Clinical characteristics and the treatment modalities of Graves' orbitopathy in a tertiary referral center in Turkey: changes over two decades.

PURPOSE: To evaluate the changes in demographics, clinical findings, and treatment modalities in Graves' orbitopathy (GO) patients at a tertiary referral center in Turkey over the last two decades. METHODS: The clinical data of 752 GO patients were evaluated retrospectively. Patients were divided into 2 groups according to the first ophthalmic examination date; Group 1(n:344) between January 1998 and December 2007 and Group 2(n:408) between January 2008 and December 2017. RESULTS: The number of nonsmokers was significantly higher in Group 2 (44.0 vs. 26.5%, p < 0.001). The time from the diagnosis of thyroid dysfunction and referral to our center was 32.4 months in Group 1 and 34.8 months in Group 2, (p = 0.166). The most common treatment of hyperthyroidism was antithyroid medications. Radioiodine ablation treatment rate was significantly lower in Group 2 (14.8 vs. 9.1%, p < 0.001). The time between the diagnosis of thyroid disease and orbital involvement was 22.0 vs. 26.6 months in Groups 1 and 2, respectively (p = 0.009). The time elapsed between the diagnosis of orbital disease and referral to our clinic was 21.0 months vs. 22.4 months in Group 1 and 2, respectively (p = 0.068). Orbital disease was most commonly mild, and inactive. Mild and moderate to severe GO and the mean Clinical Activity Score significantly increased, and the rate of sight-threatening disease and orbital decompression surgery significantly decreased in Group 2 (p = 0.042; p < 0.001, respectively). CONCLUSIONS: Mild and inactive orbital disease was the most common form of GO. The severity of GO is declining over the last two decades in Turkey.

Mechanical transnasal endoscopic dacryocystorhinostomy versus transcanalicular multidiode laser dacryocystorhinostomy: long-term results of a prospective study.

The purpose of this study is to compare two dacryocystorhinostomy (DCR) techniques in epiphora treatment. This study is a prospective randomized trial. Twenty-nine patients presenting persistent epiphora due to primary acquired nasolacrimal duct obstruction (PANDO) were included in the study. Two groups each consisting of 15 eyes were formed. Mechanical transnasal endoscopic DCR (MTE-DCR) was applied to the first group, while transcanalicular dacryocystorhinostomy with multidiode laser (TCML-DCR) techniques is employed in the second group. Follow-up is conducted in the first day, first week, and first month of the dacryocystorhinostomy which is followed by 4-month follow-up period, and results were compared using statistical methods. The main outcome measures were the elimination of epiphora and unrestricted flow of irrigated saline to the nose. Seven patients were male, 22 were female, and the mean age was 39.3 ± 12.5 years. Mean follow-up times were 111.3 ± 10.5 months and 93 ± 2.9 months in group 1 and group 2, respectively. Complete resolution is achieved in group 1, whereas failures stemming from canalicular stenosis and fibrosis at osteotomy site are recorded in two cases in group 2. Occlusion occurred in the fifth month in both cases. Thus, long-term success rates were 100% in the first and 86.6% in the second group (P = 0.483). MTE-DCR is a strong substitute for external DCR. Although TCML-DCR shows promising results, it is far away from becoming the gold standard technique in epiphora treatment.

Retro-orbital granuloma associated with granulomatosis with polyangiitis: a series of nine cases.

Retro-orbital granuloma is a rare and devastating component of granulomatosis with polyangiitis (GPA). Current medical treatment protocols are falling short, and outcomes are poor. The aim of the study was to investigate the frequency, clinical features, and treatment outcomes of retro-orbital granuloma in patients with GPA. This is a retrospective, multi-centre study, which involves GPA cohorts from five different clinics. Data were extracted from patient charts including history, physical examination, radiological-laboratory-histological findings, and treatment protocols. Major clinical outcome measures were changes in the volume of the granuloma on comparative MRI, and visual acuity on repeated ophthalmologic examinations. Among 141 GPA patients, nine (five females and four males) were diagnosed with a retro-orbital granuloma. Median duration of disease was 8 years. Proptosis and diplopia were the dominant presenting symptoms (77%), followed by orbital pain (55%). Three out of nine patients had isolated retro-orbital granulomas, without other organ involvement of GPA. Five patients received conventional pulse steroid and pulse cyclophosphamide (CYC) as the first-line remission induction therapy. Four of these patients had progressive disease, and a regression in granuloma size was observed in one patient using this regimen. Two patients were already receiving immunosuppressants when they were diagnosed with retro-orbital granuloma. Six patients had been treated with RTX as the second-line remission induction therapy. None of these patients had progression following RTX therapy. Three patients underwent orbital decompression surgery. The indication for the decision for surgery was either progressive loss of vision or intractable pain. Standard first-line chemotherapy (CYC and steroids) was ineffective against retro-orbital granuloma associated with GPA. RTX could be an alternative in these cases. Surgical intervention may help to decrease the morbidity. Further prospective studies with greater patient numbers are needed to test the clinical efficiency of RTX as a first-line remission induction chemotherapy.

The Role of FOXP3 Polymorphisms in Graves' Disease with or without Ophthalmopathy in a Turkish Population.

Objectives: Forkhead box P3 (FOXP3) gene polymorphisms have been evaluated in many autoimmune diseases, including Graves' disease (GD), in different populations. However, those polymorphisms have not been analyzed in GD or Graves' ophthalmopathy (GO) in the Turkish population. In this study, we aimed to evaluate the frequency of FOXP3 polymorphisms in GD with or without ophthalmopathy in a Turkish population. Materials and Methods: The study included 100 patients with GO, 74 patients with GD without ophthalmopathy, and 100 age- and sex-matched healthy controls. In all study participants, rs3761547 (-3499 A/G), rs3761548 (-3279 C/A), and rs3761549 (-2383 C/T) single nucleotide polymorphisms (SNPs) were detected using the polymerase chain reaction-restriction fragment length polymorphism method. The chi-square test was used to evaluate genotype and allele frequencies. Odds ratios and 95% confidence intervals were calculated for genotype and allele risks. Results: In the patient group (including GD with or without ophthalmopathy), the rs3761548 AC and AA genotype and rs3761549 CT genotype were significantly more frequent than in the control group (all p<0.05). No genotypic and allelic differences were observed for rs3761547 between the patient and control groups (all p>0.05). There was no statistically significant difference between the GO and GD without ophthalmopathy groups concerning the allele and genotype frequencies of all three FOXP3 SNPs (all p>0.05). Conclusion: The AC and AA genotypes of rs3761548 (-3279) and CT genotype of rs3761549 (-2383 C/T) were shown to be possible risk factors for GD development in the Turkish population. However, none of the three SNPs was shown to be associated with the development of GO in patients with GD.

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.

Clinical and radiologic outcomes of pleomorphic adenoma and adenoid cystic carcinoma of the lacrimal gland.

PURPOSE: To compare the radiologic and clinical features of primary lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma. METHODS: This study retrospectively reviewed imaging findings and medical records of lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma. RESULTS: Eleven patients with pleomorphic adenoma and 16 patients with adenoid cystic carcinoma were evaluated. There were no statistically significant differences between groups regarding age or sex. Proptosis was the most common presenting symptom in both groups. Adenoid cystic carcinomas were more likely to present with a palpable mass, diplopia, pain, and sensory loss than pleomorphic adenomas, although the differences were not statistically significant between groups. Furthermore, there were no significant differences in terms of homogeneity and globe indentation between lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma on computed tomography (CT)(all p>0.05). The rates of bone invasion, tumor calcification, and wedge sign were significantly higher in adenoid cystic carcinomas, and bone remodeling was statistically significantly higher in pleomorphic adenomas, on CT(all p<0.05). Pleomorphic adenomas were significantly more likely to show well-defined margins, lobulated contours, heterogeneous contrast enhancement, and hyperintensity on T2-weighted magnetic resonance images (all p<0.05). CONCLUSION: When differentiating between lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma, evaluation of radiologic features along with clinical features is of great importance. Lobulated contours may be a significant distinguishing radiologic feature suggesting pleomorphic adenoma.

Traumatic Dislocation of the Globe into the Ethmoid Sinus

Traumatic globe dislocation into the paranasal sinuses is a rare condition. Globe displacement with preserved integrity can result in functional and cosmetic recovery with rapid and appropriate intervention. In this article, we discuss the presentation and treatment of globe dislocation into the ethmoid sinus in a 36-year-old patient who presented to the emergency department with the complaint of vision loss due to a fall.

Unsuccessful lacrimal surgery: causative factors and results of surgical management in a tertiary referral center.

BACKGROUND: To evaluate possible causative factors of unsuccessful dacryocystorhinostomy (DCR) surgery, and present the surgical technique and results of revision external DCR in a tertiary referral center. METHODS: During 2001-2007, 79 patients (59 female, 20 male, 83 revised DCR sites) underwent revision external DCR for the management of recurrent epiphora after unsuccessful DCR surgery. The possible reasons for unsuccessful DCR surgery were noted according to the preoperative nasal endoscopic and perioperative findings, and revision surgery was performed to address these. RESULTS: The mean age was 43.1 ± 12.0 years, and the mean follow-up was 21.4 ± 12.4 months. At presentation, 58 patients had a history of 1 unsuccessful lacrimal surgery, 16 had 2 unsuccessful surgeries, and 5 had 3 unsuccessful surgeries. The most common preoperative endoscopic finding was nasal mucosal fibrosis and synechiae, and the most common causes of unsuccessful DCR surgery were inappropriate size and location of the bony ostium, fibrosis at rhinostomy site, and canalicular obstruction, respectively. Of the 83 revised DCR sites, 79 sites underwent external DCR with silicone intubation, and conjunctival DCR with Jones tube insertion was performed in 4 sites. Success was achieved in 78 sites (93.9%) with the first revision DCR surgery, and in 81 sites (97.6%) with the second revision. CONCLUSIONS: Revision DCR has standard concepts in common with primary DCR surgery; however, for a favorable surgical outcome, the revision surgery should address possible causative factors of failure.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the lacrimal drainage system in two pediatric patients.

Primary non-Hodgkin lymphoma (NHL) of lacrimal drainage system (LDS) is quite rare in children, but it is important to expedite early diagnosis in an effort to alter possible life-threatening disease since they are usually misdiagnosed as chronic dacryocystitis. In the literature, there are few examples of tumors of LDS in children. The authors herein report two pediatric cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) originating from lacrimal sac in an attempt to increase the knowledge about the clinical course of NHL of LDS. Considerable care must be taken since tumors of lacrimal drainage can mimic dacryocystitis clinically and macroscopically. Two patients both attended with painless swelling in the left lacrimal sac region and epiphora of the left eye. Orbital magnetic resonance imaging showed a tumoral lesion in the left lacrimal sac region and histopathological examination of excisional biopsy specimen demonstrated MALT lymphoma in both patients. The treatment regimen comprises lacrimal sac excision within the tumor, canalicular dacryocystorhinostomy (DCR) with bicanalicular silicone intubation (BSI) combined with chemotherapy and regional radiotherapy in one case, whereas the second case received only radiotherapy after canalicular DCR with BSI. Both of them maintained clinical remission along follow-up.

Intraocular pressure and superior ophthalmic vein blood flow velocity in Graves' orbitopathy: relation with the clinical features.

BACKGROUND: The aim of this study is to evaluate the association of intraocular pressure (IOP) and superior ophthalmic vein blood flow velocity (SOV-BFV) with the clinical features of Graves' orbitopathy. METHODS: During the 2002-2007 period, 66 eyes of 34 Graves' orbitopathy cases were classified as mild, moderate and severe orbital disease, and evaluated according to their clinical features as: i)type 1 vs type 2 cases, and ii) cases with or without dysthyroid optic neuropathy. In all patients, a full ophthalmic examination including IOP and Hertel measurements was performed. SOV-BFV was analyzed with color Doppler sonography. RESULTS: The Hertel value, IOP in primary and upgaze position were higher, and SOV-BFV was lower in moderate and severe Graves' orbitopathy cases that showed statistical significance from mild cases, and controls (p = 0.001). Moderate and severe Graves' orbitopathy cases showed comparable Hertel measures and IOP in primary and upgaze position (p = 0.39); however, SOV-BFV was significantly lower in severe cases when compared to moderate cases (p = 0.001).This study demonstrated statistically significant negative correlation between IOP in both primary (r = 0.43,p = 0.008) and upgaze position (r = 0.51,p = 0.002), and SOV-BFV. Additionally, statistically significant positive correlation was detected between Hertel values and SOV-BFV(r = 0.402,p = 0.007).There was a statistical difference between type 1 and 2 cases in Hertel values(p = 0.006), IOP in upgaze position (p = 0.026) and SOV-BFV (p = 0.003). SOV-BFV of the eyes showing dysthyroid optic neuropathy was statistically lower than eyes without dysthyroid optic neuropathy (p = 0.006). CONCLUSIONS: IOP and SOV-BFV have significant association with the clinical features of Graves' orbitopathy. The decrease in SOV-BFV increases the severity of Graves' orbitopathy, and may have a role in the clinical course of dysthyroid optic neuropathy.

Orbital cyst of lacrimal derivation presenting as a recurrent orbital abscess in a pediatric patient.

A 2-year-old girl presented with inflammatory eyelid swelling in the left eye over a 2-week period. Ophthalmologic examination showed hyperemia and swelling, with a palpable mass at the inferior orbital rim. Orbital magnetic resonance imaging showed periorbital edema and a cystic lesion located in the inferomedial orbit. Histopathologic evaluation showed an orbital cyst of lacrimal derivation.

Long-term success rate of perforated punctal plugs in the management of acquired punctal stenosis.

PURPOSE: To give the long-term success rates of punctal dilatation with insertion of perforated punctal plugs (PPP) for the management of acquired punctal stenosis. METHODS: A series of 44 eyes of 26 patients who underwent PPP implantation for the management of acquired punctal stenosis were retrospectively evaluated in terms of the severity of acquired punctal stenosis, associated eyelid disorders, implantation technique of PPP, and long-term success rate of PPP for the treatment of epiphora. In all patients, punctal dilation was performed prior to the insertion of plugs. Patients demonstrating moderate or severe horizontal eyelid laxity underwent a lateral tarsal strip procedure before PPP implantation. Complete stenosis of the punctum was treated with the radiofrequency unit before PPP implantation. The plugs were extracted at 2 months in every patient. RESULTS: The mean age of the patients was 63.6 +/- 10.5 years. The median interval between the onset of epiphora and PPP implantation was 15 months. There were 14 complete stenoses, 29 partial punctal stenoses, and 1 squamous papilloma involving the inferior punctum causing epiphora. Associated eyelid laxity was detected in 14 of 44 eyes (31.8%), and 8 eyes underwent a lateral tarsal strip procedure before PPP implantation. The mean follow-up time was 19.0 +/- 13.4 months. Success was achieved in 37 of 44 eyes (84.1%), with relief of epiphora. Of the 7 eyes with continued epiphora, 3 eyes demonstrated recurrent punctal stenosis and 4 eyes demonstrated mild horizontal eyelid laxity. CONCLUSIONS: The long-term success rate of PPP implantation for the treatment of acquired punctal stenosis is satisfactory. Associated eyelid pathologies should be evaluated for their contribution to epiphora and be treated before PPP implantation.

Orbital decompression surgery for the treatment of Graves' ophthalmopathy: comparison of different techniques and long-term results.

AIM: To evaluate the long-term results of different orbital decompression techniques performed in patients with Graves' ophthalmopathy (GO). METHODS: Totally 170 cases with GO underwent orbital decompression between 1994 and 2014. Patients were divided into 4 groups as medial-inferior, medial-lateral (balanced), medial-lateral-inferior, and lateral only according to the applied surgical technique. Surgical indications, regression degrees on Hertel exophthalmometer, new-onset diplopia in the primary gaze and new-onset gaze-evoked diplopia after surgery and visual acuity in cases with dysthyroid optic neuropathy (DON) were compared between different surgical techniques. RESULTS: The study included 248 eyes of 149 patients. The mean age for surgery was 42.3±13.2y. DON was the surgical indication in 36.6% of cases, and three-wall decompression was the most preferred technique in these cases. All types of surgery significantly decrease the Hertel values (P<0.005). Balanced medial-lateral, and only lateral wall decompression caused the lowest rate of postoperative new-onset diplopia in primary gaze. The improvement of visual acuity in patients with DON did not significantly differ between the groups (P=0.181). CONCLUSION: The study show that orbital decompression surgery has safe and effective long term results for functional and cosmetic rehabilitation of GO. It significantly reduces Hertel measurements in disfiguring proptosis and improves visual functions especially in DON cases.

Clinical and radiologic outcomes of pleomorphic adenoma and adenoid cystic carcinoma of the lacrimal gland / Desfechos clínicos e radiológicos do adenoma pleomórfico e do carcinoma adenoide cístico da glândula lacrimal

ABSTRACT Purpose: To compare the radiologic and clinical features of primary lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma. Methods: This study retrospectively reviewed imaging findings and medical records of lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma. Results: Eleven patients with pleomorphic adenoma and 16 patients with adenoid cystic carcinoma were evaluated. There were no statistically significant differences between groups regarding age or sex. Proptosis was the most common presenting symptom in both groups. Adenoid cystic carcinomas were more likely to present with a palpable mass, diplopia, pain, and sensory loss than pleomorphic adenomas, although the differences were not statistically significant between groups. Furthermore, there were no significant differences in terms of homogeneity and globe indentation between lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma on computed tomography (CT)(all p>0.05). The rates of bone invasion, tumor calcification, and wedge sign were significantly higher in adenoid cystic carcinomas, and bone remodeling was statistically significantly higher in pleomorphic adenomas, on CT(all p<0.05). Pleomorphic adenomas were significantly more likely to show well-defined margins, lobulated contours, heterogeneous contrast enhancement, and hyperintensity on T2-weighted magnetic resonance images (all p<0.05). Conclusion: When differentiating between lacrimal gland pleomorphic adenoma and adenoid cystic carcinoma, evaluation of radiologic features along with clinical features is of great importance. Lobulated contours may be a significant distinguishing radiologic feature suggesting pleomorphic adenoma.

RESUMO Objetivo: Comparar as características radiológicas e clínicas do adenoma pleomórfico primário e do carcinoma adenoide cístico da glândula lacrimal. Métodos: Este estudo revisou retrospectivamente os achados de imagem e os prontuários médicos de casos de adenoma pleomórfico e carcinoma adenoide cístico da glândula lacrimal. Resultados: Foram avaliados 11 pacientes com adenoma pleomórfico e 16 pacientes com carcinoma adenoide cístico. Não houve diferenças estatisticamente significativas em relação à idade e sexo. Proptose foi o sintoma de apresentação mais comum em ambos os grupos. Os carcinomas adenoides císticos foram mais propensos que os adenomas pleomórficos a apresentarem massas palpáveis, diplopia, dor e perda sensorial, mas essa diferença entre os grupos não foi estatisticamente significativa. Não houve diferenças estatísticas em termos de homogeneidade e indentação do globo ocular entre os dois tipos de tumores em imagens de tomografia computadorizada (p>0,05). Também à tomografia computadorizada, a invasão óssea, a calcificação do tumor e o sinal em cunha foram mais frequentes nos carcinomas adenoides císticos, enquanto a remodelação óssea foi mais frequente nos adenomas pleomórficos, com significância estatística para todas essas manifestações (p<0,05). À ressonância magnética, os adenomas pleomórficos foram significativamente mais propensos a terem margens bem definidas, contornos lobulados, realce heterogêneo pelo contraste e hiperintensidade na ressonância magnética ponderada em T2 (p<0,05). Conclusão: Ao se diferenciar o adenoma pleomórfico e o carcinoma adenoide cístico da glândula lacrimal, é muito importante avaliar as características radiológicas juntamente com as características clínicas. Os contornos lobulados podem ser uma característica radiológica significativamente distinta em favor do adenoma pleomórfico.

Predictive score for the development or progression of Graves' orbitopathy in patients with newly diagnosed Graves' hyperthyroidism.

OBJECTIVE: To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). DESIGN: Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. METHODS: 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. RESULTS: GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2-10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91 (95% CI 0.87-0.94) respectively. CONCLUSIONS: In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

Apoptosis in orbital fibroadipose tissue and its association with clinical features in Graves' ophthalmopathy.

PURPOSE: To evaluate the rate of apoptosis in orbital fibroadipose tissue in Graves' ophthalmopathy (GO) patients and investigate its associations with disease characteristics. METHODS: Orbital tissue samples were obtained during decompression surgery from 25 GO patients. Disease activity was evaluated using the Clinical Activity Score, while the clinical features of GO were evaluated using the Total Eye Score (TES). Tissue samples of 12 patients without any thyroid or autoimmune disease were studied as controls. The rate of apoptosis was evaluated with a terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay, and ultrastructural features of apoptosis were evaluated with electron microscopy. RESULTS: The rate of apoptosis in orbital fibroadipose tissue was significantly higher in GO cases than in the control group (p < 0.001) and significantly correlated with TES (r: 0.545; p = 0.005). The rate of apoptosis was 7.9% +/- 6.5%, and 22.0% +/- 7.8% in type 1 and type 2 cases, respectively (p = 0.001). The rate of apoptosis was 21.6% +/- 7.5% in eyes showing dysthyroid optic neuropathy (DON) and 6.7% +/- 5.4% in eyes without DON (p = 0.005). CONCLUSIONS: The rate of apoptosis was high in the orbital fibroadipose tissue of GO cases and was related to the clinical features of the disease.

A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy.

Mulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal onset severe growth retardation and pericardial constriction associated with abnormalities of muscle, liver, brain and eye. More than 80% of previously reported patients are of Finnish origin in whom a founder mutation in the TRIM37 gene have been described. We report on a 7-year-old Turkish boy who presented with classical phenotypic features of mulibrey nanism. Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c.1894_1895delGA, resulting in a frame-shift and a premature termination codon. Our proband is one of the rare examples of mulibrey nanism outside Finland and extends the mutation spectrum in this disorder.

Expression of cyclooxygenase-2 in orbital fibroadipose connective tissues of Graves' ophthalmopathy patients.

OBJECTIVE: The aim of this study is to evaluate the expression of cycloocygenase-2 (COX-2) in orbital fibroadipose connective tissue in Graves' ophthalmopathy (GO) patients, and investigate the associations between COX-2 expression and GO characteristics. METHODS: The orbital fibroadipose connective tissues of 23 cases demonstrating moderate or severe GO, and eight control subjects without any history of thyroid or autoimmune disease were analyzed for COX-2 mRNA expression. Real-time relative quantitative PCR was performed to assess transcripts of COX-2 using the LightCycler. The disease activity was evaluated by the clinical activity score (CAS). The clinical features of GO were evaluated by total eye score (TES) and the cases were divided into two groups; type 1 cases included higher degrees of proptosis with orbital fat volume increase, and type 2 cases included cases with compressive neuropathy and limited extraocular muscle functions. RESULTS: The mean +/- s.d. disease duration was 5.7 +/- 7.1 years. The mean +/- s.d. CAS and TES of cases were 1.60 +/- 1.04 and 7.5 +/- 1.8 respectively. The mean +/- s.d. expression of COX-2 was 0.023 +/- 0.013 and 0.010 +/- 0.002 in GO cases and controls (P = 0.008), and 0.015 +/- 0.073 and 0.029 +/- 0.135 in type 1 and type 2 cases respectively (P = 0.007). COX-2 expression showed a statistically significant positive correlation with TES (r = 0.634, P = 0.001), and a negative correlation with the disease duration (r = -0.621, P = 0.002). CONCLUSIONS: COX-2 is expressed at higher levels in orbital fibroadipose tissues of GO cases. This showed a positive correlation with increasing severity of orbital disease suggesting possible relation with COX-2 expression and orbital inflammation in GO.

Surgical Treatment of Dysthyroid Optic Neuropathy: Long-Term Visual Outcomes with Comparison of 2-Wall versus 3-Wall Orbital Decompression.

PURPOSE: To compare the long-term visual outcomes after 2-wall (medial-lateral) versus 3-wall (medial-lateral-inferior) orbital decompression combined with fat removal in patients with dysthyroid optic neuropathy (DON). METHODS: Records of 68 eyes of 42 patients were retrospectively reviewed. Two-and 3-wall decompression was performed in 41 and 27 eyes, respectively. Transcaruncular approach was used for medial wall decompression. Lateral canthotomy combined with upper eyelid crease incision was used for lateral wall removal, and combined with transconjunctival lower eyelid incision if floor decompression performed. Outcome measures were visual acuity (VA), color vision, Hertel measures, visual field mean deviation (MD) and pattern standard deviation (PSD) Result: The mean follow-up time was 39.3 months (range, 12-72 months). All indicators of visual function significantly improved after 2-and 3-wall decompression. The improvement in VA and color vision was similar between groups. (logMAR VA: 2-wall: 0.52 ± 0.68 versus 3-wall: 0.71 ± 0.86, p = 0.335); (color vision on Ishihara plates: 2-wall: 10.1 ± 8.1 versus 3-wall: 11.6 ± 7.8, p = 0.447). The improvement in MD and PSD were higher after 3-wall decompression (MD: 2-wall: 10.0 ± 5.5 versus 3-wall: 14.3 ± 7.5 dB, p = 0.020); (PSD: 2-wall: 3.5 ± 1.9 versus 3-wall: 4.8 ± 3.0 dB, p = 0.045). Proptosis reduction was higher after 3-wall decompression (2-wall: 5.1 ± 1.3 versus 3-wall: 7.2 ± 1.9 mm, p = 0.0001). New onset diplopia was seen 20% and 28.5% of cases in 2-and 3-wall decompression, respectively. No adnexal/orbital complications were seen in 2-wall group, however orbital hematoma (1 case) and persisting eyelid edema (1 case) were encountered in 3-wall group. CONCLUSION: Both 2-and 3-wall orbital decompressions are safe and effective for management of visual dysfunction in DON. Although 3-wall decompression provide better improvement in the parameters of visual field analysis and Hertel measures, new onset diplopia, adnexal/orbital complications are more common with this technique.