Gut Microbiome Associated With Graves Disease and Graves Orbitopathy: The INDIGO Multicenter European Study.

CONTEXT: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO). OBJECTIVE: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs). METHODS: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components. RESULTS: At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment. CONCLUSION: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.

Impact of Upper Eyelid Surgery on Symptom Severity and Frequency in Benign Essential Blepharospasm.

OBJECTIVE: To assess the impact of periocular surgery, other than orbicularis stripping, on the severity and frequency of blepharospasm symptoms. METHODS: Consecutive patients with benign essential blepharospasm (BEB) who underwent eyelid/eyebrow surgery with the aim of improving symptoms were retrospectively reviewed over a 5-year period. Patients who had completed the Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BDI) pre- and at least 3 months postoperatively were included. RESULTS: Twenty-four patients were included. JRS scores significantly improved from 7.0 preoperatively to 4.1 postoperatively (p < 0.001), and BDI scores significantly improved from 18.4 preoperatively to 12.7 postoperatively (p < 0.001); the mean percentage improvements were 41% and 30%, respectively. Patients were followed for a median of 24 months postoperatively. CONCLUSION: Periocular surgery significantly reduced BEB symptoms in the majority (83%) of patients by an average of 33% and may therefore be offered for suitable patients. An important minority (17%) of patients experienced symptom worsening.

Stroke-induced resolution of primary blepharospasm: evidence for the lenticular nucleus as a control candidate.

Primary blepharospasm is an adult-onset focal dystonia characterised by involuntary contractions of the orbicularis oculi, leading to bilateral spasmodic closure of the eyelids. While spasms of this muscle constitute the hallmark of disease, other motor manifestations include increased spontaneous blinking and apraxia of eyelid opening. Originally misdiagnosed as a psychiatric condition, blepharospasm is now well established as being of neurological origin although questions remain as to its pathophysiological mechanisms.We report a 66-year-old woman who had a 14-year history of primary blepharospasm which completely resolved following a left medial cerebral artery thromboembolic infarct of the lenticular nucleus. This report provides supporting evidence of the lenticular nucleus as a key structure mediating the disease which can lead to functional blindness.

Microstructure and mechanical properties of synthetic brow-suspension materials.

Levator palpebrae superioris (LPS) is a muscle responsible for lifting the upper eyelid and its malfunction leads to a condition called "ptosis", resulting in disfigurement and visual impairment. Severe ptosis is generally treated with "brow-suspension" surgery, whereby the eyelid is cross-connected to the mobile tissues above the eyebrow using a cord-like material, either natural (e.g. fascia lata harvested from the patient) or a synthetic cord. Synthetic brow-suspension materials are widely used, due to not requiring the harvesting of fascia lata that can be associated with pain and donor-site complications. The mechanical properties of some commonly-used synthetic brow-suspension materials were investigated--namely, monofilament polypropylene (Prolene®), sheathed braided polyamide (Supramid Extra® II), silicone frontalis suspension rod (Visitec® Seiff frontalis suspension set), woven polyester (Mersilene® mesh), and expanded polytetrafluoroethylene (Ptose-Up). Each material underwent a single tensile loading to the failure of the material, at three different displacement rates (1, 750 and 1500 mm/min). All the materials exhibited elastic-plastic tensile stress-strain behaviour with considerable differences in elastic modulus, ultimate tensile strength, elastic limit and work of fracture. The results suggest that, as compared to other materials, the silicone brow-suspension rod (Visitec® SFSS) might be the most suitable, providing relatively long-lasting stability and desirable performance. These findings, together with other factors such as commercial availability, cost and clinical outcomes, will provide clinicians with a more rational basis for selection of brow-suspension materials.

Systematic internet-based review of complementary and alternative medicine for glaucoma.

OBJECTIVE: To identify the most popular forms of complementary and alternative medicine (CAM) for glaucoma on the Internet and to assess the quality of the most popular Web sites addressing CAM for glaucoma. DESIGN: Systematic Internet-based search. METHODS: Using a predefined search algorithm, Web sites most likely to receive hits from people searching the Internet for information on CAM therapies for glaucoma were identified. MAIN OUTCOME MEASURES: Web sites were evaluated for quality based on the Sandvik score. Each Web site was also assessed for external validation based on listing on the Health on the Net (HON) Foundation Web site in accordance with their code of approval. Finally, the risk each Web site potentially posed to patients was assessed using a previously described scoring method. RESULTS: Twenty-one Web sites were included in our study. Forty-four different CAM therapies were encountered; vitamin C supplements, forskolin, and diet and lifestyle modulation were the most common CAMs discussed. The mean Sandvik score for all Web sites was 9.4 (standard deviation, 2.6). Only one Web site was listed in the HON Foundation code of approval. Two of the 21 Web sites received the highest risk scores of 3 of a potential 4 points. None of the Web sites discouraged adhering to a clinician's advice. Fourteen of the 21 Web sites assessed provided commercial details promoting CAM, with the possibility of purchasing remedies or arranging consultations. Thirteen Web sites provided opinions and experiences without factual details. CONCLUSIONS: Medical information conveyed over the Internet is of variable quality and is not subject to regulation. Many sources of information contain advice on therapies that have no evidence base and may put patients at risk. It is important that researchers and health care providers be aware of the content and quality of this information so as to offer advice to patients about the evidence and potential risks of CAM therapies. This can only be achieved by increasing awareness among ophthalmologists of the range of products and quality of information available for CAM therapies for glaucoma.