Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study.

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

Five-year cumulative incidence and progression of age-related macular degeneration: results from the German population-based Gutenberg Health Study (GHS).

PURPOSE: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age. The baseline examination, including fundus photography, was conducted between 2007 and 2012, and the 5-year follow-up examination was performed between 2012 and 2017. AMD grading of fundus photographs was performed according to the Rotterdam Eye Study classification. The 5-year cumulative incidence and progression of AMD were calculated. Poisson regression analysis was conducted to investigate factors associated with the cumulative incidence and progression of AMD. RESULTS: Six-thousand-eight-hundred-eighty-eight participants (49.8%, n = 3427 female) were included in the analysis. AMD prevalence was 8.5% [95% CI: 7.9-9.2%] at baseline and 10.3% [95% CI: 9.6-11.1%] at follow-up. The cumulative 5-year-incidence was 2.0% [1.7-2.4%]. AMD progression within 5 years was seen in 18.1% [95% CI: 15.1-21.5%] of the participants. AMD incidence and AMD progression were associated with higher age, for each 10-year increase in age, the risk of AMD doubles (RR = 2.30), and the risk of progression of the disease is increased by 1.6. while AMD incidence also with pseudophakic status. CONCLUSIONS: In summary, this population-based sample provides substantial epidemiologic data from a large German cohort, including data on progression and cumulative incidence of macular degeneration in younger age groups. AMD progression over 5 years is common in the German population, 18.1% of subjects with AMD showed progression in at least one eye in this time frame and is associated with higher age. Nevertheless, although usually defined to occur over the age of 50, in this cohort AMD occurred in 0.5% and AMD progression occurred in 5.4% of those already affected in the youngest age group before 50 years of age.

[Differential diagnosis of intraorbital masses - a narrative review]. / Differentialdiagnostik intraorbitaler Raumforderungen ­ eine Übersicht.

OBJECTIVE: Intraorbital masses represent a condition that is frequently threatening for the visual system. A rigorous differential diagnosis is essential to promptly initiate appropriate therapy and optimize prognosis. MATERIALS/METHODS: Narrative review of current literature and expert recommendations. For further illustration we describe the case of a 71-year-old male admitted to our department three months after sinus surgery. Postoperative intraorbital hematoma of the right orbit had been treated conservatively with antibiotics/corticosteroids, leading to a near-complete unilateral visual loss. The immediate surgical intervention aimed at decompression of the orbit and the optical nerve. Due to the delay, the intervention could not prevent formation of a lipogranuloma. Inflammatory phases associated with the lipogranuloma are successfully managed by conservative treatment based on multidisciplinary recommendations. RESULTS: In the case reported, delay of surgical therapy acted as a cause of intraorbital lipogranuloma formation. Literature supports our recommendation of immediate surgical intervention in case of acute retrobulbar hematoma. Besides acute conditions, intraorbital masses can be a sign of systemic disease. In every case, a multidisciplinary therapeutic approach is required for adequate management. CONCLUSIONS: Intraorbital masses can occur as a complication of trauma or e.g. sinus surgery. On the other hand they can be a sign of systemic disease. Timely diagnosis and treatment prevents from visual loss. That is why rigorous differential diagnosis is essential for every discipline managing intraorbital lesions.

Posterior segment eye lesions: prevalence and associations with ocular and systemic parameters: results from the Gutenberg Health Study.

BACKGROUND: To estimate the prevalence of posterior segment eye lesions and to identify their ocular and systemic associations within the Gutenberg Health Study (GHS) in Germany. METHODS: Assessment and grading of fundus images as well as physical examination and history taking were performed in the cross-sectional analysis of 15,010 subjects (aged 35-74 years) using standardised procedures to determine the prevalence and associations of various posterior segment eye lesions. RESULTS: Fundus photographs of both eyes were available for 12,782 (85.2%; 50% female) subjects. The prevalence weighted to the region of Mainz and Mainz-Bingen in Germany was for choroidal nevi 2.4%, drusen of the optic nerve head 0.2%, tilted discs 1.5%, chorioretinal scars suggestive of toxoplasmosis 0.2%, retinitis pigmentosa 0.04% and persistent hyaloid artery 0.02%. Choroidal nevi were positively associated with a history of myocardial infarction (OR = 2.7, 95% confidence interval 1.2-6.2, p value = 0.017). Tilted discs were positively associated with increased intraocular pressure (OR = 1.09 per mm Hg (1.02-1.16), p = 0.011) and negatively associated with smoking (OR 0.4 (0.3-0.7), p = 0.0022). Participants with tilted discs had a mean spherical equivalent of - 3.6 dioptres (standard deviation 4.0) compared with - 0.4 dioptres (2.4) to those without. CONCLUSION: Our study is-to the best of our knowledge-the first to determine the prevalence of drusen of optic nerve head among Caucasians, to show a positive association between tilted discs and increased intraocular pressure and questions a possible link between choroidal nevi and myocardial infarction. It also showed that participants with tilted discs had a lower mean spherical equivalent than those without.

Refractive, corneal and ocular residual astigmatism: distribution in a German population and age-dependency - the Gutenberg health study.

PURPOSE: Worldwide, the most frequent cause of visual impairment is uncorrected refractive error. This analysis focused on the distribution and associations of refractive, corneal and ocular residual astigmatism. METHODS: As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in the general population of Germany. A comprehensive ophthalmological examination including refraction, tonometry, and Scheimpflug imaging of the anterior cornea (Pachycam) was performed. In addition to the magnitude and type (with-the-rule, against-the-rule, oblique) of the refractive or corneal astigmatism, we calculated the vector components (J0, J45) of both astigmatisms and calculated the ocular residual astigmatism. We performed multiple quantile regression analysis to evaluate the factors associated with refractive, corneal and ocular residual astigmatisms. RESULTS: A total of 13,558 subjects (49% female) with a mean age of 54.0 years (range 35-74 years) were included in this study. The prevalence of refractive astigmatism (>1.0D) was 13.0% in right eyes and 12.0% in left eyes, and 85% of these subjects wore spectacles. The distribution of refractive astigmatism showed a two-peak distribution with high astigmatism for with-the-rule and against-the-rule astigmatism. The associated factors were corneal curvature, age and sex for the different astigmatisms (p < 0.001). CONCLUSIONS: We analyzed the prevalence of different astigmatisms within a European population. We confirmed a shift with aging from with-the-rule to against-the-rule astigmatism to refractive and corneal astigmatism. Astigmatism has a large impact on visual perception; more than 85% of people with astigmatism over one diopter wore glasses for distance vision.

Prevalence of diabetic retinopathy in screening-detected diabetes mellitus: results from the Gutenberg Health Study (GHS).

AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus may experience an asymptomatic period of hyperglycaemia, and complications may already be present at the time of diagnosis. We aimed to determine the prevalence of diabetic retinopathy in patients with newly diagnosed (screening-detected) type 2 diabetes. METHODS: The Gutenberg Health Study is a population-based study with 15,010 participants aged between 35 and 74 years. We determined the weighted prevalence of diabetic retinopathy by assessing fundus photographs. Screening-detected type 2 diabetes was defined as an HbA1c concentration of 6.5% (47.5 mmol/mol) or more, no medical diagnosis of diabetes and no intake of insulin or oral glucose-lowering agents. RESULTS: Of 14,948 participants, 1377 (9.2%) had diabetes mellitus. Of these, 347 (25.2%) had newly diagnosed type 2 diabetes detected by the screening. Overall, the weighted prevalence of screening-detected type 2 diabetes was 2.1%. Fundus photos were evaluable for 285 (82.1%) participants with newly diagnosed diabetes. The weighted prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13.0%; 12% of participants had a mild non-proliferative diabetic retinopathy and 0.6% had a moderate non-proliferative diabetic retinopathy. Diabetic retinopathy was proliferative in 0.3%. No cases of severe non-proliferative diabetic retinopathy or diabetic maculopathy were found. Thirty (14.9%) of 202 and six (7.2%) of 83 individuals with and without concomitant arterial hypertension, respectively, had diabetic retinopathy (OR 2.54, 95% CI 1.06, 7.14). Visual acuity did not differ between individuals with and without diabetic retinopathy . CONCLUSIONS/INTERPRETATION: In this large European study, the prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13%. Only a very small proportion of participants with detected diabetic retinopathy needed treatment.

PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS: Results From the Population-Based Gutenberg Health Study.

PURPOSE: To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. RESULTS: In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with history of stroke (OR, 6.8; 95% CI, 2.9-16.1; P < 0.001). Myelinated retinal nerve fibers was not associated with age, sex, cardiovascular conditions other than stroke or ocular parameters, such as refraction, visual acuity, intraocular pressure, or central corneal thickness. CONCLUSION: This population-based study provides novel data on the prevalence of MRNF in Western Europe. We report a positive association between history of stroke and MRNF. It adds an additional retinal sign for stroke and calls for further studying of the behavior of oligodendrocytes within cerebrovascular diseases.

Myopia and level of education: results from the Gutenberg Health Study.

PURPOSE: To analyze the association between myopia and educational level in an adult European cohort. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A cohort of the Gutenberg Health Study, including 4658 eligible enrollees between 35 and 74 years of age. METHODS: We applied a standardized protocol entailing a comprehensive questionnaire; thorough ophthalmic, general, cardiovascular, and psychological examinations; and laboratory tests, including genetic analyses. We documented achievement levels in school education and post-school professional education. The spherical equivalent (SE) was determined by noncycloplegic autorefractometry. We fitted mixed linear models including age, gender, and 45 myopia-associated single nucleotide polymorphisms (SNP) as covariates. MAIN OUTCOME MEASURES: Prevalence and magnitude of myopia in association with years spent in school and level of post-school professional education. RESULTS: Individuals who graduated from school after 13 years were more myopic (median, -0.5 diopters [D]; first quartile [Q1]/third quartile [Q3], -2.1/0.3 D) than those who graduated after 10 years (median, -0.2 D; Q1/Q3, -1.3/0.8 D), than those who graduated after 9 years (median, 0.3 D; Q1/Q3, -0.6/1.4 D), and than those who never finished secondary school (median, 0.2 D; Q1/Q3, -0.5/1.8 D; P<0.001, respectively). The same holds true for persons with a university degree (median, -0.6 D; Q1/Q3, -2.3/0.3 D) versus those who finished secondary vocational school (median, 0 D; Q1/Q3, -1.1/0.8 D) or primary vocational school (median, 0 D; Q1/Q3, -0.9/1.1 D) versus persons without any post-school professional qualification (median, 0.6 D; Q1/Q3, -0.4/1.7 D; P<0.001, respectively). Of persons who graduated from school after 13 years, 50.9% were myopic (SE, ≤-0.5 D) versus 41.6%, 27.1%, and 26.9% after 10 years, in those who graduated after 9 years, and in those who never graduated from secondary school, respectively (P<0.001). In university graduates, the proportion of myopic persons was higher (53%) than that of those who graduated from secondary (34.8%) or primary (34.7%) vocational schools and than in those without any professional training (23.9%; P<0.001, respectively). In multivariate analyses: higher school and professional levels of education were associated with a more myopic SE independent of gender. There was a small effect of age and SNPs. CONCLUSIONS: Higher levels of school and post-school professional education are associated with a more myopic refraction. Participants with higher educational achievements more often were myopic than individuals with less education.

Redox mechanisms in autoimmune thyroid eye disease.

Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1ß, IL-6, and transforming growth factor (TGF)-ß. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease.

Background: Thyroid eye disease (TED) involves several pathogenic pathways and a battery of infiltrating mononuclear cells, cytokines, and chemokines in the orbit. Revealing the main molecules, which play a major role in the pathogenesis of TED, will help developing novel treatment strategies. Methods: In a multicenter, single-blind, case-control study, 60 tissue samples were collected during orbital decompression (44 TED patients) or non-TED related oculoplastic (16 controls) surgeries. Formalin-fixation and paraffin embedding preserved orbital tissue. Tissue sections were immunostained with 18 antibodies by the micro-polymer labeling technique. Immunostaining slides were scanned by Panoramic Desk and blindly evaluated by a user-independent viewer software. Results: Marked lymphocyte infiltration was observed in orbital tissue specimens of patients with clinically active TED (n = 22) and to a much lesser extent in inactive cases (n = 22), while it was absent in controls. Increased vascularity was noted in all samples, with orbital congestion in specimens of clinically active TED. Tissue fibrosis was present in TED samples but not in controls. Immunohistochemistry of orbital tissue clearly differentiated between TED and controls, as well as between active and inactive TED. In contrast to controls and with the exception of cluster of differentiation 20 (CD20), 17 out of 18 antibodies were highly expressed in orbital connective tissue of TED patients. Especially, thyrotropin receptor (TSH-R), insulin-like growth factor 1 receptor (IGF-1R), CD40, cluster of differentiation 40 ligand (CD40L), CD3, CD68, interleukin-17A (IL-17A), IL-23A, IL-1ß, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage chemoattractant protein 1 (MCP-1), IL-16, and B cell activating factor (BAFF) were overexpressed in clinically active TED (all p < 0.001). Also, the expression of CD40L, IL-17A, IL-23A, IL-6, IL-1ß, RANTES, and BAFF was very high (TED/control ratio >3), moderate (ratio >2), and low in active (p < 0.001), inactive TED and controls, respectively. The expression of TSH-R, IGF-1R, CD40, CD40L, CD3, CD68, CD20, IL-17A, IL-23A, RANTES, MCP-1, and BAFF positively and significantly correlated with both serum TSH-R stimulatory antibody concentrations and clinical activity scores while it negatively correlated with TED duration. Orbital irradiation decreased TSH-R (p < 0.001) and IGF-1R expression (p = 0.012); in contrast, neither smoking, age, nor gender did impact immunohistochemical staining. Conclusions: Adaptive and cell-mediated immunity, overexpression of TSH-R/IGF-1R and CD40/CD40L are the relevant pathomechanisms in TED. Targeting these key players in the active phase of the disease offers specific and novel treatment approaches.

Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy.

PURPOSE: Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. DESIGN: Cross-sectional trial. PARTICIPANTS: A total of 108 untreated patients with GO. METHODS: Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compared with a TSHR binding inhibitory immunoglobulin (TBII) assay. MAIN OUTCOME MEASURES: Thyroid-stimulating immunoglobulins, activity and severity of GO, diplopia, and TBII. RESULTS: Thyroid-stimulating immunoglobulins were detected in 106 of 108 patients (98%) with GO. All 53 hyperthyroid patients were TSI positive versus 47 patients (89%) who were TBII positive. All 69 patients with active GO were TSI positive, whereas only 58 of 69 patients (84%) were TBII positive. Thyroid-stimulating immunoglobulins correlated with the activity (r=0.83, P < 0.001) and severity (r=0.81, P < 0.001) of GO. All 59 patients with GO with diplopia were TSI positive, and 50 of 59 patients (85%) were TBII positive. Among patients with moderate-to-severe and mild GO, 75 of 75 (100%) and 31 of 33 (94%) were TSI positive compared with TBII positivity in 63 of 75 (84%) and 24 of 33 (73%), respectively. The TSI levels were higher in moderate-to-severe versus mild GO (489%±137% vs. 251%±100%, P < 0.001). Chemosis and GO activity predicted TSI levels alone (P < 0.001, multivariable analysis). The TSI levels were higher in patients with chemosis (527%±131%) than in patients without chemosis (313%±127%, P < 0.001). CONCLUSIONS: Thyroid-stimulating immunoglobulins show more significant association with clinical features of GO than TBII and may be regarded as functional biomarkers for GO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Perioperative pupil size in low-energy femtosecond laser-assisted cataract surgery.

PURPOSE: To assess potential changes in pupil size during femtosecond laser-assisted cataract surgery (FLACS) using a low-energy laser system. METHODS: The pupil sizes of eyes undergoing FLACS were measured using the Ziemer LDV Z8 by extracting images from the laser software after each of the following steps: application of suction, lens fragmentation, and capsulotomy. Furthermore, the pupil diameters were measured based on preoperative surgical microscope images and after releasing the suction. Paired t-test and the two one-sided tests (TOST) procedure were used for statistical analyses. The horizontal and vertical pupil diameters were compared in each of the steps with preoperative values. RESULTS: Data were available for 52 eyes (52 patients, mean age 73.4 years, range 51-87 years). The equivalence between mean preoperative pupil size and status immediately after femtosecond laser treatment was confirmed (p<0.001; 95% confidence interval [-0.0637, 0.0287] for horizontal and p<0.001; 95% CI [-0.0158, 0.0859] for vertical diameter). There was statistically significant horizontal and vertical enlargement of pupil diameters between 0.15 and 0.24 mm during the laser treatment steps as compared with preoperative values (all p values <0.001). CONCLUSIONS: No progressive pupil narrowing was observed using low-energy FLACS. Although a suction-induced, slight increase in pupil area became apparent, this effect was completely reversible after removing the laser interface.

[Diagnostics of benign and malignant tumors of the orbit]. / Diagnostik von benignen und malignen Tumoren der Orbita.

BACKGROUND: Orbital space-occupying lesions can have a significant impact on the quality of life. Depending on the dignity and etiology of the mass, they can even represent a life-threatening process, which must be timely treated in an interdisciplinary cooperation. OBJECTIVE: To achieve a comprehensive overview about the diagnostics and frequency of malignant and benign masses of the orbit. MATERIAL AND METHODS: A literature search was carried out in PubMed and Google scholar. RESULTS AND DISCUSSION: Clinically, orbital lesions can show symptoms, such as exophthalmos with an increase in the vertical lid fissure, visual impairment and motility dysfunction with diplopia. Depending on the extent, an exposure keratopathy can occur due to failure to close the eyelids. For the diagnostics several tests should be carried out. Following a thorough anamnesis and clinical examination, these should include a blood sample to test for various parameters, an ultrasound examination with subsequent computed tomography (CT) in cases of bone involvement or thin slice magnetic resonance imaging (MRI) of the orbit for assessment of soft tissues. In adults an endocrine orbitopathy is the most frequent cause of an inflammatory orbital process, where lymphomas are the most frequent entity among malignant tumors and vascular space-occupying lesions are the most frequent benign tumors. In children the most frequent benign masses are dermoid cysts and rhabdomyosarcoma is the most frequent primary malignant orbital tumor. The multimodal interdisciplinary treatment can include surgical excision and adjuvant radiotherapy or chemotherapy, depending on the entity.

[Treatment and management of orbital tumors]. / Therapie und Versorgung von orbitalen Tumoren.

BACKGROUND: There are various options for the conservative treatment of the most frequent orbital tumors. These can delay, complement or be superior to the surgical approach, which is often prone to complications. OBJECTIVE: This article gives a summary of the possible treatment options for the most common orbital tumors in childhood and adulthood. METHODS: A literature search was carried out and the possible treatment pathways are presented. RESULTS: 1. Frequent orbital tumors in childhood: a systemic treatment with noncardioselective beta blockers is the primary treatment for capillary orbital hemangiomas. In cases of no response, steroids, interferon alpha or cyclophosphamide are treatment options. Observation is a possible option for smaller dermoid cysts, in cases of progression excision can become necessary. Symptomatic optic nerve gliomas can also be observed and in cases of progression treated with chemotherapy, mTOR/MEK inhibitors or radiotherapy (children > 5 years). Rhabdomyosarcomas are biopsied and subsequently treated by radiotherapy and chemotherapy. 2. Frequent orbital tumors in adulthood: asymptomatic cases of cavernous hemangiomas of the orbit can just be observed. Symptomatic hemangiomas can be surgically excised or treated with radiotherapy. For meningiomas of the optic nerve sheath radiotherapy is a very effective treatment. Surgical excision should be reserved for cases with no prognosis of visual acuity. There is also the option to treat with antiprogesterone. Orbital lymphomas with purely orbital involvement can be treated with radiotherapy, chemotherapy or the application of rituximab. CONCLUSION: There are now very effective conservative treatment options for many orbital tumors. In some cases a surgical procedure can be avoided and a good visual function can be retained.

[Asymmetric dimethylarginine (ADMA) in retinal vein occlusion-Results from the Gutenberg RVO study]. / Asymmetrisches Dimethylarginin (ADMA) bei retinalen Venenverschlüssen ­ Ergebnisse aus der Gutenberg-RVO-Studie.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is considered an independent cardiovascular risk factor (cvRF) and thus represents a potential new biomarker for retinal vein occlusion (RVO). METHODS: Overall, 92 patients with RVO and the same number of matched controls were included in the Gutenberg RVO study. All patients underwent a standardized examination for cvRF at the study center of the population-based Gutenberg health study (GHS) as well as ophthalmological examinations and intensive laboratory tests. This article presents a substudy of patients (≤65 years old) and the controls in whom ADMA was additionally determined by high performance liquid chromatography (HPLC) at baseline and 4-6 weeks later. RESULTS: Out of 44 patients with RVO 22 had central retinal vein occlusion (CRVO), 15 had branch retinal vein occlusion (BRVO) and 7 had hemiretinal vein occlusion (hemi-RVO). The ADMA levels were 0.383 ± 0.094 µM (mean ± standard deviation) in RVO patients at baseline and 0.380 ± 0.093 µM (p = 0.514, initial vs. follow-up) after the follow-up period versus 0.360 ± 0.077 µM (p = 0.175, controls vs. RVO) in controls (n = 44). Arterial hypertension was the most prevalent risk factor in 22 (50%) of the patients and in 11 (25%) of the controls (odds ratio, OR 2.77, 95% confidence interval, CI 0.97-7.95; p = 0.058). The ADMA values above the 95th percentile (>0.530 µM) were detected in 4 patients with RVO (9.1%) but not in any of the controls (p = 0.041, RVO vs. controls). CONCLUSION: Hypertension is the most important risk factor for RVO. Due to the high number of hypertensive patients in the cohort, the relevance of ADMA as an independent risk factor could neither be confirmed nor disproved.

[Visual acuity in German preschool children-results of a cross-sectional study]. / Wie gut sehen unsere ABC-Schützen?

BACKGROUND: Within the framework of the German pediatric screening examinations, the checks include visual functions. There is no ophthalmological screening examination in childhood in Germany. This study investigated whether participation in the pediatric screening examinations U8 (at the end of the fourth year of life) and U9 (at the beginning of the sixth year of life) is associated with the results of visual acuity, which are compiled at the school entry examinations (SEU). METHODS: This study evaluated data of the SEU for school the enrollment years 2009/2010-2014/2015 of the State of Rhineland-Palatinate. In these years visual acuity was assessed using the Rodenstock visual testing device (E-hooks; Rodenstock intruments GmbH, Ottobrunn, Deutschland) wearing glasses if present. The association between participation in the U8 and U9 screening examinations and the presence of unilateral and bilateral visual acuity <0.7 was investigated using multiple logistic regression adjusted for important disturbance variables. RESULTS: Data from 189,704 children (91,041 girls, 98,663 boys) from 35 out of 36 districts were included. A visual acuity <0.7 was measured in 8416 (4.4%) children and in both eyes in 4345 (2.3%) children. The participation rates in the U8 and U9 were 93.9% and 93.3%, respectively. There was a negative association between participation in the U8 and U9 and a unilateral or bilateral SEU visual acuity <0.7 (adjusted odds ratio, OR 0.68, 95% confidence interval, CI 0.61-0.75; p < 0.01, N = 124,467/adjusted OR 0.57, 95% CI 0.51-0.65; p < 0.01, N = 121,496). CONCLUSION: The proportion of children with visual acuity <0.7 at the SEU was high. Children who were examined in the U8 and U9 had a better chance for a good visual acuity in the school entry examination.

[Implementation of a digital semester for ophthalmology during the COVID-19 pandemic]. / Umsetzung eines digitalen Semesters Augenheilkunde während der COVID-19-Pandemie.

BACKGROUND: The first wave of the COVID-19 pandemic posed great challenges for teachers and students, as teaching had to take place despite the restriction of classroom teaching. For attendance lessons and events with patient contact alternatives had to be arranged at short notice between mid-March and the beginning of the semester in mid-April. OBJECTIVE: Description of the concept and implementation in the student teaching at the Department of Ophthalmology of the University Medical Center Mainz in complete digital form in spring 2020. PRESENTATION OF CONCEPT: Lectures, examination course and practical training in ophthalmology take place in the 5th and 6th semester of the study of human medicine. The basis of the new concept were the former course curricula. Implemented concepts included a complete revision and implementation of lectures as video podcasts, examination videos, online examination conferences, interactive patient cases, narrated videos of surgery, anamnesis videos of patients and the design of the virtual patient room, a live online practice with presentation and examination of patients including transmission of the slit-lamp image to reproduce anterior and posterior segment examination. An evaluation showed a very positive reception of the new concept by students. DISCUSSION: Within a tight timeframe of 4 weeks a complete revision of the ophthalmology course was achieved. The implementation was time-consuming, with the largest share in the media production of examination videos, interactive patient cases and video podcasts of the lectures. We consider a reduction of classroom teaching for parts of the learning objectives that can be represented by such videos to be possibly useful. An independent digital appropriation of such content may enable a more productive learning environment in face-to-face teaching.

Birth Weight and Diabetic Retinopathy: Results From the Population-Based Gutenberg Health Study (GHS).

PURPOSE: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population. METHODS: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: <2500 g; normal: 2500-4000 g; high:>4000 g). Logistic regression analysis was conducted as uni- and multivariable analysis with adjustment for age and sex. Effect mediators were separately investigated. RESULTS: A total of 1,124 GHS participants (7.5% of the cohort) had diabetes at study entry. Of these, 402 subjects (35.8%) had gradable fundus photographs, reported BW data and were included into this study. Overall, 91/402 subjects (23%) had DR. With regard to BW groups, DR was descriptively more frequent in subjects with low (28.1% [95%-CI: 14.4-47.0%; n = 32]) and high BW (30.8% [95%-CI: 19.1-45.3%; n = 52]) compared to normal BW (20.8% [95%-CI: 16.5-25.7%; n = 318]). Both high and low BW were associated with DR in multivariable analysis (high: OR = 1.68, p = .037; low: OR = 1.81, p = .05). The BW effect was mediated by duration of diabetes in both BW groups and by arterial hypertension in the low BW group. CONCLUSION: Low and high BW in persons with diabetes is related to higher risk of diabetic retinopathy. Longer duration of diabetes and higher prevalence of arterial hypertension are factors in these subjects explaining the elevated risk.