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.

The use of lyophilized bovine pericardium (Tutopatch®) in the management of third nerve palsy following prior conventional strabismus surgery - a case series.

To study the secondary management of strabismus due to third nerve palsy using bovine pericardium (Tutopatch®) when previous conventional surgical therapy had failed. Review of our clinic records of selected patients with third nerve palsy, in whom residual deviation had been managed using Tutopatch® after previous surgical correction. The squint angle was measured preoperatively, and at 1 day, 3 months, and if possible 6 months postoperatively. Nine patients were enrolled in this study. One patient had mainly residual vertical deviation and was corrected with tendon elongation of the contralateral superior rectus. Three patients were operated on with tendon elongation of the lateral rectus muscle with or without medial rectus muscle resection and/or advancement (Group 1). Lateral rectus splitting after tendon elongation in addition to the resection and/or advancement of the medial rectus was performed in five patients with complete third nerve palsy (Group 2). In Group 1, the preoperative median squint angle was -20° (range -17° to -25°), which improved postoperatively to -4.5° (range -12° to +3°). In Group 2, the preoperative horizontal and vertical median squint angles were -27° (range -20° to -40°) and 0.5° (range 0° and 20°), respectively. Postoperatively, they had improved to -12.5° (range-2° to -25°), and 1.5° (range 0° to 7°), respectively. Two patients of Group 2 were re-operated due to residual exotropia. No postoperative complications were observed in any patient. In this small series several complex re-do situations of patients with third nerve palsy were evaluated in which Tutopatch® markedly improved outcomes after an initially ineffective surgical management. For better evaluation of its usefulness a study with more patients is recommended.

The Nasolacrimal Drainage System in 143 Children with the Microphthalmos-Anophthalmos Complex. / Tränenwegsbefunde von 143 Kindern mit Mikrophthalmus-Anophthalmus-Komplex.

BACKGROUND: Report of clinical findings relating to the lacrimal system in congenital clinical anophthalmos and severe blind microphthalmos (MAC-complex patients). METHODS: A retrospective study of the notes of 207 consecutive patients treated surgically at least once with highly hydrophilic self-inflating expanders for MAC between 1998 and 2021. The lacrimal drainage system was always probed and irrigated under general anaesthesia before any other procedure was started. RESULTS: 64 patients were excluded due to possible misdiagnosis because of previous lid or orbit surgery elsewhere or due to missing data. The analysis therefore included 67 girls and 76 boys aged between 1 and 126 months (median age: 5 months). 72 patients presented with unilateral and 42 with bilateral anophthalmos, and 24 had unilateral and 5 bilateral microphthalmos; consequently, 286 orbits (of which, 190 with probable pathology) were available for assessment. In unilateral cases the lacrimal system on the normal side was never affected. On the anophthalmic or microphthalmic side the lacrimal system was normal in 68 orbits only (35.8%). The most frequent finding was canalicular stenosis (91 orbits; 48%). Common canaliculus stenosis was observed in 12 orbits (6.3%) and nasolacrimal duct obstruction in 9 orbits (4.7%). There were four cases of punctal aplasia, but no other anomalies. In unilateral MAC pathologic findings during lacrimal probing were found to be associated with anatomical malformation of the contralateral fellow eye. Only in unilateral anophthalmos there was a significant association with cleft lip and palate, which was not found in the three other groups. CONCLUSIONS: In congenital clinical anophthalmos the lacrimal system is affected in up to 66.5% of cases, mostly due to canalicular stenosis. Even if there is no clear evidence of an embryological connection, this association is certainly not a random finding.

Postoperative Behaviour after Primary Strabismus Surgery in Children: Is There an Influence of Intraoperative Topical Anaesthesia? / Aufwachverhalten nach primärer Augenmuskeloperation im Kindesalter: Gibt es einen Einfluss einer intraoperativen Oberflächenanästhesie?

INTRODUCTION: The course of the recovery phase after general anaesthesia, during which consciousness and pain gradually return, is essentially determined by the choice of anaesthetic drug, and its total dose or duration of application. This phase is often complicated by more or less severe agitation, especially in children. In the present study we investigated whether the application of a topical anaesthetic to the conjunctiva at the end of a strabismus operation had a positive effect on the recovery behaviour of the child. PATIENTS/METHODS: This prospective, randomised, blinded study was conducted with 50 healthy, ASA class I or II children, aged 3 to 8 years undergoing their first strabismus operation. Following the surgeon's randomisation two drops of a 0,5% tetracaine-HCl ophthalmic solution were applied to the operated conjunctiva three times at 30-s intervals immediately following wound closure. The postoperative evaluation encompassed heart rate, as well as COMFORT and CHEOPS scores. The first assessment was directly postoperatively with repetitions at 15, 30, 45, 60, 75, 90 and 120 min, as well as on the day after surgery. RESULTS: The CHEOPS scores did not differ significantly between children with or without topical anaesthesia at any time during the observation period. The COMFORT scores revealed a slight, but non-significant analgesic effect at 15 and 30 min. The 60 min score showed the opposite effect, possibly indicating a slight disadvantage of the topical anaesthesia. There were no significant differences with regard to time to first request for additional systemic analgesia, to the total dose of systemic pain medication, or to when the patient was eligible for discharge to the ward. CONCLUSION: The application of topical tetracaine-HCl immediately after wound closure had no positive effects on the course of the postoperative recovery period after strabismus surgery in children. There was no evidence of an effect on pain or emergence agitation.

[Efficacy and Side Effects of Lateral Orbital Wall Decompression Including the Orbital Rim in Patients with Graves' Orbitopathy]. / Effektivität und Risiken der tiefen lateralen knöchernen Orbitadekompression mit Entfernung der Orbitakante bei endokriner Orbitopathie.

BACKGROUND: Graves' orbitopathy is the most common extrathyroidal manifestation of Graves' disease. In the burnt out fibrotic phase exophthalmos, diplopia and lid retraction may remain, which can require multiple rehabilitative surgical interventions. Orbital decompression is an established surgical procedure for the treatment of exophthalmos in Graves' orbitopathy. The aim of the study was to evaluate the efficacy and side effects of the deep lateral orbital wall decompression including the orbital rim. METHODS: In this retrospective, non-comparative case series, all patients with Graves' orbitopathy, who underwent lateral orbital wall decompression at the Eye Clinic of the University of Göttingen between 2008 and 2015, were analysed in terms of exophthalmos reduction, diplopia (Gorman score) and complications. The surgical technique involved the removal of the lateral orbital wall including the orbital rim combined with additional orbital fat resection via swinging eyelid approach. RESULTS: 127 patients who underwent 195 orbital decompressions were included. Mean exophthalmos reduction was 4.0 ± 1.2 mm (range 1.5 - 7.5 mm). Preoperatively, 47 patients/77 orbits (37.0/39.5%) presented without diplopia. Postoperatively, 3 patients/3 orbits (6.4/3.9%) showed new-onset diplopia (2.4% of all patients, 1.5% of all orbits). Diplopia in primary gaze was noted in one of the 3 patients (0.8% of all patients, 2.1% of patients without preoperative diplopia), and inconstant diplopia was seen in the other 2 patients. Postoperative improvement of diplopia was noted in 19 patients/19 orbits (15.0% of all patients, 23.8% of patients with preoperative diplopia/9.7% of all 195 interventions), and 16.1% of cases with preexisting diplopia. No severe complications were seen, except for one case of postoperative bleeding, which was successfully managed surgically without any functional deficits. A visible scar formation was noted in 6 cases (3.1%), temporal hollowing in 3 cases (1.5%), oscillopsia when chewing in 3 cases (1.5%) and a de-insertion of the lateral canthal region in 2 cases (1%). CONCLUSIONS: Deep lateral orbital wall decompression, including the orbital rim, is an effective surgical technique to reduce exophthalmos in patients with Graves' orbitopathy with a low risk of functional and aesthetic complications.

Processed amniotic membrane for conjunctival reconstruction in complex strabismus surgery.

INTRODUCTION: In ophthalmology amniotic membrane is usually used for the treatment of corneal ulcerations and chemical burns of the ocular surface. Also, it is useful in the treatment of conjunctival defects. There are few publications on the long-term outcomes with the use of amniotic membrane to replace the conjunctiva. In our cases, we used it in patients with restrictive strabismus or conjunctival problems during or following complex eye muscle surgery. MATERIALS AND METHODS: In this retrospective case study, we reviewed the charts of the patients who had been treated with Ambio5® (IOP Inc. USA) for the replacement of conjunctiva in the treatment of conjunctival problems during or following complex eye muscle surgeries in our ophthalmology department between 2009 and 2015. Ambio5® is a processed dry, multi-layered amniotic membrane of 110-micron thickness. Inclusion criteria were the use of it in the treatment of conjunctival problems during or following complex eye muscle surgery. RESULTS: Thirty-two patients were identified. Among the 32 identified patients, 7 patients (6 female, 1 male) had restrictive conjunctiva following complex strabismus surgery with functional problems or aesthetic conjunctival scarring requiring transplantation. The mean age of these patients was 47 years (range: 22-60 years). Mean follow-up time was 32 months (range 18-55 months). Only one of these seven patients suffered a discomfort related to conjunctival scarring. The other six patients had restrictive strabismus, four of them suffered from Graves' ophthalmopathy. All patients improved although three patients developed symblepharon. One of these patients needed revision because of a symblepharon. DISCUSSION: The result of our study indicates that commercially prepared amniotic membrane is a good alternative graft to replace conjunctiva. It helps to prevent or cure restrictive strabismus, scarring of the conjunctiva with discomfort, and lack of conjunctiva. It is possible that commercially storable products may increase the risk of symblepharon, the reason is unknown.

The Antiproliferative Effect of Bevacizumab on Human Tenon Fibroblasts Is Not Mediated by Vascular Endothelial Growth Factor Inhibition.

PURPOSE: Vascular endothelial growth factor-signaling in human tenon fibroblasts (hTFs) has recently become a target for antifibrotic treatment in glaucoma filtration surgery. The anti-VEGF antibody bevacizumab (BVC) has been shown to increase filtration bleb size. Given the relatively high concentration of BVC needed to obtain an effect, we investigated whether BVC acts through VEGF inhibition or via non-antigen-dependent ways. METHODS: Human tenon fibroblast primary cultures were obtained from strabismus surgery subjects. Under low (0.2%) and high (10%) serum conditions, cells were incubated with BVC, ranibizumab (RNB), aflibercept (AFB), or rituximab (RTX) at different concentrations. Total number of cells and number of dead or proliferating (5-bromo-2-deoxy-uridine-positive) cells were assessed after 24 hours. Concentrations of VEGF-A in cell culture media was measured with ELISA. Intracellular IgG was detected with immunostaining and Western blot analysis. RESULTS: In quiescent hTF culture (0.2% serum) the addition of 5 mg/mL BVC induced widespread cell death. Under proliferative conditions (10% serum), BVC reduced the number of proliferating cells. No such effect was observed with 2.5 mg/mL BVC or with 10 mg/mL AFB or 2.5 mg/mL RNB, although they were equally effective in binding free VEGF-A in the culture media. Instead, the CD20 antibody RTX, which did not bind VEGF, induced hTF death and inhibited proliferation in a BVC-comparable fashion. Bevacizumab, AFB, and RTX were detected intracellularly in a concentration-dependent manner. CONCLUSIONS: The cell death-inducing and antiproliferative effect of 5 mg/mL BVC appeared not to depend on VEGF inhibition. Our data question a direct role of VEGF for hTF survival and proliferation.