Katharina A. Ponto

Quality of Life in a German Graves Orbitopathy Population

PURPOSE To evaluate the validity and responsiveness of a German-language version of the disease-specific Graves orbitopathy quality-of-life questionnaire (GO-QOL). DESIGN Prospective cross-sectional study. METHODS At a multidisciplinary university orbital center, 310 consecutive unselected Graves orbitopathy outpatients answered the GO-QOL before undergoing complete ophthalmic and endocrine assessment. The main outcome measures were the GO-QOL and its 2 subscales, Visual Functioning and Appearance. RESULTS The QOL scores for the subscales Visual Functioning and Appearance were (mean ± SE) 72.5 ± 1.4 and 71.3 ± 1.5, respectively. Visual Functioning and Appearance were higher in mild (82.2 ± 2.2 and 86.0 ± 17.6) than in moderate to severe (66.6 ± 1.8, p < .001, 95% CI 15.6-2.9 and 65.5 ± 25.5, P < .001, 95% CI 15.1-26.0) and in sight-threatening Graves orbitopathy (41.9 ± 9.9, P < .001, 95% CI 25.4-55.3 and 58.5 ± 9.0, P < .001, 95% CI 15.0-39.4). Visual Functioning and Appearance were also lower in active (63.3 ± 2.2 and 64.5 ± 2.2) than in inactive stages (77.0 ± 1.9; P < .001, 95% CI 7.9-19.3 and 78.3 ± 1.8, P < .001, 95% CI 8.2-19.2). Visual Functioning was 81.6 ± 1.8 in patients without and 62.4 ± 2.0 in patients with diplopia (P < .001, 95% CI 13.8-24.6). Appearance was lower in those receiving psychotherapy (64.7 ± 3.2) than in those without psychotherapy (74.6 ± 1.6, P = .005, 95% CI 3.0-16.7). Significant ceiling effects (≥15% at the highest value of the subscale) were observed for Appearance in 59 patients (19%) and for Visual Functioning in 85 patients (27%). CONCLUSION The German-language version of the GO-QOL shows evidence of validity in Graves orbitopathy and it usefully complements ophthalmic assessment in these patients.

Proteomics Differentiate Between Thyroid-Associated Orbitopathy and Dry Eye Syndrome

PURPOSE In patients with thyroid-associated orbitopathy (TAO), the dry eye syndrome occurs frequently, and symptoms and signs of both disorders overlap making early and accurate differential diagnosis difficult. A differentiation via specific markers is warranted. METHODS Tear fluid samples of 120 subjects with TAO, TAO + dry eye, dry eye, and controls were collected. The samples were measured using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were tested with antibody microarrays. RESULTS Proteomics identified deregulated proteins in TAO and dry eye. Compared with dry eye, proline-rich protein 1 (PROL1, P = 0.002); uridine diphosphate (UDP)-glucose-dehydrogenase (UGDH, P = 0.017); calgranulin A (S10A8, P < 0.0001); transcription-activator BRG1 (SMCA4, P < 0.0001); annexin A1 (P = 0.007); cystatin (P = 0.009); heat shock protein 27 (P = 0.03); and galectin (P = 0.04) were markedly downregulated in TAO. Compared with healthy controls, PROL1 (P < 0.05.); proline-rich protein 4 (PRP4, P < 0.05), S10A8 (P = 0.004) and SMCA4 (P = 0.002) were downregulated in TAO. In contrast, the proteins midasin and POTE-ankyrin-domain family-member I were upregulated in TAO versus healthy controls (P < 0.05). Protein dysregulation was associated with inflammatory response and cell death. Antibody microarray confirmed significant changes of PRP4, PROL1, and UGDH between TAO and dry eye or healthy controls (P < 0.01). The presence of these three proteins was negatively correlated with smoking (P < 0.05). CONCLUSIONS Proteomics of tear fluid demonstrated an upregulation of inflammatory proteins versus a downregulation of protective proteins in TAO, and a significantly different protein panel in TAO versus dry eye and/or controls. The spectrum of inflammatory and protective proteins might be a useful indicator for disease activity and ocular surface disease in patients with TAO.

Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study

Objective Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany. Research Design and Methods The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases. Results Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955–0.992]; p = 0.006) arterial hypertension (1.90 [1.190–3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504–7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068–1.114]; p<0.0001 and 1.18 [1.137–1.222]; p<0.0001, respectively). Conclusions Our calculations suggest that more than a quarter-million persons have vision-threatening diabetic retinal disease in Germany. Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus.

Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study

To determine the age‐ and sex‐specific prevalence and determinants of retinal vein occlusions (RVOs) in a large population‐based German cohort.

Dose of intravenous steroids and therapy outcome in Graves’ orbitopathy

Background and aim: Several trials have proved the efficacy of intravenous (IV) steroids in Graves’ orbitopathy (GO). However, the impact of administered dose and therapy schedule has not been assessed yet. Subjects and methods: Nine randomized and 14 non-randomized controlled trials of IV steroids in GO were evaluated according to the applied single and cumulative doses with respect to outcome, efficacy on clinically relevant issues and adverse events. Results: High single (1 g per day) and cumulative (>6 g) doses of IV steroids are superior to lower single (0.5 g/d) and cumulative (<5 g) doses with respect to therapy response (84 vs 75%; p=0.034 and 83 vs 77%; ns, respectively), improvement of eye symptoms (87 vs 75%, p=0.052 and 85 vs 71%; ns, respectively) and disappearance of diplopia (32 vs 27%; ns and 48 vs 27%; p=0.08, respectively). Decrease of both clinical activity score (3 vs 2.5 points and 2.5 vs 3, ns) as well as proptosis (−1.4 vs −1.2 mm, ns and 1.5 vs 1.2, ns) are similar in both groups. However, high single and/or cumulative doses are accompanied with a 2-fold higher rate of adverse events (56 vs 28%; p<0.001 and 52 vs 33%; p=0.034, respectively). Conclusions: Tailoring the IV steroid dose to severity of GO can be concluded and implies that a prospective randomized trial comparing different doses of IV steroids in active/severe GO is keenly warranted.

Ophthalmologische Aspekte der Gutenberg Gesundheitsstudie

The Gutenberg Health Study (GHS) is a prospective, single center, population-based cohort study. It is an interdisciplinary project for investigation of ocular, cardiovascular, psychosomatic and immune diseases in the population of the City of Mainz and the district of Mainz-Bingen in central Germany. The main goals of the ophthalmological branch of GHS are determination of the prevalence and incidence of major ocular risk factors and diseases, exploring the genetic determinants and assessing complex interdisciplinary associations. The study cohort includes 15,010 participants aged between 35 and 74 years at the time of inclusion. After completing the baseline investigations the 5-year follow-up of the whole study cohort started in April 2012. The GHS is the most extensive data set of major ophthalmological conditions and risk factors in Germany and will help researchers in understanding complex medical associations.

Myopia and Cognitive Performance: Results From the Gutenberg Health Study.

Purpose To analyze the association between myopia and cognitive performance. Methods A cohort of the population-based Gutenberg Health Study included 3819 eligible enrollees between 40 and 79 years. We used the Tower of London (TOL) test to assess cognitive performance. Myopia was defined as a spherical equivalent (SE) ≤ -0.5 diopters (D) via noncycloplegic autorefractometry. We conducted linear mixed models with the SE as the dependent variable and the age, sex, duration of education, and TOL score as covariates. Results Complete data were available for 3452 participants (90.4%). The mean TOL score was 14.0 ± 3.9 in the myopes versus 12.9 ± 4.0 in the nonmyopes (P < 0.001). The mean TOL score increased with the magnitude of myopia: it was 13.9 ± 3.9 in low (less than -3 D); 14.2 ± 3.7 in moderate (between -3 and -6 D); and 14.6 ± 3.5 in high myopia (-6 D and greater; P < 0.001). Both the duration of education and cognitive performance were correlated with the magnitude of myopia (r = -0.21, P < 0.001 and r = -0.15, P < 0.001, respectively). In a linear mixed model, the duration of education significantly predicted myopia (β = -0.14; t = -7.55; P < 0.001), whereas cognitive performance did not (β = -0.017; t = -1.26; P = 0.207). There was a significant effect of age on the SE (β = 0.049; t = 9.89; P < 0.001). Conclusions When regarded separately, cognitive performance is linked to myopia. However, duration of education, which may be directly related to the risk factors for myopia, is more directly and strongly related to myopia than is cognitive performance. Cognitive ability may be associated with myopia primarily through its impact on level of education.

Prevalence, Phenotype, and Psychosocial Well-Being in Euthyroid/Hypothyroid Thyroid-Associated Orbitopathy.

BACKGROUND At the onset of thyroid-associated orbitopathy (TAO), most patients are hyperthyroid, while scarce data are available on euthyroid/hypothyroid TAO. The aim of this study was to assess the prevalence, phenotype, and psychosocial burden of patients with initially euthyroid/hypothyroid TAO. METHODS The medical records of 461 consecutive and unselected patients with TAO followed at a specialized joint thyroid-eye clinic were analyzed within this retrospective cross-sectional study. Main outcome measures were the prevalence of initially eu- or hypothyroid TAO as well as ophthalmic signs and symptoms, disease-specific quality of life (QoL), work impairment, and rate of psychotherapy in initially eu-/hypothyroid versus hyperthyroid TAO. RESULTS The prevalences of eu-/hypothyroid and hyperthyroid TAO were 4.3% (n=20; [confidence interval, CI, 2.6-6.3]) and 95.7% (n=441; [9.37-9.74]), respectively. In 12 patients (2.6% [CI 1.3-4.3]), Hashimotos thyroiditis was present and in 8 (1.7% [CI 0.7-3.0]) no thyroid disease was noted at the time of inclusion. One (0.05%) patient with eu-/hypothyroid TAO and 172 (39%) with hyperthyroid TAO had clinically active TAO (p=0.001). In eu-/hypothyroid versus hyperthyroid patients, 14 (70%) versus 135 (30.6%) had a mild TAO, 6 (30%) versus 183 (64.2%) a moderate-to-severe TAO, and 0 versus 23 (5.4%) had a sight-threatening TAO (p<0.001). TAO was asymmetric in 4 (20%) eu-/hypothyroid and in 27 (6.1%) hyperthyroid patients (p=0.038). Only 5.3% versus 30.2% and 10.5% versus 44.1% of patients with eu-/hypothyroid and hyperthyroid TAO, respectively, were on sick leave (p=0.003) or work disabled (p=0.018). QoL was less impaired in eu-/hypothyroid versus hyperthyroid TAO (median visual functioning and appearance scores: 100 versus 75; p<0.001 and 81.25 versus 75; p=0.315). Of patients with eu-/hypothyroid and hyperthyroid TAO, 15% and 20.2% had psychotherapy respectively (p=0.409). Eu-/hypothyroid TAO was positively (odds ratio 7.05, p=0.060) and negatively (odds ratio: 0.09, p=0.026) associated with a unilateral involvement and thyrotropin-receptor autoantibodies respectively. CONCLUSIONS Compared with hyperthyroid TAO, QoL and working ability are less impaired in eu-/hypothyroid TAO with an often asymmetric and less severe clinical phenotype.

[Ophthalmological aspects of the Gutenberg Health Study (GHS): an interdisciplinary prospective population-based cohort study].

The Gutenberg Health Study (GHS) is a prospective, single center, population-based cohort study. It is an interdisciplinary project for investigation of ocular, cardiovascular, psychosomatic and immune diseases in the population of the City of Mainz and the district of Mainz-Bingen in central Germany. The main goals of the ophthalmological branch of GHS are determination of the prevalence and incidence of major ocular risk factors and diseases, exploring the genetic determinants and assessing complex interdisciplinary associations. The study cohort includes 15,010 participants aged between 35 and 74 years at the time of inclusion. After completing the baseline investigations the 5-year follow-up of the whole study cohort started in April 2012. The GHS is the most extensive data set of major ophthalmological conditions and risk factors in Germany and will help researchers in understanding complex medical associations.

Endokrine Orbitopathie – aktuelle Diagnostik und Therapie*

KasuistikEine 41-jährige Patientin stellte sich ambulant wegen Schlafproblemen, Haarausfall, brennender, roter Augen und Doppelbildern im Aufblick vor. Die Patientin sei außerdem wegen ihres starren Blicks und der neuerdings sehr geschwollenen Lider angesprochen worden. Die Laborwerte zeigten eine manifeste Hyperthyreose mit einem TSH (thyroideastimulierendes Hormon) < 0,01 mU/l (Normwert 0,4–4,0 mU/l), einem fT3 (freies Trijodthyronin) von 11 pg/ml (1,7–3,7 pg/ml) und einem fT4 (freies Tetrajodthyronin) von 14 ng/dl (0,7–1,5 ng/dl)) mit hohen TSH-Rezeptor-Antikörper-Werten (30,4 IU/l; Normwert < 1,0 IU/l) und bestätigten die Verdachtsdiagnose eines Morbus Basedow mit endokriner Orbitopathie. Bei der klinischen Untersuchung wurden Aktivitätszeichen (Lidschwellung, Bindehautrötung und Chemosis) nachgewiesen, der Befund wurde als „schwer“ klassifiziert. Nach Vorstellung der Patientin in einer interdisziplinären Orbitasprechstunde erfolgte zunächst eine thyreostatische Therapie (Thiamazol 20 mg/Tag), und die Patientin wurde zur dringenden Aufgabe des Rauchens angehalten. Nach Erreichen einer peripheren Euthyreose wurde eine intravenöse Steroidtherapie (wöchentlich 250 mg Methylprednisolon i.v. über 12 Wochen) initiiert. Unter der immunsuppressiven Therapie und der Nikotinabstinenz war die Entzündung der Augen rückläufig. Bei klinischer Inaktivität mit persistierendem Exophthalmus wurde 6 Monate später eine knöcherne Entlastungsoperation durchgeführt. Die Doppelbilder bestanden nur noch bei extremem Aufblick, so dass von einer operativen Schielkorrektur abgesehen wurde.