Evaluation of a Retinal Projection Laser Eyeware in Patients with Visual Impairment Caused by Corneal Diseases in a Randomized Trial.

PURPOSE: Patients with incurable corneal diseases experience visual impairment (VI) despite having a healthy retina and optic pathway. Low-vision aids (LVAs) can optimize the use of remaining vision through magnification and contrast enhancement, but do not harness the full visual capacity because they rely on the optic media. Therefore, we investigated a novel laser eyewear (LEW) technology that bypasses the anterior segment of the eye. Images captured by an integrated camera are projected directly onto the retina using a low-energy laser. The patient is able to view a full-color video, realized as augmented reality. We aimed to evaluate the efficacy of the LEW to enhance the vision of individuals with corneal diseases. DESIGN: Prospective, randomized, crossover clinical trial. PARTICIPANTS: We examined the retinal projection glasses in 21 patients (25-69 years) with VI (0.7 logarithm of the minimum angle of resolution [logMAR] or worse) resulting from corneal diseases. Patients with comorbidities that impact vision, such as retinal disorders, were excluded. METHODS: Standardized measurements of visual acuity (VA) for near vision (NV) and distance vision (DV) were conducted using ETDRS charts with the respective best correction (BC) and then with LEW. In addition reading speed, vision-related quality of life (QoL) and capacity to carry out daily tasks were assessed at an initial visit and at 2 subsequent visits after a home phase with and without the device. Six weeks after last use of the LEW, an ophthalmologic examination including spectral-domain-OCT or full-field-electroretinography was conducted and compared with baseline findings to evaluate the safety of the device. Four patients participated and completed a subsequent 12-month follow-up phase. MAIN OUTCOME MEASURES: Improvement of VA using the LEW. Secondary objectives included safety, reading speed, QoL, and usability in daily activities. RESULTS: The mean VA in patients with VI was improved by 0.43 logMAR in DV using the LEW compared with BC (P < 0.0001). Using the ×2 magnification mode of the LEW resulted in an average improvement of 0.66 logMAR compared with BC (P < 0.0001). In NV, an increase of 0.47 logMAR was achieved compared with BC (P < 0.0001). Although only 4 of 21 participants were able to read with BC, 17 of 21 participants were able to read with the LEW. Quality of life significantly improved in the 17 participants who completed all visits. CONCLUSIONS: We demonstrated that the retinal projection glasses resulted in enhanced VA for all participants by directly projecting images onto the intact retina. In future, the LEW could represent a new option as an LVA for patients with corneal diseases. No pathological alterations were observed in the safety assessments. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Current Therapeutic Approaches for Graves' Orbitopathy - are Targeted Therapies the Future? / Aktuelle Therapieansätze der endokrinen Orbitopathie ­ sind die zielgerichteten Therapien die Zukunft?

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases.

[Graves' orbitopathy: Current concepts for medical treatment]. / Endokrine Orbitopathie: Aktueller Stand der medikamentösen Therapie.

BACKGROUND: The therapy of severe manifestations of Graves' orbitopathy (GO) is still a challenge and requires good interdisciplinary cooperation. It is especially important to use stage-adapted anti-inflammatory therapy to avoid irreversible damage. MATERIAL AND METHODS: Discussion of the latest results of multicentre randomised therapy studies on anti-inflammatory treatments for Graves' orbitopathy, as well as new therapeutic concepts. RESULTS: Mild cases of GO can be treated with only selenium supplementation and a watchful waiting strategy. In the moderate-to-severe active form of GO, primary therapy consists of i. v. steroids (cumulative 4-5 g) in combination with orbital irradiation in patients with impaired motility. In patients with insufficient therapeutic response after 6 weeks, treatment should be switched to other immunosuppressive agents. In severe sight-threatening disease, bony orbital decompression is usually necessary. As basic research has improved our understanding of the underlying pathophysiology of GO, it has been possible to develop targeted therapies for GO. Teprotumumab, an IGF-1 receptor antibody, was effective in treating GO patients in a phase III trial and should soon be awarded approval for Europe. CONCLUSION: The current therapy concept for Graves' orbitopathy is as follows: first anti-inflammatory therapy then surgical correction of the permanent defects. This may soon be modified, due to the use of targeted therapies.

Proposing a surgical algorithm for graduated orbital decompression in patients with Graves' orbitopathy.

PURPOSE: To determine the outcome after orbital decompression using a graduated technique, adapting the surgical technique according to individual patients' disease characteristics. METHODS: We retrospectively examined the postoperative outcome in patients treated with a graduated balanced orbital decompression regarding reduction of proptosis, new onset diplopia and improvement in visual function. 542 patients (1018 orbits) were treated between 2012 and 2020 and included in the study. Clinical examinations including visual acuity, exophthalmometry (Hertel) and orthoptic evaluation were performed preoperatively and at minimum 6 weeks postoperatively. Mean follow-up was 22.9 weeks. RESULTS: Mean proptosis values have significantly decreased after surgery (p < 0.01). In 83.3% of the patients Hertel measurement normalized (≤ 18 mm) after surgery, New onset diplopia within 20° of primary position occurred in 33.0% of patients, of whom 16.0% had preoperative double vision in secondary gaze. Patients suffering from dysthyroid optic neuropathy (DON) had a significant increase in visual acuity (p < 0.01). CONCLUSION: We demonstrated that individually adapted graduated orbital decompression successfully improves key disease parameters of Graves' orbitopathy with low morbidity.

Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Predicting the Course of Graves' Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay.

The aim of the study was to investigate the use of serial measurements of TSH-receptor autoantibodies (TRAb) with the newest available assay technology to predict the course of Graves' Orbitopathy (GO) during the first 24 months from disease onset. Serial serum samples from patients with GO (103 mild/135 severe) were collected between 2007 and 2017 and retrospectively analyzed. The course of GO were classified into mild/severe 12 months after manifestation (severe: NOSPECS≥5; mild<5). TRAb were measured with automated binding immunoassays (IU/l): TRAb Elecsys (Cobas, Roche), TRAb bridge assay (IMMULITE, Siemens), and a cell-based bioassay (percent of specimen to reference ratio - SRR%) (Thyretain, Quidel). Variable cut off levels of measured TRAb were calculated at specificity of 90% from receiver operator curve (ROC) analysis for several timepoints during the course of GO. To select one: 5-8 months after first GO symptoms, which is the timepoint for usual referals for treatment mild course could be predicted at cut offs of 1.5 IU/l (Elecsys), 0.8 IU/l (Immulite) and 402% SRR (Thyretain) and the risc of severe course has to be anticipated if TRAb are above 11.6 IU/l (Elecsys), 6.5 IU/l (Thyretain), and 714% SRR (Thyretain). The Thyretain bioassay showed the highest diagnostic sensitivity (using the commercial cut off's) over the entire follow up period. TRAb measurements during the 24-month follow up of GO provide added value to the GO clinical activity and severity scores and should be used especially in the event of an unclear decision-taking situation with regard to therapy.

Predicting the Relapse of Hyperthyroidism in Treated Graves' Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies.

The aim of this study was to investigate the potential of the new TSH-receptor antibody (TRAb) assays to predict remission or relapse of hyperthyroidism in patients with Graves' disease (GD) and Graves' orbitopathy (GO). TRAbs were measured retrospectively in sera from a cohort of GD patients with GO (n=117; remission n=38 and relapse n=79-Essen GO biobank) with automated binding immunoassays: TRAb Elecsys (Cobas Roche) and TRAb bridge assay (IMMULITE, Siemens), and the TSAb (thyroid stimulating Ab) cell-based bioassay (Thyretain, Quidel Corp.). To identify relapse risk/remission of hyperthyroidism patients were followed up at least 10 months after the end of antithyroid drug therapy (ATD) therapy. ROC plot analysis was performed to calculate cut-off levels of TRAb and TSAb for prediction of relapse and remission of hyperthyroidism. Cut-off serum levels are provided for timepoints around 3, 6, 10, and 15 months after the beginning of ATD. Repeated measurements of TRAb increase the rate of relapses predictions to 60% (Elecsys), 70% (IMMULITE), and 55% (Thyretain). Patients with remission have consistently TRAb levels below the cut off for relapse in repeated measurements. The cell-based bioassay was the most sensitive - and continued to be positive during follow up [at 15 months: 90% vs. 70% (IMMULITE) and 65% (Elecsys)]. Identification of relapsing hyperthyroidism is possible with automated immunoassays and cell-based bioassay especially with serial TRAb measurements during the course of ATD therapy. Patient who need eye surgery may profit from an early decision towards definitive treatment.

18 F-FDG-PET/MRI in patients with Graves' orbitopathy.

PURPOSE: Currently, therapeutic management of patients with Graves' orbitopathy (GO) relies on clinical assessments and MRI. However, monitoring of inflammation remains difficult since external inflammatory signs do not necessarily represent the orbital disease activity. Therefore, we aimed to evaluate the diagnostic value of 18F-FDG-PET/MRI to assess the inflammation of GO patients. METHODS: Enrolled patients with new onset of GO underwent ophthalmological examinations to evaluate the activity (CAS) and severity of GO (NOSPECS), as well as an 18F-FDG-PET/MRI (Siemens Biograph mMR) with dual time point imaging (immediately post-injection and 60 min p.i.). A subset of PET parameters including maximum standardized uptake value (SUVmax), metabolic target volume (MTV), and total lesion glycolysis (TLG) were obtained separately per eye and per extraocular eye muscle (EOM). EOM thickness was measured on the co-registered MRI. RESULTS: Of 14 enrolled patients, three showed mild, seven moderate-to-severe, and four sight-threatening GO. Patients with severe GO showed statistically significant higher TLG than patients with mild GO (p = 0.02) and higher MTV than patients with mild (p = 0.03) and moderate (p = 0.04) GO. Correlation between NOSPECS on one hand and MTV and TLG on the other was significant (R2 = 0.49-0.61). CONCLUSION: TLG and MTV derived from FDG-PET appear to be good discriminators for severe vs. mild-to-moderate GO and show a significant correlation with NOSPECS. As expected, PET parameters of individual eye muscles were not correlated with associated eye motility, since fibrosis, and not inflammation, is mainly responsible for restricted motility. In conclusion, 18F-FDG-PET/MRI can be used for assessment of GO inflammation.

Risk Factors for New Onset Diplopia After Graduated Orbital Decompression.

PURPOSE: The aim of the study was to identify possible risk factors for new onset diplopia in 20° of primary position (NOD PP) after orbital decompression. A predisposition for NOD has been established for patients with pre-existing diplopia in secondary gaze; therefore, the authors focused on patients without preoperative diplopia. METHODS: Retrospective chart review of patients who underwent balanced orbital decompression between 2012 and 2019 due to Graves orbitopathy at the authors' institution. Exclusion criteria were incomplete clinical data set, revision surgery, and medial or lateral decompression only. The following clinical parameters were evaluated preoperatively and postoperatively: Hertel exophthalmometry, objective measurement of misalignment using the prism-cover-test, assessment of the field of binocular single vision, and measurement of monocular excursions. In addition, the diameter of the extraocular eye muscles was measured in all preoperative CT scans. RESULTS: We included 327 patients (612 orbits), 126 patients (242 orbits) had no preoperative diplopia. In patients with NOD PP (34%, n = 43/126), enlargement of the medial rectus muscle and restriction of abduction and elevation were significantly more frequent than in patients with no NOD PP. The degree of exophthalmos decrease positively correlated with postoperative squint angle. CONCLUSION: We were able to identify the diameter of the medial rectus muscle, restriction of abduction, and elevation as well as an extensive reduction of exophthalmos as risk factors for NOD PP in patients with no preoperative diplopia.

Graves' Orbitopathy: Current Concepts for Medical Treatment. / Endokrine Orbitopathie: aktueller Stand der medikamentösen Therapie.

BACKGROUND: The therapy of severe manifestations of Graves' orbitopathy (GO) is still a challenge and requires good interdisciplinary cooperation. It is especially important to use stage-adapted anti-inflammatory therapy to avoid irreversible damage. MATERIAL AND METHODS: Discussion of the latest results of multicentre randomised therapy studies on anti-inflammatory treatments for Graves' orbitopathy, as well as new therapeutic concepts. RESULTS: Mild cases of GO can be treated with only selenium supplementation and a watchful waiting strategy. In the moderate-to-severe active form of GO, primary therapy consists of i. v. steroids (cumulative 4 - 5 g) in combination with orbital irradiation in patients with impaired motility. In patients with insufficient therapeutic response after 6 weeks, treatment should be switched to other immunosuppressive agents. In severe sight-threatening disease, bony orbital decompression is usually necessary. As basic research has improved our understanding of the underlying pathophysiology of GO, it has been possible to develop targeted therapies for GO. Teprotumumab, an IGF-1 receptor antibody, was effective in treating GO patients in a phase III trial and should soon be awarded approval for Europe. CONCLUSION: The current therapy concept for Graves' orbitopathy is as follows: first anti-inflammatory therapy then surgical correction of the permanent defects. This may soon be modified, due to the use of targeted therapies.

Modified types of orbital exenteration, survival, and reconstruction.

PURPOSE: This study aims to analyse the various modifications of orbital exenteration. METHODS: Patients undergoing orbital exenteration from March 1978 to October 2019 were included in this retrospective study. The patients were evaluated on the basis of the indication, type of exenteration, reconstruction technique, overall survival (OS), and disease-free survival (DFS). RESULTS: In total, 300 patients were enrolled in this study. As many as 24 patients had lid and conjunctiva sparing anterior exenteration, 16 had lid sparing anterior exenteration, 83 had anterior exenteration, 14 had lid and conjunctiva sparing total exenteration, seven had lid sparing total exenteration, 44 had total exenteration, one had lid and conjunctiva sparing extended exenteration, 23 had lid sparing extended exenteration, and 88 had extended exenteration. As many as 39 patients had a primary wound closure. Six patients underwent reconstruction with a split-thickness skin graft, 177 patients with a local or regional flap, and 40 patients with a microvascular flap. A total of 38 patients did not undergo reconstruction. The mean follow-up was 40 months (range 6-216 months). The OS rate was 82.2% after 1 year, 58.5% after 5 years, and 49% after 10 years for all patients with malignant tumours. The DFS rate was 67.7% after 1 year, 45.6% after 5 years, and 31.7% after 10 years. CONCLUSION: Individual types of orbital exenteration allow patient-adapted therapies. The preservation of uninvolved orbital tissue facilitates orbital reconstruction. The type of exenteration did not have any influence on overall survival.

Visual rehabilitation of patients with corneal diseases.

BACKGROUND: Although most patients with visual impairment due to corneal diseases can be treated successfully with surgery, some require visual rehabilitation to restore reading ability. To evaluate the best LVAs especially in terms of reading speed and characterize this specific patient group we performed a prospective, randomized cross-over trial. METHODS: All 34 patients underwent a detailed examination (slit-lamp, funduscopy, SD-OCT, ETDRS) as screening. Only patients with corneal diseases without other ocular diseases were included. Reading-speed was assessed with International-Reading-Speed-Texts (IReST) consecutively with five different LVAs (low vision aids) during one day in a randomized cross-over design. Corneal haze was quantified with corneal densitometry (Pentacam). RESULTS: Patients were either visually impaired (n = 28), severely impaired (n = 4) or legally blind (n = 2). Patients read significantly faster with LVAs (p < 0.0001). Fastest reading speed could be achieved with video magnifier (CCTV). Optical magnifier and portable-electronic magnifier enabled significantly lower reading speeds (p < 0.01). In a subgroup of patients (VA < 3/60,n = 6) black background enabled patients to read significantly faster compared to white background (p = 0.03). CONCLUSION: Patients with low magnification requirement can be treated successfully with optical LVAs and portable-electronic magnifiers. More severely afflicted patients need a CCTV. Black background enables fastest reading-speeds, probably due to less blinding. Visual impairment can be estimated with corneal densitometry. Our trial confirms the capability of LVAs to successfully restore the reading ability in patients with corneal diseases, which is a crucial part of visual rehabilitation. TRIAL REGISTRATION: This trial was registered at the German Clinical Trials Register as DRKS00010887 at 09.08.2016.

The influence of orbital decompression on objective nasal function in patients with graves' orbitopathy.

PURPOSE: To determine the influence of anatomical changes after orbital decompression to nasal function. METHODS: We examined postoperative nasal function after orbital decompression in patients with GO in a prospective study. 25 patients were enrolled between 2014 and 2016. Sense of smell (Sniffin' Test) and nasal airflow (anterior rhinomanometry) were tested pre- and 6 weeks postoperatively. In addition, postoperative incidence of sinus infections, persistent pressure pain, and infraorbital hypoesthesia were assessed by means of a questionnaire. RESULTS: The olfactory performance showed a significant increase (p < 0.05) after surgery, while the nasal airflow significantly decreased (p < 0.05). Acute sinus infection occurred in three, infraorbital sensibility disorders in eight cases within the first 6 weeks after surgery. No persistent pain was recorded. CONCLUSION: We demonstrate that decompression of the medial orbital wall leads to a decrease in nasal airflow, whereof patients should be informed before the procedure. This is most likely due to a medialization of the medial turbinate and the prolapse of orbital content into the nasal cavity. The increase of the olfactory performance is, in our opinion, more likely due to variation within the standard deviation than to anatomical changes.

Surgical Treatment of Diplopia in Graves Orbitopathy Patients.

PURPOSE: To review the authors' current understanding of motility dysfunction in patients with thyroid eye disease and to summarize appropriate evaluation and available management options. METHODS: Data were retrieved from a systematic search of the literature. RESULTS: Diplopia is one of the most disabling symptoms for Graves orbitopathy patients. It occurs in moderate-to-severe Graves orbitopathy stages and does not respond well to available anti-inflammatory treatment. Inflammation of extraocular muscles induces relatively rapid fibrotic and degenerative changes, which lead to scarring and loss of elasticity with preserved contractility. Inferior and medial rectus muscles are most often involved, which results in horizontal or vertical misalignment or both, and sometimes cyclotorsion. Impaired motility can also be caused by entrapment after orbital decompression. The aim of surgical correction is to restore/enlarge the field of binocular single vision and alleviate abnormal head posture. The basis for successful treatment is dependent on the identification of the involved muscles combined with the correct assessment of motility, misalignment, and binocular single vision. CONCLUSIONS: Due to increased muscle tightness, recessions are the first choice of surgical procedures. Dosing is the most difficult part of the surgery. Several techniques are described: deviation-correction with preoperative determination of the dose, duction-correction either by active or passive intraoperative evaluation of ductions, and the application of adjustable sutures. Achievable success rates are comparable among these techniques but are dependent on the surgeon's experience. Cyclotorsion and misalignment after decompression and combined horizontal and vertical misalignments are more challenging to correct. Those types of deviations need special solutions like surgery on the oblique muscles and the usage of implants. The field of binocular single vision is the main outcome criteria for success, and the quantification may differ for research questions, study designs, and clinical purposes.

[Corrective Surgery of Severe Esotropia after Decompression in Patients with Graves' Orbitopathy - Comparison of Tendon Elongation and Recession of the Medial Rectus Muscle]. / Korrektur horizontaler Schielwinkel nach Dekompressionsoperation bei Patienten mit endokriner Orbitopathie ­ Vergleich von Sehnenverlängerung und einfacher Rücklagerung des M. rectus medialis.

BACKGROUND: Patients with Graves' orbitopathy (GO) often show severe esotropia after decompression surgery, especially in cases with severe enlargement of muscles before decompression. In severely afflicted patients, simple recessions of the medial rectus muscle are not sufficient. In these patients, tendon elongation with bovine pericardium (Tutopatch®) is an alternative for simultaneous resection of the lateral rectus muscle. We retrospectively analysed our clinical data of patients who underwent corrective surgery of the medial rectus following three-wall decompression surgery. METHODS: Patients who underwent classical uni- or bilateral medial recession (MR, BMR; n = 87) or bilateral medial recessions combined with tendon elongation with a graft at one or both muscles (n = 60), were analysed for surgical success (≤ 10 Δ esotropia, central 20° field of binocular single vision), dose effect (° per mm recession/elongation distance) and postoperative ductions. Clinical data directly after surgery and 3 and 12 months later were evaluated in a retrospective manner. RESULTS: All patients showed lower dose effects compared to medial recessions without prior decompression: Unilateral recession 1.2 ± 0.4°/mm, bilateral 1.0 ± 0.3°/mm, unilateral tendon elongation with contralateral simple recession 0.92 ± 0.3°/mm and bilateral tendon elongation 0.87 ± 0.3°/mm. Because of a preoperatively overestimated dose effect, some patients showed undercorrections after surgery. Under consideration of the actual dose effect, surgical success could often be achieved in these severely afflicted GO patients: After simple recessions in 90% and after tendon elongations in 70% of patients. CONCLUSIONS: In patients following three-wall decompression, higher dosages have to be used for medial recessions and recessions with tendon elongation than with patients without prior decompression. Simple recessions are therefore only to be recommended up to 15° esotropia. In more severe cases up to 25°, tendon elongation can be used.

Combination Therapy of Intravenous Steroids and Orbital Irradiation is More Effective Than Intravenous Steroids Alone in Patients with Graves' Orbitopathy.

The aim of this study was to evaluate and compare the efficacy of intravenous (iv) glucocorticoids (GCs) with and without orbital radiotherapy (ORT) in a retrospective analysis of patients with active, moderate-to-severe Graves' orbitopathy (GO). Since diplopia has the strongest impact on quality of life, a careful work up of motility and binocular single vision (BSV) has been performed. The Essen-EUGOGO-Center database (n=3655) was screened for patients with untreated moderate-to-severe, active GO, onset ≤12 months. The inclusion criteria were met by 148 patients (n=76 ivGC, n=72 ivGC + ORT). We analyzed CAS (inactivation: ≤2), NOSPECS, lid-width, proptosis, motility, and field of BSV. To score the overall ophthalmic outcome, a severity-weighted-score (SOS) was compared with an established EUGOGO inflammation-weighted-score (IOS). Cumulative ivGCs dosages and duration of GO did not differ between the groups. Patients with combination therapy had a significantly more severe GO at baseline. Therefore, a subgroup with matched severity was additionally compared. In the IOS, both groups reached similar improvement rates (55.2 vs. 63.9%; p=0.31). However, in the SOS, the rates differed significantly (46.1 vs. 61.1%; p=0.03- unmatched and p=0.03 matched), despite similar rates of inactivation (65.8 vs. 63.8%). Impaired motility improved significantly more often after combination therapy (p=0.01 matched, p=0.004 unmatched). Treatment responders showed only partial improvement (proptosis: 2.5±0.5 mm; motility: 11.3±10.9°). In our retrospective analysis, combination therapy (ivGCs + ORT) was significantly more effective in reduction of severity and should therefore always be considered in moderate-to-severe GO stages, especially in the presence of motility disorders. However, the limited improvement in clinical parameters, despite the promising effect on inactivation of inflammation, has to be outlined to the patients.

Genetic Polymorphisms and the Phenotypic Characterization of Individuals with Early Age-Related Macular Degeneration.

PURPOSE: While the importance of risk polymorphisms for the pathogenesis of age-related macular degeneration (AMD) is well established, their impact on morphological and functional phenotypes is largely unclear. We aimed to characterize individual phenotypes in patients who were either homozygous for a risk allele in the CFH gene, ARMS2 gene, or both as compared to non-carriers. METHODS: Patients with early AMD (n = 85) were assessed during a follow-up examination of a prospective study (MARS) with multimodal diagnostics including SD-OCT and microperimetry. RESULTS: Compared to non-carriers, OCT scans revealed lower retinal thickness in patients homozygous for CFH or ARMS2, which was caused by a significantly reduced photoreceptor layer. The number and ultrastructure of drusen were also significantly different. CONCLUSIONS: These findings indicate that patients with risk alleles demonstrate distinct phenotypic differences of morphology and function as compared to non-carriers. In particular in the CFH group, a loss of photoreceptors occurred concomitantly with reduced retinal sensitivity. Further studies might help to better understand the pathophysiology.

[Graves' orbitopathy as the cause of diplopia in old age-Differences between young and old]. / Endokrine Orbitopathie als Ursache einer Diplopie im Senium ­ Unterschiede zwischen Jung und Alt.

BACKGROUND: Endocrine orbitopathy (EO) is an autoimmune disease mostly associated with a disease of the thyroid gland, which leads to inflammation, adipogenesis and fibrosis. The severity of EO can vary greatly between individuals, which makes it difficult to exactly predict the natural course of the disease; however, this is important to be able to individually adapt the treatment. The aim of this study was to compare the clinical features, course, treatment and prognosis for patients with EO under 50 years old with older patients. The results of the study with a focus on motility are presented in this special issue. PATIENTS AND METHODS: The hospital records of a randomly selected sample of 1000 patients from the EO databank in Essen (GODE), which includes 4260 patients, were analyzed. The patients were divided into two groups: group 1 ≤50 years and group 2 >50 years. Only patients with complete data sets were included in the statistical analyses. RESULTS: Younger patients (n = 484) presented significantly more frequently with milder EO (53% vs. 33%, p < 0.0001), whereas older patients (n = 448) more frequently suffered from moderate or severe forms (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility and clinical activity scores (5.9 vs. 2.3 prism diopters, PD/310° vs. 330°, both p < 0.0001, CAS 2.1 vs. 1.7, p = 0.001). Proptosis and the occurrence of optic nerve compression showed no significant differences between the groups (3% each). Multiple logistic regression showed that the necessity for a second eye muscle surgery was most strongly associated with a previous decompression (OR = 0.12, 95 % CI 0.1-0.2, p < 0.0001), followed by orbital irradiation and age. CONCLUSION: In summary, younger patients with EO presented with milder clinical features, such as a lower rate of restrictive motility disorders and weaker expression of signs of inflammation. Therefore, older patients needed steroids, irradiation, eyelid and eye muscle surgery more frequently; however, the risk of dysthyroid optic neuropathy and the necessity of a second eye surgery were not or only slightly associated with age.

How Age Affects Graves' Orbitopathy-A Tertiary Center Study.

PURPOSE: Graves' orbitopathy (GO) is an autoimmune disorder leading to inflammation, adipogenesis, and fibrosis. The severity of GO can vary widely among individuals, making it challenging to predict the natural course of the disease accurately, which is important for tailoring the treatment approach to the individual patient. The aim of this study was to compare the clinical characteristics, course, treatment, and prognosis of GO patients under 50 years with older patients. METHODS: We reviewed the medical records of a random sample of 1000 patients in our GO database Essen (GODE) comprising 4260 patients at our tertiary referral center. Patients were divided into two groups: Group 1 (≤50 years) and Group 2 (>50 years). Only patients with a complete data set were included in the further statistical analysis. RESULTS: The results showed that younger patients (n = 484) presented significantly more often with mild GO (53% vs. 33%, p < 0.0001), while older patients (n = 448) were more likely to experience moderate-to-severe disease (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility, and clinical activity scores (5.9 vs. 2.3 PD/310° vs. 330° both p < 0.0001, CAS: 2.1 vs. 1.7, p = 0.001). Proptosis and occurrence of dysthyroid optic neuropathy (DON) showed no significant difference between groups (both 3%). Multiple logistic regression revealed that the need for a second step of eye muscle surgery was most strongly associated with prior decompression (OR = 0.12, 95% CI: 0.1-0.2, p < 0.0001) followed by orbital irradiation and age. The model showed good fitness regarding the area under the curve (AUC = 0.83). DISCUSSION: In conclusion, younger GO patients present with milder clinical features such as a lower rate of restrictive motility disorders and less pronounced inflammatory signs. Therefore, older patients tend to need more steroids, irradiation, and lid and eye muscle surgery. Still, the risk of DON and the necessity of secondary eye muscle surgery are not or only slightly associated with age, respectively.

Incidence of A pattern strabismus after inferior rectus recession in patients with Graves' orbitopathy: A retrospective multicentre study.

INTRODUCTION AND PURPOSE: Patients with Graves' orbitopathy (GO) may develop restricted elevation; this can lead to hypotropia, sometimes in combination with an abnormal head posture. Recession of one or both inferior rectus muscles is the first line surgery to restore eye motility in these patients. However, this may result in A pattern strabismus. This study was performed to determine the rate of occurrence of this type of incomitant strabismus and potential predictive factors. METHODS: All patients undergoing surgery on one or two inferior rectus muscles over a 10-year period were screened retrospectively for the A pattern, defined as a ≥5° difference in squint angle between the primary gaze and downgaze. The extraocular muscle thickness in patients with acquired A pattern was determined by computed tomography (CT) and compared with a control group consisting of patients randomly selected from the total cohort. RESULTS: In a total of 590 patients, surgery was performed on the inferior rectus muscle(s) during the study period; the A pattern was identified in 59 patients. Simultaneous surgery was performed on one or both medial rectus muscles in 32% of the patients. This group had significant incyclotorsion (p = 0.000) and less depression (p = 0.000) postoperatively. The mean amount of recession was 4.38 ± 1.53 mm in the A pattern group and 3.91 ± 1.37 mm in the control group (p = 0.032). The amount of depression was 50.2° ± 7.4° in the A pattern group and 57.3° ± 4.4° in the control group (p = 0.045). The inferior rectus muscle was significantly thicker in the A pattern than in the control group (p = 0.027), while there was no significant difference in the thickness of the superior oblique muscle between the two groups (p = 0.870). Of all patients with the A pattern, 47% required further surgery to achieve adequate binocular single vision. CONCLUSION: Increased preoperative inferior rectus muscle thickness and relatively limited depression could be predictors of postoperative A pattern inferior rectus recession in patients with GO. Step-by-step procedures are preferable in this surgically challenging group of patients.