Kostas G. Boboridis

Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO

Summary of consensus a. All patients with GO should (Fig. 1):Be referred to specialist centers;Be encouraged to quit smoking;Receive prompt treatment in order to restore andmaintain euthyroidism.b. Patients with sight-threatening GO should be treatedwith i.v. GCs as the first-line treatment; if the responseis poor after 1–2 weeks, they should be submitted tourgent surgical decompression.c. The treatment of choice for moderate-to-severe GO isi.v. GCs (with or without OR) if the orbitopathy isactive;surgery(orbitaldecompression,squintsurgery,and/or eyelid surgery in this order) should beconsidered if the orbitopathy is inactive.d. In patients with mild GO, local measures and anexpectant strategy are sufficient in most cases, buttreatment may be justified if QoL is affectedsignificantly. In memoriam This document is dedicated to the memory of MarkPrummel (1956–2005), one of the founders ofEUGOGO, who greatly contributed to expanding ourunderstanding of clinical and therapeutic aspects of GO.

Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy.

Luigi Bartalena, Lelio Baldeschi, Alison J. Dickinson, Anja Eckstein, Pat Kendall-Taylor, Claudio Marcocci, Maarten P. Mourits, Petros Perros, Kostas Boboridis, Antonella Boschi, Nicola Curro, Chantal Daumerie, George J. Kahaly, Gerasimos Krassas, Carol M. Lane, John H. Lazarus, Michele Marino, Marco Nardi, Christopher Neoh, Jacques Orgiazzi, Simon Pearce, Aldo Pinchera, Susanne Pitz, Mario Salvi, Paolo Sivelli, Matthias Stahl, Georg von Arx, and Wilmar M. Wiersinga

Role of Hyperosmolarity in the Pathogenesis and Management of Dry Eye Disease: Proceedings of the OCEAN Group Meeting

Dry eye disease (DED), a multifactorial disease of the tears and ocular surface, is common and has a significant impact on quality of life. Reduced aqueous tear flow and/or increased evaporation of the aqueous tear phase leads to tear hyperosmolarity, a key step in the vicious circle of DED pathology. Tear hyperosmolarity gives rise to morphological changes such as apoptosis of cells of the conjunctiva and cornea, and triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. This exacerbates tear film instability and drives the cycle of events that perpetuate the condition. Traditional approaches to counteracting tear hyperosmolarity in DED include use of hypotonic tear substitutes, which have relatively short persistence in the eye. More recent attempts to counteract tear hyperosmolarity in DED have included osmoprotectants, small organic molecules that are used in many cell types throughout the natural world to restore cell volume and stabilize protein function, allowing adaptation to hyperosmolarity. There is now an expanding pool of clinical data on the efficacy of DED therapies that include osmoprotectants such as erythritol, taurine, trehalose and L-carnitine. Osmoprotectants in DED may directly protect cells against hyperosmolarity and thereby promote exit from the vicious circle of DED physiopathology.

Clinical Features of Dysthyroid Optic Neuropathy: A European Group on Graves Orbitopathy (EUGOGO) Survey

Background: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. Methods: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. Results: Graves’ hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. Conclusion: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.

Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures

Aim: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves’ orbitopathy (GO) receiving surgery for disfiguring proptosis. Method: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. Results: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. Conclusions: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction

Meibomian gland dysfunction (MGD) is the most frequent cause of dry eye disease (DED). Eyelid inflammation, microbial growth, associated skin disorders as well as potentially severe corneal complications culminate to make MGD a complex multifactorial disorder. It is probable that MGD is a heterogeneous condition arising from any combination of the following five separate pathophysiological mechanisms: eyelid inflammation, conjunctival inflammation, corneal damage, microbiological changes and DED resulting from tear film instability. The pathogenesis of both MGD and DED can be described in terms of a ‘vicious circle’: the underlying pathophysiological mechanisms of DED and MGD interact, resulting in a double vicious circle. The MGD vicious circle is self-stimulated by microbiological changes, which results in increased melting temperature of meibum and subsequent meibomian gland blockage, reinforcing the vicious circle of MGD. Meibomian gland blockage, dropout and inflammation directly link the two vicious circles. MGD-associated tear film instability provides an entry point into the vicious circle of DED and leads to hyperosmolarity and inflammation, which are both a cause and consequence of DED. Here we propose a new pathophysiological scheme for MGD in order to better identify the pathological mechanisms involved and to allow more efficient targeting of therapeutics. Through better understanding of this scheme, MGD may gain true disease status rather than being viewed as a mere dysfunction.

Failure of rituximab treatment in a case of severe thyroid ophthalmopathy unresponsive to steroids

metric fluorescent assay with a functional sensitivity of 0Æ1 ng/ml. Algeciras-Schimnich et al. recently reported in a cohort of 197 healthy subjects (98 males and 99 females) a reference upper limit for CT of 16Æ0 ng/ml for males and 8Æ0 ng/ml for females and for proCT of 0Æ15 ng/ml. The v was employed to compare the positive rate of each marker and a P-value < 0Æ05 was considered to be statistically significant. Elevations in CT and ProCT were observed in five (2Æ9%) and one (0Æ5%) of 168 patients, respectively (P < 0Æ01). None of the patients with DTC and healthy controls had a false-positive CT or proCT result. Four of five patients with increased CT (included the only one with positive proCT) had nodular lymphocytic thyroiditis (Table 1). In our series, a falsepositive serum CT was found in four patients with nodular lymphocytic thyroiditis and one with hyperplastic goitre whereas none of the patients with DTC had an increased serum CT (overall false positive rate: 2Æ9%). Reactive C-cell hyperplasia (CCH) in neonates, elderly age, hyperparathyroidism, Hashimoto’s thyroiditis and follicular thyroid adenomas have been reported to increase serum CT concentrations. Accordingly, three and one of our five CT-positive patients, all with lymphocytic thyroiditis, displayed reactive CCH and borderline increased C-cell counts, respectively. Inflammatory mediators and cytokines secreted by infiltrating lymphocytes in the thyroid parenchyma may be involved in reactive CCH with CT secretion in these patients. Interestingly, only one patient had a slight increase in serum proCT in our series (0Æ5% false-positive rate). Particularly, a negative proCT measurement could have been excluded 80% of CT-positive patients from stimulation tests and/or invasive diagnostic procedures in our series. In conclusion our data suggest that proCT is more specific than CT in patients presenting with nonmedullary thyroid nodules.

Management of canalicular obstructions.

Purpose of review The successful treatment of canalicular obstructions continues to represent a therapeutic challenge. Conjuctivodacryocystorhinostomy with a Lester Jones bypass tube is the standard treatment in these situations. Although a high rate of anatomic success can be achieved with this procedure, a relatively high rate of complications and poor patient satisfaction have been reported. Because of this, alternative techniques have emerged. Herein, we review all these techniques described in the literature. Recent findings Increasing interest in minimally invasive surgery and developments in fiberoptic technology have fueled advances in endocanalicular surgery. Canalicular trephination for obstructions at any level of the canalicular system and laser and balloon canaliculoplasty for focal canalicular and common canalicular stenoses may offer a well tolerated, fast and easy alternative, with potentially better patient satisfaction when compared with conjuctivodacryocystorhinostomy. Summary The alternative techniques to conjuctivodacryocystorhinostomy are less invasive, and respect and utilize any healthy and functional part of the canalicular system. The correct choice of the technique for a given canalicular obstruction, and therefore the long-term success, depends on the site and degree of the obstruction.

Cryopreserved amniotic membrane transplantation for the management of symptomatic bullous keratopathy.

Background:  To report the results of cryopreserved human amniotic membrane transplantation for the management of symptomatic bullous keratopathy.

Endoscopic Placement of Jones Lacrimal Tubes with the Assistance of Holmium YAG Laser

Introduction: The aim of this paper is to highlight the use of the Holmium YAG laser in the endoscopic placement of Lester Jones tubes in patients with a blocked canaliculus or failed lacrimal pump function. Materials and methods: Sixteen cases with a non-functional canaliculus were included over a one-year period. Following caruncle excision, a 19G needle is inserted through the medial canthal tissues into the nasal space. Nasal endoscopy confirms the accurate positioning in relation to the nasal anatomy. With the Holmium YAG laser, a tissue channel is fashioned around the guide needle through the structures of the lateral nasal wall to facilitate an accurate and secure placement of the Jones tube. Results: The endoscopic, laser-assisted placement reduces the operating time to less than 20 minutes, minimizes tissue trauma and does not require the initial surgical steps of an open DCR procedure. There were 14 cases (87.5%) with securely retained tubes and two cases (12.5%) that required tube replacement. The advantage of the procedure is especially great in revision surgery where the ostium is opened through scar tissue. Conclusions: Nasal endoscopy with the assistance of the Holmium YAG laser offers simplicity and precision in the placement of Jones tubes. It minimizes tissue trauma and increases the surgical success rate.