The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy.

BACKGROUND: Optimal doses of i.v. glucocorticoids for Graves' orbitopathy (GO) are undefined. METHODS: We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of i.v. methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit. RESULTS: Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit. CONCLUSIONS: The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.

Graves' orbitopathy in a patient with adrenoleukodystrophy after bone marrow transplantation.

OBJECTIVE: For many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as 'Lorenzo's oil'. Recently, bone marrow transplantation (BMT) has also been used. CASE REPORT: We report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards. EVIDENCE SYNTHESIS: A boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I(131) (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up. CONCLUSIONS: This case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.

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.

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized controlled trial.

OBJECTIVE: Only a small percentage of Graves' ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first-line treatment, thus preventing treatment with steroids. DESIGN AND SUBJECTS: We performed a randomized trial in 15 patients with very active GO and optic neuropathy. Six patients were treated with surgical decompression, and nine with methylprednisolone i.v. pulses for 2 weeks, followed by oral prednisone for 4 months. The primary outcome was determined by changes in visual acuity. If the eye disease deteriorated despite treatment or did not improve sufficiently, patients were switched to the other treatment arm. RESULTS: The severity and activity of GO in both groups were similar at baseline. The Clinical Activity Score (CAS) was 6.3+/- 0.8 in the surgical group vs. 6.0+/- 0.5 in the steroids group and the Total Eye Score was 24+/- 6 vs. 25+/- 6. In the surgery group, 5/6 patients (82%) did not respond because of insufficient improvement in vision (n=3) or persistent chemosis (n=2), and all needed further immunosuppression. In the steroids group, 4/9 patients (45%) did not improve in visual acuity (P=0.132 vs. surgery group), and these needed decompressive surgery. All patients in whom therapy failed were switched to the other treatment arm and visual acuity improved in almost all patients. Visual acuity improved from 0.36 (0.02--0.40) to 0.90 (0.63--1.0) in the surgery group and from 0.50 (0.32--0.63) to 0.75 (0.32--1.0) in the steroids group at 52 weeks. At long-term follow-up in the surgery group 3/6 patients required squint surgery and 5/9 patients in the steroids group. Eyelid surgery was performed in 5/6 patients in the surgery group and in 4/9 patients in the steroids group. CONCLUSION: Immediate surgery does not result in a better outcome and therefore methylprednisolone pulse therapy appears to be the first-choice therapy.

TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves' ophthalmopathy patients.

OBJECTIVE: From in vitro studies using cultures of orbital fibroblasts, it has become clear that cytokines play an important role in the orbital inflammation in Graves' ophthalmopathy (GO). Orbital fibroblasts seem to be the key target cells of the autoimmune attack, and they are able to express the TSH receptor (TSH-R). In vivo data on the presence of cytokines in orbital tissues are sparse, and mostly limited to samples obtained from patients with endstage, inactive GO; the same holds true for the presence of the TSH-R. The aim of the present study was to determine whether the cytokine profile and TSH-R expression differ in the active vs. the inactive stage of GO. DESIGN AND MEASUREMENTS: Orbital fat/connective tissue was obtained from six patients with active, untreated GO undergoing emergency orbital decompression, and from 11 patients with inactive GO subjected to rehabilitative decompressive surgery. The mRNA levels of various cytokines and the TSH-R were assessed by real-time polymerase chain reaction (PCR) using the LightCycler. Data are expressed as ratios (unknown mRNA/beta-actin mRNA). RESULTS: Active GO patients had much higher TSH-R expression than inactive patients: 4/0-24 (median value/range) vs. 0/0-9, P = 0.01. TSH-R expression was related to the Clinical Activity Score (r = 0.595, P = 0.015). Patients with active GO compared to those with inactive GO had higher mRNA levels of the proinflammatory cytokines interleukin-1beta (IL-1beta) (445/153-877 vs. 0/0-455, P = 0.001), IL-6 (1583/968-18825 vs. 559/0-7181, P = 0.01), IL-8 (1422/38-7579 vs. 32/0-1081, P = 0.046) and IL-10 (145/58-318 vs. 27/0-189, P = 0.002). In active GO there also existed a trend towards a predominance of T helper 1 (Th1)-derived cytokines as evident from higher IL-2 (37/0-158 vs. 0/0-68, P = 0.043), interferon-gamma (IFN-gamma) (20/0-79 vs. 0/0-16, P = 0.12) and IL-12 (2.3/0-14.8 vs. 0/0-1.6, P = 0.10) mRNAs. IL-1 receptor agonist (IL-1RA), IL-2 receptor (IL-2R), IL-3, IL-4, IL-5, IL-13, IL-18 and tumour necrosis factor-alpha (TNF-alpha) mRNAs were similar in both groups. CONCLUSIONS: These data show that at the mRNA level, TSH-R expression is largely present only during the active stages of GO. The active phase is characterized by the presence of proinflammatory and Th1-derived cytokines, whereas other cytokines, among them Th2-derived cytokines, do not seem to be linked to a specific stage of GO.

Interpretation and validity of changes in scores on the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments.

OBJECTIVE: The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) is the first instrument available to measure health-related quality of life (HRQL) of patients with Graves' ophthalmopathy. The main objective of this study was to define a minimal clinically important difference (MCID) in score on the GO-QOL that can be considered an important improvement in HRQL by examining changes in GO-QOL scores in patients who subjectively report improvement from their treatment. A secondary objective was to test the longitudinal validity of the GO-QOL, using prespecified hypotheses about expected treatment effects. DESIGN: A prospective cohort study. PATIENTS: We included 164 patients who were scheduled for radiotherapy (23), orbital decompression (10 for sight loss, 38 for exophthalmos), eye muscle surgery (31), eyelid lengthening (43) or blepharoplasty (19). MEASUREMENTS: Patients completed the GO-QOL and three general HRQL questionnaires, before and three or six months after treatment, depending on the performed procedure. Clinical characteristics were collected from the medical records. Mean changes in GO-QOL scores and effect sizes were calculated after different treatments, and in subgroups of responders and nonresponders according to clinical characteristics and according to the patients themselves. RESULTS: A clinical response to treatment was associated with a change in GO-QOL scores of approximately 10--20 points after major treatments (radiotherapy or decompression), and with a change of approximately 3--10 points after minor surgery (eye muscle surgery, eyelid lengthening, blepharoplasty). Changes in GO-QOL scores of about 6--10 points were considered important improvements by the patients themselves. The direction and amount of change in GO-QOL scores after different treatments were in accordance with our prespecified hypotheses about treatment effects. Effect sizes in the GO-QOL subscales were generally higher than effect sizes of the general HRQL subscales, supporting the longitudinal validity of the GO-QOL. CONCLUSIONS: As a general guideline, one could consider a mean change of at least 6 points on one or both subscales an important change in daily functioning for patients. For more invasive therapies, a change of at least 10 points is recommended as a minimal clinically important difference.

[Rehabilitation of anophthalmic patients. Results of a survey]. / Rehabilitation anophthalmischer Patienten. Ergebnisse einer Umfrage.

BACKGROUND: We surveyed ocularists' views on orbital implants, secondary surgical procedures, patient satisfaction, and cooperation between ophthalmologists and ocularists. METHOD: A 14-item questionnaire was sent to all 29 ocularists working in Germany all 4 in the Netherlands. RESULTS: Primary implants are generally recommended, preferably dermofat grafts and ,,baseball" implants. Outcome depends crucially upon surgical procedure and postoperative course. Scepticism is common toward secondary surgical procedures, with the success rate estimated at 70%. Cooperation between ocularists and ophthalmologists is generally regarded as unsatisfactory, also the information provided to the patients by the ophthalmologist after enucleation. CONCLUSIONS: The ocularists demand best possible enucleation techniques including the use of primary implants. However, they are critical toward secondary procedures for correcting postenucleation socket syndrome. Cooperation between ocularists and ophthalmologists need to be improved in providing patient care.

Bony orbital development after early enucleation in humans.

AIM: To analyse the extent of bony orbital volume reduction after enucleation in humans. METHODS: Volumetric studies on bony orbital volumes based on three dimensional reconstructions acquired from high resolution computed tomograph (CT) scans were performed in 29 patients with acquired anophthalmia and four patients before enucleation (controls). Eight patients (follow up 25-52 years) were enucleated in childhood aged between 0.4 and 8 years (group I), 21 in adulthood aged between 15 and 53 years. Fifteen of these patients (group IIa) had long standing anophthalmia (follow up 7-53 years), six patients (group IIb) were enucleated 9 months to 4 years before CT. RESULTS: Bony orbital volumes were reduced in all patients with long standing anophthalmia. The median percentage reduction in enucleated orbits was 7.0% in group I, 3.8% in group IIa, and 1.9% in group IIb. In patients with long standing anophthalmia (I and IIa) the reductions were statistically significantly different (p <0.01) from zero. There was some evidence of a correlation between orbital volume reduction and age at enucleation (rho = 0.36, p = 0.09, Spearman rank correlation coefficient) and a statistically significant correlation between volume reduction and time interval since enucleation (rho = -0.5, p = 0.003). Clinically none of the patients showed significant facial asymmetry. CONCLUSIONS: These data provide strong evidence that enucleation both in children and adults is associated with a reduction of bony orbital volume and that this decrease in volume is associated with increasing time. However, the reduction is smaller than generally assumed and does not cause obvious facial asymmetry. It is more related to the time interval since enucleation than the age at enucleation, which makes a mechanism of volume adaptation more likely than just retardation of growth.

The intranasal ostium after external dacryocystorhinostomy and the internal opening of the lacrimal canaliculi.

The purpose of this paper was to evaluate the appearance and location of the healed intranasal ostium and the internal aperture of the common canaliculus after uncomplicated external dacryocystorhinostomy (DCR). In 21 patients who underwent uncomplicated external DCR, the distances between the lacrimal puncta and the internal aperture of the common canaliculus were measured during surgery. The measurements were taken with a 1 mm diameter Bowman probe graded in millimeters. These measurements were recorded and considered the landmarks for the spatial localization of the internal aperture of the canaliculus. After surgery, under endoscopic control, the same method was used to measure the distance between the lacrimal puncta and the internal ostium, which was defined as the aperture through which it was possible to visualize the very first protrusion of the probe into the nose. The intra- and post-operative measurements were compared. Endoscopic photos of the healed endonasal ostium were also taken. The photos showed that when DCR procedures were not complicated by scarring or mucosal adhesions, the lacrimal sac became a depression perfectly integrated within the nasal mucosa. The scar at the site of junction between the nasal and the lacrimal sac mucosa appeared as a large-diameter pearl-like colored frame that surrounded the depression. In the context of the depression a small aperture, which presented a diameter of around 2 mm, could be easily visualized. The spatial location of this aperture corresponded to the internal aperture of the common canaliculus (p < 0.05).

[Long-term results of secondary orbital implants]. / Langzeitergebnisse sekundärer Orbitaimplantate.

BACKGROUND: Secondary orbital implants are used for the correction of the post-enucleation socket syndrome (PESS). This study evaluates retrospectively the post-operative course, complications, additional surgery, long-term cosmetic and functional results, and patient's satisfaction after secondary orbital implants. PATIENTS: Nineteen out of 24 patients who underwent secondary baseball implant insertion between 1986 and 1989 for the correction of PESS were re-examined. RESULTS: Five patients had complications, 11 patients (58%) further surgery. After a mean follow-up of 8.6 years, 17 patients (89%) showed findings better than preoperatively. Two patients were unchanged. The static overall impression, assessing particularly volume deficit and symmetry, using a scale of 1 to 5, was improved from 4.5 preoperatively to 2.5. CONCLUSIONS: Secondary orbital implants improve symptoms of PESS and patient's satisfaction in a high proportion of cases also in the long term. Complications are not rare, and frequently more than one operation is necessary. There is no significant risk of long-term side effects and no reduction of the positive effect with time.

A comparison of skin storage methods for oculoplastic surgery.

PURPOSE: To assess the level of contamination of full-thickness skin grafts stored with or without an antibiotic cover. METHODS: Full-thickness skin grafts were harvested from 40 bilateral upper lid blepharoplasties. Before surgery the face was sterilised, the head of the patient was packed with sterile, single-use surgical drapes and the whole face was left exposed. The harvested full-thickness skin grafts were conserved in sterile containers at 4 degrees C for 6 days, rolled in gauze moistened with either 4 ml of sterile saline solution (group I) or with 4 ml of gentamicin solution (2 mg/ml) (group II). The degree of contamination, expressed in colony forming units (CFU), was evaluated on days 2, 3, 4, 5 and 6. Identification of the microorganisms was done to species level following standard procedures and commercial methods. RESULTS: In group I 2 grafts (5%) were negative during the whole observation period while the other 38 grafts (95%) presented a degree of contamination ranging from 10(2) to 10(4) CFU. Microorganisms isolated were: Staphylococcus epidermidis (24 cases), Staphylococcus aureus (5 cases), Staphylococcus saprophyticus (2 cases), Pseudomonas aeruginosa (4 cases), Serratia liquefaciens (1 case) and Klebsiella oxytoca (2 cases). In group II, 26 grafts (65%) were negative during the whole observation time while in 14 cases (35%) a few colonies (3 to 6) of Candida albicans were isolated on day 2 and remained constant in number for the whole observation time. CONCLUSIONS: The storage of full-thickness skin graft with an antibiotic cover is more reliable than the storage of full-thickness skin graft without an antibiotic cover.

Sensitivity and specificity of ultrasonography, fluorescein videoangiography, indocyanine green videoangiography, magnetic resonance and radioimmunoscintigraphy in the diagnosis of primary choroidal malignant melanoma.

The prognosis of primary choroidal malignant melanoma (PCMM) is fatal if no early reliable diagnosis is performed. Any incisional biopsy is impossible, and diagnosis is only based on instrumental examinations. The purpose of this study is to evaluate the reliability of ultrasonography, fluorescein videoangiography (FV), indocyanine green videoangiography (ICGV), magnetic resonance (MR) and radioimmunoscintigraphy (RIS) in the diagnosis of PCMM in a series of 12 eyes in which the tumor was suspected. A presumed diagnosis of PCMM was made when a positive result was obtained with 3 or more methods. The presumed diagnosis was then compared with histological findings (true value) in 4 enucleated eyes. The sensitivity and specificity of every single method were evaluated comparing its results with the final presumed diagnosis and with the histological findings. Sensitivity and specificity of every single method have been expressed as percentage of correspondence with the presumed diagnosis. Sensitivity was 100% for ultrasonography, MR, FV, ICGV and 67% for RIS. Specificity was 92% for ultrasonography, 87% for RIS, 83% for MR and 82% for FV and ICGV. This study indicates that the ophthalmologist can obtain a good diagnostic reliability in the case of PCMM using only ultrasonography, FV and ICGV. Besides MR and RIS are important adjunctive methods to ophthalmological investigations for the diagnosis of PCMM.

Ultrasonographic and angiographic follow-up of primary choroidal malignant melanoma after proton beam irradiation therapy.

The aim of this study is to evaluate the reliability of the ultrasonographic and angiographic follow-up of primary choroidal malignant melanoma (PCMM) after proton beam irradiation therapy in a series of 14 patients. All patients underwent standardized A and B scan ultrasonography, fluorescein and indocyanine green videoangiography (FV, ICGV) before and after treatment with proton beam irradiation. The follow-up was carried out at 1, 3, 5, 8 months and then every 6 months. The mean follow-up was 26 months (range 6-46 months). The thickness of the tumors was demonstrated to be decreased and the internal reflectivity to be enhanced in 12 out of 14 cases from 8 months after treatment till the end of the follow-up period. In 2 eyes which were enucleated 5 months after treatment, histopathology confirmed that medium-low internal reflectivity corresponded to several areas of high cellularity and cellular mitosis. FV and ICGV were impossible because of opacities of dioptric media in 2 cases. From 8 months after treatment till the end of the follow-up period, in all the examined patients, FV demonstrated large hypofluorescent zones of the lesions which represented the destruction of the vascular tree of the tumor. From 8 months after treatment till the end of the follow-up period, ICGV demonstrated hypofluorescence of the lesions in 8 cases; mild hyperfluorescence and zones of colorant staining were present in late angiograms in 2 cases. The results of our study seem to confirm the reliability of standardized A and B scan ultrasonography in the follow-up of PCMM treated with proton beam irradiation; if ultrasonography is used together with FV and ICGV, the reliability of this combination is surely higher.

Ultrasonographic follow-up of primary choroidal malignant melanoma after proton beam irradiation therapy.

The aim of this study is to evaluate the ultrasonographic aspects of primary choroidal malignant melanoma (PCMM) after proton beam irradiation therapy and the reliability of its ultrasonographic follow-up in a series of 10 patients. All patients were examined with standardized A and B scan ultrasonography before and after treatment with proton beam irradiation therapy. The follow-up was carried out at 1, 3, 5, 8 months and then every 6 months. The mean follow-up was 20 months (range 6-34 months). The thickness of the tumors was demonstrated to be decreased and the internal reflectivity to be enhanced in 9 out of 10 cases from 8 months after treatment till the end of the follow-up period. Histopathology confirmed in 1 eye enucleated 5 months after treatment that medium-low internal reflectivity coresponded with several areas of high cellularity and cellular mitosis. The results of our study indicate the reliability of standardized A and B scan echography in the follow-up of PCMM treated with proton beam irradiation therapy.