographs from 1854 participants were available for grading. The baseline examinations showed small hard drusen (<63 µm, stage 0b and 0c) were present in 10.7% of the participants (stage 0b in 7.5% and stage 0c in 3.2%). Earliest signs of AMD were detected in 28.68% (stage 0b in 7.5% and stage 1b in 21.18%). Late AMD (geographic atrophy and neovascular AMD, stages 4a and 4b) were identified in 0.43% (stage 4a in 0.16% and stage 4b 0.27%). Risk of AMD increased significantly with age and higher body mass index, waist circumference, hip circumference, and weight-waist-ratio. Smoking, sex, systolic and diastolic blood pressure, HbA1c, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride were not associated with AMD in this study. CONCLUSIONS The prevalence of AMD increases with age and obesity-associated factors. These results must be verified in the follow-up. Data concerning the incidence of AMD will be available after the 5- and 10-year follow-ups.

Prevalence of impaired functional reading ability and its association with quality of life, daily activity, mobility and social participation among general older adults in Germany.

BACKGROUND: The prevalence of visual impairment and of impaired functional reading ability rapidly increase with age. However, functional reading ability is essential for an autonomous lifestyle. We analyzed the prevalence of impaired functional reading ability in the general elderly population and the association of impaired functional reading ability with quality of life, daily activities, mobility, and social participation. METHODS: Cross-sectional data from a population-based cohort were analyzed. Participants aged ≥65 years were tested for their functional reading ability using (1) Nieden charts (cognitive reading ability) and (2) a test in which a telephone number had to be found (reading comprehension). Prevalences of impaired functional reading ability were calculated. In multivariable regression models, the associations of cognitive reading ability (1) with quality of life, daily activities, mobility, and social participation were examined. RESULTS: 60 of 780 participants (7.69%) were able to read the third last text of the Nieden test (good cognitive reading ability), whereas 7 participants (0.9%) were unable to read any of the texts. 716 participants (91.8%) identified the phone book entry successfully (good reading comprehension). Multivariable regression models revealed no significant associations of the cognitive reading ability (1) with quality of life, daily activities, social participation, and mobility. CONCLUSION: Our results showed a high prevalence of impaired cognitive reading ability (1). Reading comprehension (2) was slightly affected. The loss of cognitive reading ability usually progresses over years; signs and symptoms might remain unrecognized when compensated by other functions.

[Static Retinal Vessel Analysis in Population-based Study SHIP-Trend]. / Statische Gefäßanalyse der retinalen Blutgefäße in einer populationsbasierten Kohorte unter Berücksichtigung des Diabetes mellitus.

BACKGROUND: Interdisciplinary investigations of possible connections between general diseases and ophthalmological changes are difficult to perform in the clinical environment. But they are gaining in importance as a result of the age-related increase in chronic diseases. The collection of health-related parameters in the Study of Health in Pomerania (SHIP) project allows to derive conclusions for the general population. METHODS: The population-based SHIP trend study was conducted between 2008 and 2012 in Greifswald. The baseline cohort included 4420 subjects (response 50.1%) at the age of 20 to 84 years. The pre-existence of arterial hypertension, diabetes mellitus and smoking status were questioned in a standardized questionnaire, the blood pressure and the HbA1c were determined by the laboratory. The vascular diameter of retinal arterioles and venules were determined by means of non-mydriatic fundus images and the retinal arterial (CRAE) and venous equivalent (CRVE) were calculated therefrom. The association of diabetes mellitus, HbA1c, smoking status and blood pressure with the retinal vascular parameters was tested for age and sex with linear regression models. RESULTS: In 3218 subjects with evaluable standardized fundus photographs, significant associations of elevated HbA1c (> 6.5%), smoking status and systolic and diastolic blood pressure were found with the retinal vessel widths CRAE and CRVE. Anamnestic diabetes mellitus, on the other hand, was not associated with any of the vascular parameters. CONCLUSION: This research study reveals a relevant correlation between general diseases and the retinal blood flow in the eye. Therefore, general diseases can induce ophthalmological changes and eye examination can provide information for the assessment of general diseases.

Cross-sectional association between oral health and retinal microcirculation.

AIM: To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. METHODS: We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR < 0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. RESULTS: Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [ß = -0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [ß = -0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [ß = 3.80 (0.61; 6.98 95%-CI)], mean probing depth [ß = 1.86 (0.23; 3.49 95%-CI)] and mean attachment level [ß = 1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [ß = 0.91 (0.14; 1.69 95%-CI)]. CONCLUSIONS: Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.

Evaluation of a visual acuity test using closed Landolt-Cs to determine malingering.

PURPOSE: To evaluate a visual acuity test (VAT) with unexpected optotypes to detect malingering. METHODS: We tested two groups. Group 1 consisted of 20 individuals with normal best corrected visual acuity (BCVA). Group 2 included participants with ocular diseases and reduced BCVA. All subjects underwent a VAT proposed by Gräf and Roesen to assess suspected malingering. This test used 36 charts with one Landolt-C per page. The first 20 optotypes were Landolt-Cs, while at positions 21, 26, 30, and 34 closed rings were presented. The testing distance was adapted to 50% of the test person's visual acuity. The test person was requested to name the gap direction of the Landolt-C within 3 s. The complete testing conversation was recorded digitally to determine response latency for each optotype from the audio tracks. RESULTS: The average response time was 0.46 s in group 1 and 0.45 s in group 2 for the first 20 Landolt-Cs. In both groups the response time was significantly extended (p < 0.05) for the first closed ring compared to the mean of the first 20 Landolt-Cs, (group 1: 2.9 s; group 2: 2.3 s). The following three closed rings had also longer response times. However, these differences were not significant. CONCLUSIONS: Our results suggest that the proposed test may be helpful to evaluate ocular malingering. The testing procedure appeared to be feasible and showed good repeatability. The fast training effect may be a limitation for malingering detection.

[Diabetic retinopathy--Current aspects of therapy]. / Diabetische Netzhauterkrankungen. Aktuelle Aspekte in der Therapie.

Pathological changes of the small blood vessels are the main risk for diabetic retinopathy. A distinction is made between proliferative and non-proliferative processes. The diabetic macular edema can manifest itself at any stage of the diabetic retinopathy and poses a serious threat to vision and quality of life. Evidence based therapy primarily focuses on laser coagulation. Laser coagulation suspends progression of the disease and is used particularly for extrafoveolar edema. Especially a pathological swelling, such as the cystoid edema, in this central part of the retina, can cause a rapid deterioration of vision. The treatment of cystoid macular edema with intravitreal application of drugs is a widespread therapeutical approach. Invasive therapeutical drug application into the vitreous cavity has to be sterile in order to prevent infection. The usage of VEGF (Vascular endothelial growth factor) antagonists is an effective treatment for the diabetic macular edema. Several drugs are now available for intravitreal injection. Nevertheless a small number of medical drugs regularly administered to patients still have to be approved by the authorities (off-label use). One can distinguish mainly between VEGF antagonist (growth factor antagonist) like ranibizumab, aflibercept and bevacizumab and steroid therapy which includes dexamethasone, fluocinolone and triamcinolone.

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity). Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. Results: Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses. Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.

Nail projectiles propelled by a mason's lacing cord: an experimental approach.

The recent clinical observation of two unintentional penetrating ocular and cerebral injuries due to 90-mm construction nails gave occasion to an experimental study to check the alleged trauma mechanism for plausibility. Both casualties reported that they had attached a mason's lacing cord to the masonry using a nail as anchoring when suddenly the nail was yanked from its moorings and propelled like a missile by the overstretched lacing cord. As to the best of the authors' knowledge, this mechanism of injury has not yet been reported in any of the literature; it was the aim to find an experimental approach to review the plausibility of the alleged sequence of events leading to the accidents. The tensile strength at break and strain at break of different mason's lacing cords (diameter of 1 and 2 mm) were measured according to DIN EN ISO 2062 by using a tensile testing machine. Based on the maximum spring energy of the lacing cords, which was determined 174.9 J for the 1-mm cord (length 10 m) and 747.4 J for the 2-mm cord (length 10 m), the maximum possible velocity of the nails as projectiles was calculated to be 243.5 m/s for the 1-mm cord and 503.4 m/s for the 2-mm cord. The critical elongation a cord of a certain length has to be stretched to deliver enough kinetic energy to a 90-mm nail to surpass the threshold velocity for skin penetration, which was investigated by Sellier (1977) to be approximately 18 m/s, was also calculated. To conclude, the energy delivered by the cords is high enough to surpass the rather low threshold velocity of nails. The details of how these accidents occurred, which seemed questionable at first, can be reasonably explained by trauma biomechanics.

Keratoconjunctivitis as a Single Entity in X-linked Agammaglobulinemia?

PURPOSE: To report a case of a male patient with a severe corneal and conjunctival immunopathy likely caused by an X-linked agammaglobulinemia. METHODS: A clinical case report with observation results from 2001-2021. RESULTS: A severe corneal immunopathy of both eyes is reported in a retrospective long-term observation of nearly twenty years in a 32-year-old male patient with X-linked agammaglobulinemia (XLA). A chronic progressive corneal scarring with a loss of visual acuity and typical symptoms of a phlyctenular keratoconjunctivitis were observed. CONCLUSION: Whereas steroid eye drops like dexamethasone could control the symptoms and the corneal scarring progression as short time therapy options, ciclosporin A eye drops showed problems in therapy adherence in long-time use. Antibiotic eye drops supported the anti-inflammatory therapy effects, but no typical pathogen was detected. Antineovascular subconjunctival application did not show any relevant effect in one-time use. Artificial tears were needed as basic therapy.

Relationship of systemic blood pressure with ocular perfusion pressure and intraocular pressure of glaucoma patients in telemedical home monitoring.

BACKGROUND: We evaluated the relation of systemic blood pressure with intraday variations in ocular perfusion pressure and intraocular pressure in patients with primary open-angle glaucoma in a telemedical home monitoring scenario. MATERIAL/METHODS: In the project Teletonometry Mecklenburg-Vorpommern (TTMV) patients were equipped with a home monitoring system for 24-hour self-measurements of intraocular pressure and blood pressure for a period of six months. All measurements were transmitted via telephone modem to an electronic patient record. Ocular perfusion pressure (OPP) was automatically calculated from self-measurements of intraocular pressure (IOP), systolic (SBP) and diastolic blood pressure (DBP) using the equation: OPP=[2/3*(2/3*DBP+1/3*SBP)]-IOP. We present the temporal characteristics of 70 patients with primary open-angle glaucoma based on 3282 self-measurements. RESULTS: The diurnal ocular perfusion pressure trend showed four characteristic phases (7am - 12am, 12am - 6pm, 6pm - 10pm, and 10pm - 7am). Between 7am and 12am ocular perfusion pressure and simultaneously systolic and diastolic blood pressure were significantly depressed compared to all other phases (p<0.05) whereas intraocular pressure showed no significant shifting. Instead intraocular pressure was significantly depressed between 6pm and 10pm (p<0.05) where ocular perfusion pressure reached the highest intraday values. CONCLUSIONS: We found that ocular perfusion pressure in patients with primary open-angle glaucoma showed remarkable circadian fluctuations. A significant decrease in the morning was associated with significantly depressed systolic and diastolic blood pressure levels. In addition we observed normal intraocular pressure values in the morning but a significant decrease in the evening which did not affect ocular perfusion pressure. These conclusions strengthen the evidence that systemic blood pressure fundamentally influences ocular circulation and consequently glaucoma progression.