Graves ophthalmopathy: the bony orbit in optic neuropathy, its apical angular capacity, and impact on prediction of risk.

BACKGROUND AND PURPOSE: Optic neuropathy (ON), a serious complication of Graves ophthalmopathy, is often subclinical and masked by symptoms of orbitopathy. We examined herein bony and soft-tissue CT features associated with ON, including an angular assessment of orbital apex capacity, and their usefulness in the risk prediction of ON. MATERIALS AND METHODS: The CT scans of 41 patients with Graves ophthalmopathy (17 men, 24 women; mean age, 49.1 years) clinically diagnosed with (19 patients, 32 orbits) or without ON were evaluated by 2 independent raters. Quantitative linear and angular measurements of the orbital structures and bony walls and categoric scores of apical crowding and intracranial fat prolapse were assessed on a clinical workstation. Inter- and intrarater variability of these features was determined. The CT features of the 2 patient groups were compared, and multivariate logistic regression analysis was performed to evaluate the predictive features of ON. RESULTS: Bony orbital angles (P < .005), length of the lateral orbital wall (P < .05), muscular diameters (P < .0005), muscular bulk of the medial rectus muscle relative to the bony orbit (P < .05), and apical crowding (P < .0005) were associated with clinical ON. Stepwise multivariate logistic regression analysis revealed the muscle diameter index and medial and lateral wall angles to be independent predictors. Combining these in a single multivariate equation yielded sensitivity, specificity, and positive and negative predictive values of 73%, 90%, 82%, and 85%, respectively. CONCLUSIONS: Orbital wall angles, especially the medial wall, and muscular enlargement are independent risk predictors.

Pseudoretinoblastoma in enucleated eyes of Asian patients.

INTRODUCTION: Retinoblastomas of the eye are a cause of childhood blindness and have a high rate of mortality, as well as a hereditary mode of transmission. Other conditions that mimic retinoblastomas are known as pseudoretinoblastomas, and are managed differently. Although pseudoretinoblastoma and the accuracy of retinoblastoma diagnosis have been reviewed in Caucasian patients, published studies in Asian patients are lacking. The purpose of this article is to report our experience with pseudoretinoblastomas in two major ophthalmological centres in Asia. METHODS: A case series of 28 enucleations carried out for suspected retinoblastoma at the Singapore National Eye Centre and KK Women's and Children's Hospital, Singapore, between January 1991 and December 2002, is reported. All cases were subjected to a detailed history from parents, followed by external ocular examination, slit-lamp biomicroscopy and binocular indirect ophthalmoscopy. Ancillary studies, such as B-scan ultrasonography and computed tomography, were employed as necessary to confirm the diagnosis. Histology was obtained on all cases. RESULTS: Of the 28 cases, 25 (89 percent) were found on histological analysis to be retinoblastomas. Three (11 percent) were pseudoretinoblastomas. There were two cases of Coat's disease and a case of presumed ocular toxocariasis. These three cases were described in detail. CONCLUSION: Although our sample size is small, the percentage of confirmed retinoblastomas was found to be only slightly higher than that found in western countries. Our findings are consistent with their findings that Coat's disease and presumed ocular toxocariasis are the more common causes of pseudoretinoblastoma.

Multifocal venous malformations: two interesting case presentations.

INTRODUCTION: Multiple venous abnormalities involving the orbit, head and neck regions have been previously described. We present two similar cases of low-flow orbital venous vascular malformations (VVMs) in association with multiple low-flow VVMs in the head and neck as well as in the peripheral limb. Literature search revealed that this association has not been previously reported. METHODS: Retrospective review of two patients with multifocal VVMs was performed. RESULTS: Case 1: A 46 year-old Chinese female had a history of multiple vascular lesions involving the right orbit, the tongue, right neck region, right arm and one finger. Valsalva manoeuvre resulted in distension of these lesions. CT scan of the orbits demonstrated bilateral low-flow VVMs. CT angiogram also revealed multiple developmental venous anomalies in the brain. Case 2: A 16 year-old Chinese female had a history of multiple venous malformations involving the neck, left forearm and oral region. Dynamic manoeuvres demonstrated the distensible nature of these lesions. MRI scans of the orbits showed bilateral extraconal low-flow VVMs. Similar mass lesions were seen on MRI scans of the neck. CONCLUSIONS: Multiple cervicofacial venous malformations with developmental abnormalities of the intracranial venous system have been described previously. However, their associations with similar VVMs in the peripheral limb regions have not been reported. Our cases illustrate this rare association. VVMs appear to be benign in nature with symptoms mainly due to mass effect. Management can be conservative in the absence of any sight threatening complication.

Factors associated with decompression and strabismus surgery in thyroid eye disease.

INTRODUCTION: Prognostication of the thyroid patient with eye disease aids in the choice of treatment strategy. To facilitate this, we investigated factors associated with decompression and/ or strabismus surgery in the Singaporean population. MATERIALS AND METHODS: A 5-year retrospective study was performed. Patients who required strabismus and/or decompression surgery (n = 23) were compared to those who did not undergo either surgery (n = 44). Individual and multivariate age-adjusted odds ratios were calculated to determine significant associations. RESULTS: Individually, male gender [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.5 to 13.4], uncontrolled hyperthyroidism (OR, 4.0; 95% CI, 1.1 to 14.3), steroid therapy (OR, 7.4; 95% CI, 2.3 to 24), diplopia (OR, 7.3; 95% CI, 2.3 to 23.1), objective vertical myopathy (OR, 11.7; 95% CI, 1.4 to 96.0), elevated intraocular pressure in the primary position (OR, 3.4; 95% CI, 1.2 to 10.0) and clinical evidence of optic neuropathy (OR, 13.1; 95% CI, 1.4 to 124.6) were significantly associated with the need for surgery. Logistic regression analysis showed the greater impact of male gender (OR, 4.2; 95% CI, 1.2 to 15.4), optic neuropathy (OR, 13.0; 95% CI, 1.2 to 143.7) and previous steroid therapy (OR, 4.2; 95%CI, 1.1 to 16.2) on prognostication. CONCLUSIONS: Chances of requiring strabismus and/or decompression surgery are significantly higher for male patients and those with uncontrolled hyperthyroidism. In particular, male patients with optic neuropathy and a history of previous steroid therapy warrant a graver prognosis.

Integrated hydroxyapatite implant and non-integrated implants in enucleated Asian patients.

INTRODUCTION: This study compares the outcome and complications of integrated hydroxyapatite implant and non-integrated orbital implants following enucleation in Asian patients. MATERIALS AND METHODS: This is a retrospective study of enucleated patients with coralline hydroxyapatite implants versus non-integrated implants (acrylic, glass and silicone) at the Singapore National Eye Centre from January 1991 to December 2000. The outcomes measured were implant migration, extrusion, socket infection, conjunctival dehiscence and implant exposure. Statistical analysis was done using the 2-sample t-test. RESULTS: Twenty-one patients had the hydroxyapatite implant and 38 non-integrated implants (27 acrylic, 9 glass and 2 silicone). The mean duration of follow-up was 2.7 years and 4 years for the hydroxyapatite implant and non-integrated implants respectively. Three patients with pre-existing severe socket contracture before enucleation surgeries were excluded from the study. Four cases of implant migration, 4 cases of implant extrusion and 3 cases of socket infection were encountered; all were sockets fitted with non-integrated implants. There was a higher rate of conjunctival dehiscence for sockets with hydroxyapatite implants (6 out of 21) compared to sockets with non-integrated implants (3 out of 35). This was statistically significant (P = 0.048). CONCLUSIONS: Implant complications of migration, extrusion and socket infection were found in non-integrated implants and none in coralline hydroxyapatite implants, which had a significantly higher rate of conjunctival dehiscence. Most of these were easily managed with only a small number progressing to implant exposure.

Thyroid autoantibody profiles in ophthalmic dominant and thyroid dominant Graves' disease differ and suggest ophthalmopathy is a multiantigenic disease.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) occurs in 25-50% of patients with Graves' disease (GD) and is occasionally seen in hypothyroid Hashimoto's disease or euthyroid individuals. The link between TAO and hyperthyroidism remains unclear. We hypothesized that qualitative or quantitative differences in thyroid antibodies might determine individual predisposition to these features. METHODS: In a prospective study over 3 years, thyroid antibody levels were measured in all patients diagnosed at the Singapore National Eye Centre to have GD. These patients had no known history of thyroid disease, presented with eye complaints and diagnosis was made by an ophthalmologist. A total of 31 patients were identified. Antibody levels were compared against 71 consecutive patients referred to a thyroid clinic (TC) for thyrotoxic symptoms in whom the diagnosis of GD was confirmed by a thyroidologist. FINDINGS: Thyroid autoantibody profiles of patients diagnosed at the ophthalmology centre (OC) and TC differed markedly. OC patients had significantly higher TSI (P = 0.003) but lower TPOAb (P = 0.008) and TgAb levels (P < 0.001). In contrast, TC patients had higher free T4 (P = 0.048) and higher TBII levels (P < 0.001). Antibody levels were correlated with four parameters of ophthalmopathy--chronic lid retraction, lid swelling, proptosis and extraocular myopathy (EOM). On univariate logistic regression analysis, TSI was a positive predictor and TPOAb and TgAb negative predictors of all four features. In the absence of TgAb, the odds ratios for individual TAO features ranged from 2.8 to 7.9, with corresponding values of 3.9-10.2 when TPOAb was absent. In stepwise logistic regression analysis, TSI was the strongest independent predictor of all aspects studied: lid fullness P = 0.001, proptosis P = 0.001, lid retraction P = 0.008, EOM P = 0.009. Among smokers, TPOAb were significantly lower (P = 0.044) but no association between smoking and the other antibodies was observed. INTERPRETATION: The study demonstrates markedly different thyroid autoantibody profiles in newly diagnosed GD patients with ophthalmic dominant as opposed to thyroid dominant features. It suggests differing antibody patterns are associated with predisposition to hyperthyroidism and orbitopathy. In addition, an association between smoking and low TPOAb levels was noted.

Congenital upper lid colobomas: management and visual outcome.

PURPOSE: Congenital upper lid colobomas may be associated with ocular and systemic anomalies. The ophthalmologist's role involves both the diagnosis and management of their various ocular structural defects and management of the visual development. METHODS: All cases of congenital eyelid colobomas referred to the Singapore National Eye Centre between July 1992 and July 1995 were assessed for the extent of the eyelid defect, associated ocular anomalies, status of the cornea, and any systemic anomalies. RESULTS: Four infants were tested during this period. The mean follow-up was 25 months (range, 16 to 30 months). All required surgical correction of their eyelid defects before 2 years of age. The patients also had refractive errors requiring amblyopia management. Three of the babies also needed other surgical procedures. CONCLUSIONS: Congenital upper eyelid colobomas are a potential threat to vision at an early age and a significant cosmetic blemish later in life. Early surgical intervention is usually required when the defect is larger than one third of the eyelid margin. Close monitoring of the visual development of patients with congenital upper eyelid colobomas is also essential since the risk of amblyopia in these patients is high.

Graves' ophthalmopathy in the absence of elevated free thyroxine and triiodothyronine levels: prevalence, natural history, and thyrotropin receptor antibody levels.

The aims of this study were to (a) determine the prevalence of patients without elevated thyroid hormone levels in Graves' ophthalmopathy (GO) using current generation free thyroid hormone assays, (b) measure the prevalence of thyrotropin receptor antibodies (TRAb) in these cases, and (c) identify possible predictors of hyperthyroidism. Over a 30-month period, 1020 cases of thyroid eye disease were evaluated, of which only 19 (1.9%) met the diagnostic criteria. Ten (1%) had subclinical thyrotoxicosis, 7 (0.7%) were euthyroid, and 2 (0.2%) were hypothyroid as determined by a third-generation thyrotropin (TSH) assay. TRAb levels were measured in 16 of these 19 patients. The prevalence of TRAb varied according to the assay used. Polyethylene glycol-extracted thyroid-stimulating immunoglobulin (PEG-TSI), unfractionated thyroid-stimulating immunoglobulin (uTSI), first-generation porcine TSH-binding inhibitory immunoglobulin (pTBII), and second-generation human TSH-binding inhibitory immunoglobulin (hTBII) assays were positive in 93.8%, 50%, 18.8%, and 81.3% of patients, respectively. TRAb was detected by at least one method in all patients. Patients were followed up for 15 to 45 months. Hyperthyroidism developed in 4 patients (25%). Suppressed TSH levels and elevated TBII were predictors of hyperthyroidism. When sensitive assays are used, the prevalence of GO patients without elevated thyroid hormone levels is extremely low. The sensitivities of assays for TRAb detection differ substantially in these cases. PEG extraction improves the detection rate of TSI (p = 0.02), and hTBII assays improve the detection of TBII in these patients (p = 0.002). The high prevalence of TRAb in such cases supports a role for these antibodies in the pathogenesis of thyroid-associated eye disease.

The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy.

Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.

Acute orbital cellulitis--a review of 17 cases.

This is a retrospective study of 17 patients who were admitted for orbital cellulitis between August 1989 and February 1994. The epidemiology, possible source of infection, the causative organisms and effectiveness of treatment were reviewed. The results showed that one-third of the cases occurred in the first decade of life. Paranasal sinusitis was the main source of infection in 11 (65%) patients. Thirteen patients (76.5%) developed orbital and periocular abscesses requiring surgical drainage. Two out of 17 eyes lost vision despite intensive treatment. Orbital cellulitis is a blinding ocular emergency associated with high morbidity. Immediate treatment is necessary to avoid devastating complications such as optic nerve compression, panophthalmitis or intracranial spread of infections. Cases with abscess formation required early surgical drainage. Combined orbito-otorhinolaryngologic approach is recommended for drainage of orbital abscess with associated paranasal sinus infection.

Results of dacryocystorhinostomy in Singapore General Hospital.

A total of fifty dacryocystorhinostomies (DCRs) done between 1983 and 1988 were reviewed. A success rate of 86% was found in 47 patients who had obstruction of the lacrimal sac and/or duct. Our results, surgical technique and reasons for failure will be discussed.