Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

Sight-Threatening Graves' Ophthalmopathy during the Third Trimester of Pregnancy: A Case Report.

Dysthyroid optic neuropathy is a severe manifestation of Graves' ophthalmopathy that can result in permanent vision loss. We report a 37-year-old pregnant woman with Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy in the third trimester of pregnancy. Diplopia, bilateral eye lid retraction, lid edema and proptosis were observed in the 29th week of gestation. Thyroid-stimulating hormone (TSH) level was decreased with a normal level of free triiodothyronine (FT3) and an upper normal level of free thyroxine (FT4). Anti-TSH receptor antibodies (16.2 IU/L, reference range < 2.0 IU/L) and thyroid stimulating antibody (4,443%, reference range < 120%) were positive. Magnetic resonance imaging (MRI) demonstrated a significant enlargement of the extraocular muscles with a high signal intensity on T2-weighted image. She was diagnosed as Graves' ophthalmopathy and subclinical hyperthyroidism, and followed without treatment. In the 34th week of gestation, the symptom of color vision abnormality appeared, suggesting dysthyroid optic neuropathy. She delivered a female infant during the 36th week of gestation. Four days after delivery, she had a spontaneous orbital pain. MRI showed that the extraocular muscles were more enlarged than the findings in the 29th week of gestation. FT3 and FT4 levels were mildly elevated. Dysthyroid optic neuropathy was diagnosed. She was treated with methylprednisolone pulse therapy and retrobulbar injections of betamethasone valerate, and the ocular symptoms improved. The present case shows that the glucocorticoid therapy performed one week after delivery is effective against Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy during the third trimester of pregnancy.

[Dysthyroid optic neuropathy in pregnancy].

BACKGROUND: While development of thyroid eye disease is rarely observed in pregnant women, here we report three cases of pregnant patients with severe dysthyroid optic neuropathy (DON). CASE: Case 1, a 30 year-old woman with thyroid eye disease diagnosed during pregnancy and DON occurring at eight months. Visual acuity was 0.05 in right eye and 0.8 in left. Case 2, a 32 year-old woman with Graves' disease diagnosed during pregnancy and DON occurring at five months. Visual acuity was 0.2 in right eye and 0.09 in left. In cases 1 and 2, since no permission for therapy during pregnancy was obtained from either patient, systemic steroid therapy was performed after delivery. Case 3, a 31 year-old woman with Graves' disease diagnosed during pregnancy. At nine months, DON was diagnosed in both eyes. Visual acuity was 0.07 in right eye and 0.2 in left. An organized systemic steroid therapy following delivery at the end of a normal gestational period was performed. In all three patients, higher levels of thyroid antibodies were observed while thyroid function remained controlled. CONCLUSION: DON developed in pregnant woman with Graves' disease who have higher levels of thyroid antibodies. A close coordination between internists and obstetricians is required for appropriate treatment, including systemic steroid therapy.

Proptosis in dysthyroid ophthalmopathy: a case series of 10,931 Japanese cases.

PURPOSE: This observational case series investigated the occurrence and distribution of proptosis in Japanese patients with dysthyroid ophthalmopathy (DO). The relationship among lid retraction, lid swelling, and enlargement of extraocular muscles was also analyzed. METHODS: From 1993 to 2002, 10 931 patients (2240 men and 8691 women, average age; 39.9 ± 14.0 years) with abnormal thyroid function were examined for proptosis. Proptosis was measured using a Hertel exophthalmometer, and lid swelling and retraction were classified. Orbital magnetic resonance imaging or computed tomography was used to quantify enlargement of the extraocular muscles. RESULTS: Clinically significant proptosis (≥15 mm) was present in 74.2% patients and was classified as mild (15-17 mm, 39.1%), moderate (18-20 mm, 25.9%), or severe (>20 mm, 9.2%). The average exophthalmometer reading was 17.2 ± 3.2 mm, with proptosis less pronounced with age (p < 0.001) and more pronounced in men than women (18.2 ± 3.4 mm vs. 17.0 ± 3.1 mm; p < 0.001). Lid retraction was present in 57.7% of patients, lid swelling in 46.9%, and muscle enlargement in 40.8% of patients. Multiple regression analysis revealed proptosis was strongly correlated with a young age and the male gender, followed by extraocular muscle enlargement and lid retraction and swelling (p < 0.001). CONCLUSIONS: This study assessed the measurable features of proptosis in Japanese patients with DO and contributes to the understanding by correlating symptoms and signs of DO.

[Cytotoxicity of antiglaucoma ophthalmic solutions for human corneal endothelial cells].

PURPOSE: The cytotoxicity of a range of commercial antiglaucoma ophthalmic solutions was assessed in human corneal endothelial cells using in vitro techniques. METHODS: Cell survival was measured using the WST-1 assay for endothelial cells and the MTT assay for epithelial cells. Commercially available timolol, carteolol, latanoplast, unoprostone, levobunolol, bunazosine, betaxolol, nipradiol, dorzolamide, brinzolamide, and pilocarpine were assessed. The survival of cells exposed to test ophthalmic solutions was expressed as a percentage of cell survival in the control solution (distilled water added to media) after 48 hours exposure. RESULTS: Survival was lower in prostagrandines and in medications containing benzalkonium. It increased to more than 85% after dilution of 1000-fold or more dilution. CONCLUSIONS: Antiglaucoma ophthalmic solutions have corneal endothelial toxicity. The toxicity significantly decreases after dilution of 1000-fold or more dilution and toxicity seems to be due mostly to benzalkonium chloride.

Clinical efficacy of transcutaneous triamcinolone acetonide injection for upper eyelid retraction and swelling in patients with thyroid eye disease.

AIM: To evaluate the efficacy of transcutaneous triamcinolone acetonide (TA) injection for the treatment of upper eyelid retraction and swelling in thyroid eye disease (TED) patients. PATIENTS AND METHODS: This is a case series. Three euthyroid TED patients with features of both upper eyelid retraction and swelling were recruited. TED signs appeared within 6 months prior to treatment. Next, 0.5 mL of TA (40 mg/mL) was transcutaneously injected targeting the orbital fat around the levator palpebrae superioris (LPS) muscle. At each visit, eyelid retraction was evaluated by palpebral fissure height and the presence of scleral show above the superior corneoscleral limbus. Eyelid swelling was judged by the appearance of upper eyelid bulging and the lack of an eyelid sulcus. In addition, the LPS muscle, orbital and retro-orbicularis oculi fat were observed using MRI before and after treatment. RESULTS: Two patients had resolution of their upper lid retraction and swelling within 12 months. In the other patient who had proptosis, eyelid retraction resolved, while eyelid swelling remained mild. In all cases, MRI revealed that treatment resulted in thinner LPS muscle and reduced fat swelling. In addition, both high-intensity signals on T2 images and prolonged T2 relaxation time were normalized. No adverse signs were observed. CONCLUSION: Transcutaneous TA injection was effective as a treatment for upper eyelid retraction and swelling in euthyroid TED patients who had signs within 6 months prior to treatment. Transcutaneous TA injection induced reduction of LPS muscle enlargement and fat tissue swelling. These reductions by transcutaneous TA injection were verified using MRI.

Clinical course of thyroid function and thyroid associated-ophthalmopathy in patients with euthyroid Graves' disease.

BACKGROUND: Euthyroid Graves' disease (EGD) is a rare condition defined as the presence of thyroid-associated ophthalmopathy (TAO) in patients with normal thyroid function. Due to the rarity of this disease, only a limited number of studies and case reports are available for further evaluation of the characteristics of the disease. The aim of this study was to examine the changes in the thyroid function, thyrotropin receptor antibodies (TRAb) and eye symptoms, and then determine whether TRAb is related to TAO in EGD patients. TRAb in this study was defined as including both thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSAb). PATIENTS AND METHODS: Medical records of patients diagnosed with EGD were reviewed. Ophthalmologists specializing in TAO examined the eyes of all subjects. RESULTS: Of the 58 patients diagnosed with EGD, 24.1% developed hyperthyroidism, while 3.4% developed hypothyroidism. A total of 72.4% of the 58 patients remained euthyroid throughout the entire follow-up period. At the initial presentation, TBII and TSAb were positive in 74.5% and 70.5%, respectively. Ophthalmic treatments were administered to 30 (51.7%) out of the 58 patients. A significant spontaneous improvement of the eye symptoms was found in 28 of the EGD patients who did not require eye treatments. EGD patients exhibited positive rates for both TBII and TSAb, with the number of the TRAb-positive patients gradually decreasing while the eye symptoms spontaneously improved over time. There were no correlations found between TRAb at initial presentation and the eye symptoms. CONCLUSION: TBII and TSAb were positive in about 70% of EGD patients at their initial visit. Thyroid functions of EGD patients who have been euthyroid for more than 6.7 years may continue to remain euthyroid in the future.

Pathological Findings of the Thyroid Tissue in a Patient with Euthyroid Graves' Disease.

Euthyroid Graves' disease (EGD) is a rare condition marked by the onset of thyroid-associated ophthalmopathy (TAO) in the absence of thyroid dysfunction. The pathogenesis of EGD remains unclear, and a consistent view of the pathological findings of the thyroid tissue has yet to be determined. We herein report a case of EGD in a 34-year-old woman with papillary carcinoma treated with total thyroidectomy. The entire thyroid specimen was investigated, and the thyroid tissue appeared normal. In this report, we discuss the relationship between the pathogenesis of TAO and thyroid dysfunction.

A characteristic optic disc appearance associated with myopia in subjects with Graves' ophthalmopathy and in subjects with primary open-angle glaucoma.

PURPOSE: To determine if qualitatively defining the appearance of optic disc change was a valid characteristic of myopia in subjects with Graves' ophthalmopathy (GO) or primary open-angle glaucoma (POAG). METHODS: WE DEFINED TYPICAL TILT APPEARANCE AS THE SIMULTANEOUS PRESENCE OF THE FOLLOWING: an elliptical optic disc, a crescent, unequal sharpness of the cupping margin (horizontally), and nasally displaced vessels in the optic cup. Ninety-two eyes from 92 subjects each with GO or with POAG and no severe complications were included in the study after matching for spherical refractive errors. Using our definition of tilt appearance, two independent observers subjectively judged optic disc photographs. One observer repeated judgments in 70 randomly selected eyes and judgment reproducibility was assessed using kappa statistics. Tilt ratio was used as a quantitative parameter. RESULTS: The numbers of eyes judged as having a typical tilt appearance in the GO group and in the POAG group were 25 (27.2%) and 39 (42.4%), respectively, by one observer (P = 0.0297), and 12 (13%) and 44 (47.8%), respectively, by another observer (P < 0.0001). Intra- and interobserver reproducibility of tilt judgment were very good (kappa = 0.93) and good (kappa = 0.65), respectively. Tilt ratio did not significantly differ between the two groups. Analytical results including background factors were essentially the same for the two observers: multivariate logistic regression for one observer's judgment showed that the presence of the typical tilt appearance was associated with belonging to the glaucoma group (odds ratio [OR], 6.25; P = 0.0054), tilt ratio (OR per 0.01, 0.77; P < 0.0001), and spherical refractive error (OR per diopter, 0.80; P < 0.003). CONCLUSION: The optic disc feature we designated as typical tilt was associated with myopia, and its frequency was higher in subjects with POAG compared to those with GO.