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.

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.

Association between cardiorespiratory fitness and handgrip strength with age-related macular degeneration: a population-based study.

AIM: To assess whether cardiorespiratory fitness (CRF) and handgrip strength, two objective markers of physical fitness, are associated with age-related macular degeneration (AMD). METHODS: We analysed cross-sectional data from the population-based Study of Health in Pomerania (2008-2012) including 1173 adult men and women aged 20-79 years. Fundus photography of the central retina was recorded with a non-mydriatic camera, and images were graded according to an established clinical AMD classification scale by an experienced reader. CRF was measured using peak oxygen uptake (peakVO2), oxygen uptake at the anaerobic threshold (VO2@AT), and maximum power output (Wmax) from standardised cardiopulmonary exercise testing on a bicycle ergometer according to a modified Jones protocol. Handgrip strength was assessed using a handheld dynamometer. Adjusted prevalence ratios (PR) for the associations of peakVO2, VO2@AT, Wmax and handgrip strength with AMD were derived from multivariable Poisson regression models. RESULTS: PeakVO2, VO2@AT, Wmax and handgrip strength were not associated with AMD. Adjusted PR for AMD associated with a 1-SD increment in peakVO2, VO2@AT, Wmax and handgrip strength were 1.05 (95% CI 0.82 to 1.34), 0.96 (95% CI 0.78 to 1.18), 1.10 (95% CI 0.86 to 1.41) and 1.01 (95% CI 0.79 to 1.30), respectively. These associations were not modified by age, sex, smoking, body mass index and diabetes. Estimates in sensitivity analysis for confounding, selection bias and missing data were similar. CONCLUSION: In our study, CRF and handgrip strength were not associated with AMD. Nevertheless, longitudinal studies with bigger sample sizes are needed to furtherly examine these associations.

[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.

[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.

[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.

High serum thyrotropin levels are associated with retinal arteriolar narrowing in the general population.

BACKGROUND: Recent studies have shown associations of hypothyroidism with arterial blood pressure, atherosclerosis, and inflammation. Based on these pathways, there might also be an association between hypothyroidism and retinal arteriolar narrowing (RAN), a marker of microvascular damage from hypertension, atherosclerosis, and inflammation. Against this background, the aim of this study was to investigate the putative association between serum thyrotropin (TSH) levels and RAN defined by arterio-venous ratio (AVR) from static vessel analysis. METHODS: We used data from 3189 individuals from the second population-based cohort of the Study of Health in Pomerania (SHIP-TREND-0). Thyroid function was defined according to serum TSH and serum diiodothyronine (3,5-T2) levels. Low and high serum TSH levels were defined by the cutoffs 0.3 mIU/L and 3.0 mIU/L. Fundus photography of the central retina was recorded with a nonmydriatic camera, and images were evaluated by one experienced reader. An AVR <0.8 was defined as decreased. Serum TSH levels, low and high TSH, and serum 3,5-T2 levels were associated with AVR by linear regression and with AVR <0.8 by Poisson regression, both adjusted for age, sex, cigarette smoking, alcohol consumption, and intake of beta-blockers. RESULTS: Serum TSH levels were significantly associated with AVR (ß=-0.028 [CI -0.049 to -0.007]; p=0.009) and with a decreased AVR <0.8 (relative risk=2.05 [CI 1.13-3.73]; p=0.019). Individuals with high TSH had a 1.43 higher risk for a decreased AVR ([CI 1.04-1.96]; p=0.027) than individuals with serum TSH levels within the reference range. Serum 3,5-T2 levels were also associated with a decreased AVR (relative risk for an increase of 1 nM=0.45 [CI 0.23-0.87]; p=0.017). CONCLUSIONS: Our results substantiate evidence for an association between hypothyroidism and RAN. Potential mechanisms explaining this association are long-term hypertension, atherosclerotic processes, and inflammation.

Effect of different artificial tears against desiccation in cultured human epithelial cells.

BACKGROUND: A large number of artificial tears is widely used to treat dry eye symptoms. To test the efficacy of these drugs independent of individual parameters in vitro models are required. As described previously, we employed a reproducible in vitro cell culture system to evaluate the desiccation protection capability of some artificial tears. In THE PRESENT PAPER DATA IS PRESENTED OF ANOTHER SET OF PHARMACEUTICAL AGENTS. MATERIAL/METHODS: Conjunctival epithelial cell line Chang 1-5c-4 (series 1) and the corneal cell line 2.040 pRSV-T (series 2) were cultured under standard conditions. Confluent cells were wetted for 20 min with artificial tears (Arufil Uno, Arufil, Lacrimal, Lacophthal sine, Siccaprotect, Tears Again, Vidisept EDO, Vistil, Wet Comod) or PBS as a control. After exposure to a constant air flow for 0, 15, 30 and 45 minutes respectively, cells were incubated with the vital dye alamarBlue. Subsequently, absorption of the oxidised form of the dye was assessed using an ELISA-Reader. RESULTS: Cell best survival rates in series 1 after 15 min were found for Lacrimal (0.89), Wet Comod (0.84) compared to PBS (0.66) and in series 2 for Vidisept EDO (0.57) and Lacrimal (0.56) compared to PBS (0.01). After 45 min highest survival was seen in series 1 for Lacrimal (0.46) and Lacophthal sine (0.36) compared to PBS (0.33) and in series 2 for Lacrimal (-0.06) and Arufil (-0.16) compared to PBS (-0.23). CONCLUSIONS: Both cell lines tested showed different susceptibility towards desiccation and the artificial tears showed differences in preventing cells from desiccation.

Laser scanning confocal microscopy for conjunctival epithelium imaging.

BACKGROUND: Conjunctival disorders may adversely affect tear film and promote/induce the development of sicca syndrome (also known as Sjögren's syndrome). The basic diagnostics of sicca syndrome are slit lamp examination and functional tests (such as the Schirmer test, break-up time, or fluorescein/rose bengal staining). However, morphological analysis requires time and effort, both in terms of technical equipment and labor, and the results are not available immediately. In contrast, when using laser scanning confocal microscopy (LSCM), the anatomy and morphology of the conjunctival epithelium may be evaluated in vivo during the clinical examination. MATERIAL AND METHODS: We examined the conjunctival epithelium of 23 subjects with healthy eyes using LSCM. We compared intraindividual morphological patterns of normal conjunctival epithelium derived from the Heidelberg Retina Tomograph II - Rostock Cornea Module (HRTII-RCM) with those from impression cytology. All examinations were performed on the conjunctiva bulbi at the 12 o'clock position, 2 mm from the limbus corneae. RESULTS: LSCM and impression cytology examine the conjunctival epithelium from identical perspectives. This facilitates an intraindividual comparison of morphological patterns. In addition, artifact detection and the mapping of light/dark pattern recognition of the LSCM to the microscopy of the impression cytology were reliable. LSCM allows in vivo discrimination of non-secretory from secretory cells in conjunctival epithelium. Non-secretory epithelium shows dark, light and bright cytoplasm of epithelial cells on LSCM, in contrast to impression cytology. Nucleoplasmic ratio ranged from 1:1 to 1:4. Shape, size and interior structure were reliable criteria to distinguish goblet cells from non-secretory cells. The interior structure of the goblet cells showed dark or highly reflective bright homogeneous textures. CONCLUSION: LSCM is a feasible method for examining the morphology of conjunctival epithelium using non-invasive in vivo imaging. Morphological criteria for squamous metaplasia of the conjunctiva in sicca syndrome are already known from cytology, and can be used in almost the same manner in LSCM. The separation of epithelial microcysts from small goblet cells is difficult with LSCM. Finally, the clinical application of LSCM in the staging of sicca syndrome has to be evaluated in future studies.

The case of a 1-year-old girl with hereditary hyperferritinemia cataract syndrome.

Hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by high serum ferritin levels in the absence of iron overload accompanied by early onset of bilateral cataracts. The authors report the case of HHCS in a 1-year-old girl in a family of German origin. Routine blood examination revealed serum ferritin levels up to 2530 microg/L. Slit-lamp examination showed bilateral cataracts. HHCS should be considered in cases of high serum ferritin level and bilateral cataracts, which can even occur in pediatric patients. A liver biopsy and bone marrow aspiration are unnecessary diagnostic procedures in cases of HHCS and repeated phlebotomies are harmful.

Lubricating agents differ in their protection of cultured human epithelial cells against desiccation.

BACKGROUND: In dry eye, as a disease of the ocular surface, the instillation of artificial tears should compensate for the deficit in wetting and protect the mucosa against drying. MATERIAL/METHODS: The desiccation protection of different pharmacological substances was tested using the conjunctival epithelial cell line Chang 1-5c-4 (series 1) and the corneal cell line 2.040 pRSV-T (series 2). On confluent cell growth the cultures were wetted for 20 min with various preservative-free preparations of artificial tears The cell cultures were exposed to a constant air flow for 0, 15, 30 and 45 minutes. Cells were incubated with the vital dye Alamar Blue and subsequently absorption of the oxidised form of the dye was measured using an ELISA-Reader. RESULTS: Cell survival rates in series 1 after 0, 15, 30, 45 min were (1.02;0.81;0.35;0.32) for Artelac EDO, (0.82;0.69; 0.63;0.54) for Vidisic EDO, (0.77;0.80;0.67;0.70) for Vidisic Fluid EDO, (0.76;0.70;0.36; 0.34) for Acuolens, (0.97;0.46;0.35;0.33) for Viscofresh, (0.88;0.85;0.37; 0.33) for Hyal Drops SDU, (0.71;0.44;0.34;0.33) for PBS and in series 2 (1.03;0.84;-0.21;-0.20) for Artelac EDO, (0.89;0.92;0.93;0.86) for Vidisic EDO, (0.96;0.88;0.85;0.85) for Vidisic Fluid EDO, (1.01;0.75;-0.02;-0.03) for Acuolens, (0.98;0.17;-0.22;-0.20) for Viscofresh, (0.97;0.83;0.03;-0.21) for Hyal Drops SDU and (0.96;0.26;-0.24;-0.21) for PBS. Vidisic Fluid EDO and Vidisic EDO showed a significantly better protective effect after a drying period of 30 and 45 min. CONCLUSIONS: The protection capability of pharmacological substances against desiccation can be studied in a standardised cell culture system of human epithelial cell lines. Whether these in vitro results are conferrable to the efficacy of artificial tear drops in vivo has to be evaluated in clinical trials.

Surgical occlusion of the lacrimal drainage system.

BACKGROUND: If a lacrimal plug that successfully improves dry eye symptoms is spontaneously lost or causes unwanted effects other than epiphora, surgical occlusion of the lacrimal drainage system should be considered. Here we review current irreversible and reversible techniques to occlude the lacrimal drainage and describe a new surgical technique, termed 'punctum switch', which has the advantage of being permanent and yet potentially is reversible. MATERIAL AND METHODS: A PubMed search was performed to identify the current literature on surgical occlusion of the puncta and canaliculi for dry eyes. The characteristics of the procedures are described, classifying them as temporary or permanent and their localization being either on the level of the lacrimal puncta or canaliculi. A 'punctum switch' graft involves a superficial excision of a piece of lid margin including the punctum. This graft is then rotated and fixated so that the excised punctum comes to rest lateral to the remaining lacrimal ampulla, which in turn is covered by full-thickness lid margin tissue. RESULTS: Established methods include cauterizing or ligating the puncta or canaliculi as well as everting the medial portion of the lid. Both thermal and surgical techniques show a high rate of reopening. If permanent occlusion is achieved, this however often is irreversible and can only be treated by means of lacrimal bypass surgery. The 'punctum switch' procedure can achieve long-term occlusion of the canalicular system while offering potential reversibility. CONCLUSION: A large variety of surgical techniques to occlude the nasolacrimal drainage system exists. These vary significantly in terms of complexity and reversibility. Surgical occlusion should be used more often in patients with moderate or severe dry eye, which previously responded well to temporary occlusion with plugs.

Age-related differential expression of apoptosis-related genes in conjunctival epithelial cells.

PURPOSE: To investigate whether the expression of apoptosis-related genes in normal conjunctival epithelial cells is age-related (as a prerequisite to assessing whether dysregulation of apoptosis may be involved during degenerative diseases). METHODS: Differential expression of apoptosis-related genes (e.g. apoptosis protease-activating factor 1 [Apaf-1]; caspases [casp] 3, 5, 8 and 9; Bad, Bax, Bcl-2, Bim, c-myc, Bag-1, as well as p53) was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Samples were obtained from impression cytology (IC) specimens taken from 50 healthy subjects. Group A comprised 27 subjects aged 19-32 years and group B included 23 subjects aged 53-84 years. RESULTS: Reverse transcription-PCR revealed the detection of apoptosis-related m-RNAs as follows (group A compared to group B): Apaf-1 0%/0%; Bcl-2 0%/35%; Bim 0%/9%; Bag-1 0%/9%; p53 0%/4%; casp-3 11%/52%; casp-5 59%/48%; casp-8 44%/22%; casp-9 4%/9%; Bax 81%/52%; Bad 96%/56%, and c-myc 89%/96%. CONCLUSION: The data show an age-related expression of apoptosis-related genes such as casp-3, Bad, Bax and Bcl-2 in normal conjunctival cells. These results provide basic information which will help us understand the expression pattern of apoptotic genes during physiological ageing of the conjunctiva and the possible dysregulation of apoptotic genes during acute and chronic diseases such as dry eye disease, allergic conjunctivitis or cicatrizing conjunctivitis.

[Evidence of silicone oil deposits via high resolution ultrasound]. / Nachweis von Silikonöl mittels hochauflösender Sonographie.

BACKGROUND: Using biomicroscopy the evidence of deposits of silicone oil in the anterior segment after vitrectomy is limited. We examined the anterior segment by high resolution ultrasound to verify the possibility to identify silicone oil. MATERIALS AND METHODS: Ten patients treated by vitrectomy with instillation of silicone oil were examined by high resolution ultrasound before and after the removal of silicone oil. The duration of silicone oil tamponade was at least 5 months. A 20-MHz-sectorscanner was used for examination. We compared the findings of ultrasound and biomicroscopy with groups of patients with or without pharmacological mydriasis, blue or brown colour of the iris. RESULTS: The patients treated by vitrectomy and instillation of silicone oil showed small high reflective structures at the endothelium, the anterior front of the iris and in the angle. These highly reflective structures were found more often before, less often after operative extraction of silicone oil and could not be shown in the control groups. Using biomicroscopy we could not see an equivalent to all of the highly reflective structures. CONCLUSIONS: The highly reflective structures we found by ultrasound are probably inclusions in endothelial cells, silicone oil-induced calcifications or free particles of silicone oil. High resolution ultrasound with a 20-MHz-sectorscanner can be used for identifying indication and localising of silicone oil in the anterior segment even if biomicroscopic signs are absent.