Borrelia Ocular Infection: A Case Report and a Systematic Review of Published Cases.

INTRODUCTION: Lyme borreliosis can cause many diverse manifestations, also ocular disease where the diagnosis of ocular borreliosis is challenging. The primary aim was to report on the evidence of Borrelia spirochetes in the ocular tissue in presumed ocular borreliosis. METHODS: A systematic review of pathological eye conditions was performed where Borrelia has been suspected in relevant ocular tissue, together with a case report of diagnosed uveitis with polymerase chain reaction (PCR)-confirmed Borrelia afzelii in the vitreous. The evidence for clinical and laboratory diagnosis was evaluated systematically. As a secondary aim, the treatment of ocular Borrelia infection was also evaluated for confirmed cases. RESULTS: Thirteen includable studies were found, and after the removal of case duplicates, eleven unique cases were extracted. Apart from the present case report, 4 other cases reported strong evidence for the detection of B. spirochetes in ocular tissue. Four cases presented reasonable evidence for assumed detected Borrelia, while three additional cases showed only weak diagnostic credibility that Borrelia was detected. CONCLUSION: This systematic review, including all reported cases and our case report, supports evidence of ocular infection of Borrelia species. Furthermore, in case of suspicion of infection and seronegativity, it is justified to look for Borrelia in eye tissue samples. In addition, microscopy without using PCR is not sufficient to confirm the diagnosis of borreliosis on ocular tissue. In the articles studied, there was no unambiguous recommendation of treatment.

Epidemiology of uveitis in a region of southern Sweden.

PURPOSE: To analyse the distribution and treatment of uveitis in a region of southern Sweden and compare the results with previously reported European data. METHODS: Anonymized data for all individuals in the region with an ICD-10 diagnosis that indicated uveitis between 2013 and 2017 were extracted from a computerized healthcare register. RESULTS: In total, 2483 patients were diagnosed with uveitis during 2013-2017. Anterior uveitis was diagnosed in 93%, intermediate in 1%, posterior in 5% and panuveitis in 1% of cases. An associated diagnosis was found in 14%, and the five most common associated diseases were herpes simplex/zoster (4.9%), inflammatory bowel disease (2.2%), rheumatic arthritis (1.9%), ankylosing spondylitis (1.8%) and sarcoidosis (1.8%). Systemic treatment was used in 14% of the cases. The period prevalence of uveitis was 700 cases per 100 000 individuals, and the yearly incidence was estimated to 108 cases/year/100 000 individuals. CONCLUSIONS: Compared with studies from referral clinics, this community-based study had a large proportion of anterior uveitis (93%) and uveitis without associated diagnosis (86%). Uveitis was also much more common among elderly than shown in previous research. The distribution of possible associated diagnosis conformed to several previous European studies.

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations.

BACKGROUND: Orbital morphological changes are often present in patients with Graves' disease (GD) already at diagnosis, and cyclooxygenase type 2 (COX-2) is overexpressed in active Graves' ophthalmopathy (GO). OBJECTIVE: To investigate if adjuvant treatment of GD with the COX inhibitor and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist diclofenac decreases the development of ophthalmopathy and if laboratory parameters are affected. METHODS: This is a multicenter trial where 61 subjects were randomized to methimazole (block and replace with l-thyroxine) either with or without diclofenac 50 mg 1 × 2 for 12 months. The primary end point development of GO after 24 months was evaluated. Smoking habits were registered and the thyroid parameters TSH, free T4, free T3, TSH receptor antibodies (TRAb) and anti-TPO were followed. Safety parameters (kidney, liver and blood) and adverse events were regularly registered. RESULTS: GO developed in 11% (n = 3) of the patients treated with diclofenac and in 21% (n = 6) of the controls (p = 0.273). The adverse event profile was acceptable without any severe events related to diclofenac. Both TRAb and anti-TPO concentrations decreased during treatment with methimazole, but the anti-TPO concentrations were lower in patients treated with diclofenac after 15 months (p = 0.031). The TRAb concentrations were not significantly changed between groups. Smokers had higher concentrations of TRAb than nonsmokers both at diagnosis of GD (p = 0.048) and after 15 months (p = 0.042). CONCLUSIONS: Treatment with diclofenac had no significant influence on development of GO. Diclofenac reduces anti-TPO concentrations and seems to be safe to use in GD patients.

Test-retest variation in macular thickness measurements with the Heidelberg Retina Tomograph.

PURPOSE: The aim was to evaluate the test-retest variation of macular thickness measurements using the Heidelberg Retina Tomograph (HRT3) Retina Module and compare it with the Stratus optical coherence tomography (OCT). As no normative data has been published for the HRT Retina Module, a secondary purpose was to obtain reference values for this technique. METHODS: Thirty healthy subjects and nine patients with macular oedema were examined. The healthy subjects underwent five examinations by two experienced examiners at two different occasions. The patients with maculopathy were examined twice by one examiner on one occasion. All measurements were made with both the HRT3 and the Stratus OCT and the macular thickness measurements were used for calculations of the test-retest variation. RESULTS: In healthy subjects the coefficient of variation (CV) ranged from 4.5 to 8.8 per cent with the HRT3 and from 0.6 to 1.5 per cent with the Stratus OCT. In the nine patients with macular oedema, the HRT CV ranged from 7.9 to16.6 per cent and for OCT from 1.1 to 2.5 per cent. The intra-class correlation in the central area for intra-observer/intra-visit in healthy subjects was 0.78 with the HRT3 and 0.93 with the Stratus OCT. Corresponding values for the patients with macular oedema were 0.64 with the HRT3 and 1.0 with the Stratus OCT. Mean macular thickness was significantly larger in all areas measured with the HRT3 compared with the Stratus OCT. No significant correlations were found between the thickness values from the different instruments. CONCLUSION: In this study, macular thickness was measured with two different techniques. The HRT3 showed lower repeatability and reproducibility as well as a higher CV compared with the Stratus OCT in both healthy subjects and patients with macular oedema. This difference might be of clinical relevance, even though the nine patients with maculopathy in the current study showed abnormal results with both methods.

Increased risk of uveitis in coeliac disease: a nationwide cohort study.

BACKGROUND: Case reports suggest a potential association between coeliac disease (CD) and uveitis, but larger well-controlled studies are lacking. The aim of this study was therefore to examine the risk of uveitis in patients with biopsy-verified CD. METHODS: Small intestinal biopsy reports performed between July 1969 and February 2008 were collected from all (n=28) pathology departments in Sweden. From these reports, 29,044 patients with CD (equals villous atrophy, Marsh 3) were identified. Uveitis was defined according to relevant International Classification of Disease codes in the Swedish National Patient Register. Cox regression was used to estimate HR for uveitis in individuals with CD compared with those in reference individuals matched for age, sex, county and calendar year. RESULTS: During follow-up, 148 patients with CD developed uveitis (expected count 112), corresponding to a HR of 1.32 (95% CI 1.10 to 1.58). The absolute risk of uveitis was 50/100,000 person-years in CD. The risk estimate did not change more than marginally when adjusted for type 1 diabetes, rheumatoid arthritis and autoimmune thyroid disease (HR 1.30; 95% CI 1.08 to 1.56). The risk of uveitis remained significantly increased even 5 years after CD diagnosis (HR 1.31; 95% CI 1.04 to 1.64). CONCLUSION: A moderately increased risk of uveitis was found in patients with biopsy-verified CD. CD might be considered in patients with uveitis of unknown aetiology.

Changes of saccadic eye movements in thyroid-associated ophthalmopathy.

PURPOSE: To establish whether or not the dynamics of saccadic eye movements are significantly changed in patients with different stages of thyroid-associated ophthalmopathy (TAO) and, subsequently, if analysis of saccades could serve as an additional diagnostic tool for early detection of inflammatory activity in TAO. METHODS: Thirty-seven patients with TAO and 10 age- and gender-matched control subjects were investigated. The patients were divided into four groups according to the stage of the disease: (i) early mild disease (n = 10), (ii) early severe disease (n = 11), (iii) long-standing restrictive disease (n = 10) and (iv) proven auto-immune hyperthyroidism without any signs of TAO (n = 6). Horizontal and vertical saccades with amplitudes of 10°, 20°, 30° and 40° were recorded binocularly using the induction scleral search coil technique. The two main sequence constants V(max) and C were calculated for each eye. Repeated measurement analysis of variance was carried out to test for differences between different gaze directions, eyes and groups. RESULTS: In horizontal saccades, significant differences were found between groups but not between abduction and adduction. In vertical saccades, differences between groups and the interaction between groups and up- and down-gaze saccades were significant. Compared with the control group, analysis of the main sequence curves revealed larger differences in patients of group 3 and 4 than in those of group 1 and 2. Whereas in the control group down-gaze saccades were faster than up-gaze saccades, the opposite behaviour was found in all patient groups. The largest differences were detected among those patients who had no signs of TAO (group 4). CONCLUSIONS: In this study, significant saccade differences were detected in all patients with TAO. In contrast to our earlier studies where evaluation of multiple individual saccade parameters did not reveal significant differences, analysis of the main sequence constants and mathematical reconstruction of the main sequence curves turned out to be a sensitive technique for reliable detection of subtle ocular motility changes. Significant differences were detected even in patients with auto-immune thyroiditis where no clinical signs of TAO were apparent.

Thyroid-associated ophthalmopathy after treatment for Graves' hyperthyroidism with antithyroid drugs or iodine-131.

CONTEXT: Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO). OBJECTIVES: The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs. DESIGN: We conducted a randomized trial (TT 96) with a follow-up of 4 yr. PATIENTS, SETTING, AND INTERVENTION: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T(4) was given in both groups. MAIN OUTCOME MEASURE: Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001). RESULTS: The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism. CONCLUSIONS: Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.

TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study.

INTRODUCTION: Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. OBJECTIVE: To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity. METHODS: Patients with newly diagnosed Graves' hyperthyroidism aged 20-55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients > or = 35 years of age). L-thyroxine (L-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. RESULTS: Medical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70-80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. CONCLUSION: The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

Magnetic resonance imaging and ultrasound measurements of extraocular muscles in thyroid-associated ophthalmopathy at different stages of the disease.

PURPOSE: To assess extraocular muscle (EOM) involvement in thyroid-associated orbitopathy (TAO) of different stages with magnetic resonance imaging (MRI) and ultrasound techniques. METHODS: A total of 32 patients with TAO were divided into three groups according to whether they had mild active, pronounced active or longstanding inactive disease. Six patients with Graves' disease but no clinical signs of TAO and 10 healthy control subjects were also studied. Muscle volume and cross-sectional area were measured with MRI. A-scan ultrasound was used to measure muscle thickness. RESULTS: The average MRI volume and maximal cross-sectional area of the EOM were significantly larger in patients with pronounced active and longstanding inactive TAO than in control subjects. Increased average muscle thickness measured by ultrasound was found mainly in patients with longstanding disease. Muscle enlargement was seen with MRI and ultrasound in individual patients in all patient groups, including those with Graves' disease but no TAO. Bilateral muscle enlargement was revealed by MRI in about two-thirds of patients with mild active TAO and in all patients with pronounced active and longstanding inactive TAO. Bilateral involvement estimated with ultrasound was less common in all patient groups. The MRI and ultrasound findings were not well correlated in any patient group. CONCLUSIONS: Extraocular muscle enlargement was seen in all patient groups with TAO of differing levels of severity. Measurements with MRI of muscle volume or maximal cross-sectional area are considered good indicators of muscle enlargement in TAO.

Graves' disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery.

The effects of treatment modality for Graves' disease (GD) were studied with respect to long-term quality of life and present health status. A total of 179 patients with GD were randomized during the period 1983-1990 for treatment with antithyroid drugs, radioiodine, or surgery. A 36-item Short Form Health Status Survey questionnaire and specific questions for GD were sent to patients 14-21 years after randomization. Present medical records, and clinical and laboratory status were recorded. No major significant differences in quality of life among the three treatments were observed. Compared to a large Swedish reference group, all treatment groups had significantly lower scores for vitality (p < 0.05). The Mental Component Summary was lower for both the young medical, young surgical, and the older medical group (p < 0.05). Radioiodine-treated patients had a lower General Health score. Young medical patients (<35 years) had lower Mental Health scores (p < 0.05). There was also a strong trend, which barely met statistically significance, for older surgical and radioiodine groups for lower Mental Component Summary. GD patients have, compared with a large Swedish reference population, diminished vital and mental quality of life aspects even many years after treatment. The quality-of-life scores were not different among the three treatment modalities.

Eye muscle force development and saccadic velocity in thyroid-associated ophthalmopathy.

BACKGROUND: Ocular motility disturbances are very common in patients with thyroid-associated ophthalmopathy (TAO). The force duction test has demonstrated that limitations of eye movements may be caused by mechanical restrictions in the muscles. A quantitative evaluation of isometric force production and ocular motility in all directions of gaze could further elucidate the mechanism of the movement disorder. METHODS: In eight patients with TAO and eight controls of the same age range, horizontal and vertical saccadic movements of both eyes were recorded by means of electro-oculography (EOG). The corresponding force development in muscles of the more affected eye in patients and the non-dominant eye in normals was measured, using a suction contact lens/strain gauge technique. RESULTS: Steady-state tension in the patients was increased in all directions of gaze both horizontally and vertically, most markedly for vertical fixations in the upper field of gaze. However, peak tension was increased only for the downward movements in the upper field of gaze and for the horizontal movements in the abduction field of gaze. Vertical saccadic velocity was slower than normal in downward movements, and horizontal saccadic velocity was reduced in the abduction field of gaze. CONCLUSION: The increased active eye muscle tension in different directions of gaze could represent an adaptational mechanism of the ocular motor system to overcome the eye movement restriction in TAO.

Significance of orbital fatty tissue for exophthalmos in thyroid-associated ophthalmopathy.

PURPOSE: To correlate exophthalmos with the volume of extraocular muscle and orbital fatty tissue in thyroid-associated ophthalmopathy (TAO), using MRI that enables the orbital soft tissues to be well defined. METHODS: Thirty-three orbits, 20 from 10 patients with TAO and 13 from 13 controls, were employed. T1-weighted orbital MR slices 2 or 3 mm thick were obtained in axial, coronal and sagittal planes. Tracing the outlines of each structure, we measured the total sectional areas. Volumes of the extraocular muscle, of the fatty tissue and of the bony orbital cavity were calculated by multiplying the slice thickness. Exophthalmos was also measured using axial MRI. RESULTS: In TAO the volume increment of orbital fatty tissue (6.19 cm(3)) was much greater than that of extraocular muscle (1.16 cm(3)). Increase of exophthalmos by 1 mm needed a total orbital volume increment of 0.92 cm(3). The total orbital fatty tissue volume (correlation coefficient 0.70, P=0.06%) and the anterior orbital fatty tissue volume (0.64, P=0.23%) were more closely correlated with the degree of exophthalmos than was extraocular muscle volume (0.58, P=0.8%). Moreover, the volume increment of extraocular muscle and orbital fatty tissue was not always proportional. CONCLUSION: The results show that the orbital fatty tissue involvement is closely related to the degree of exophthalmos. For studying exophthalmos in TAO, the volumetric change, not only in ocular muscles, but also in orbital fatty tissue, should be taken into consideration.