Downloaded from http://bjo.bmj.com/ on November 5, 2014 - Published by group.bmj.com
BJO Online First, published on October 31, 2014 as 10.1136/bjophthalmol-2014-305649 Clinical science
Thyroid eye disease: a Southeast Asian experience Nigel C S Lim,1 Gangadhara Sundar,2 Shantha Amrith,2 Kok Onn Lee3 1
Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 2 Orbit & Oculofacial Surgery, Department of Ophthalmology, National University Health System, Singapore 3 Division of Endocrinology, Department of Medicine, National University of Singapore Correspondence to Dr Gangadhara Sundar, Head & Senior Consultant, Orbit & Oculofacial Surgery, Department of Ophthalmology, National University Hospital, 1E, Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228, Singapore; [email protected] Received 28 June 2014 Revised 2 September 2014 Accepted 30 September 2014
ABSTRACT Aim To study the demographics, comorbidities, clinical manifestations and treatment methods of thyroid eye disease (TED) in Singapore. Methods In this retrospective case series, we analysed the case records of all patients with TED who presented at our multidisciplinary Thyroid Eye Clinic from November 2002 to October 2012. Results There were a total of 174 patients—111 female patients (63.8%) and 63 male patients (36.2%). The majority of the patients were ethnically Chinese (80.5%), followed by Malay (10.3%) and Indian (6.3%). The mean age was 40.2 years (SD±15.5, range 0.3–87.0). The commonest sign on ophthalmic examination was eyelid retraction (62.1%), followed by proptosis (61.0%) and lid lag (57.5). Acquired epiblepharon and corneal erosions were noted in 11.5% and 29.3% respectively. Eight patients (4.6%) had dysthyroid optic neuropathy. The mean exophthalmometry reading was 18.8 mm (SD±3.32, range 10.0–28.0). Mild, moderate and severe disease was noted in 71.3%, 20.7% and 8.0% respectively. Thyroid dysfunction was managed with anti-thyroid medication only (40.2%), β blockers (19.5%), thyroxine replacement (14.4%), radioactive iodine (14.4%) and block-replace regime (9.8%). Clinically significant active orbitopathy was managed with intravenous corticosteroids (12.1%). Surgical procedures consisted of thyroidectomy (10.3%), eyelid surgery (8.6%), orbital decompression (7.5%), epiblepharon correction (2.3%) and strabismus surgery (0.6%). Conclusions Corneal erosion secondary to acquired epiblepharon is a common sign in East Asian patients with TED, thus increased awareness among physicians should be encouraged. Mean exophthalmometry values and frequencies of upper eyelid retraction and oedema are lower in East Asian patients compared with Caucasian patients. Among Singapore’s multi-ethnic population, Malay patients with TED had the highest exophthalmometry reading.
INTRODUCTION
To cite: Lim NCS, Sundar G, Amrith S, et al. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-305649
Thyroid eye disease (TED) is an autoimmune inflammatory disorder which commonly occurs in patients with autoimmune hyperthyroidism (Graves’ disease), and rarely in patients with Hashimoto’s thyroiditis or in patients who are euthyroid. Commonly bilateral, the signs of TED include upper and/or lower eyelid retraction, proptosis, chemosis and restrictive myopathy. It can potentially result in sight-threatening complications such as optic neuropathy or corneal ulceration. Another severe disabling feature is diplopia, either in primary gaze or within 30° from primary gaze. Even when the vision is unaffected, the disease may have physical, aesthetic, functional and
psychosocial consequences on affected individuals and their families. To our knowledge, there is a paucity of literature on TED in Singapore and Southeast Asia. Previous local studies have only specifically investigated autoantibody profiles1 and radiological signs2 in TED. Furthermore, there are very few studies on the ethnic differences of TED, which may have important clinical implications on diagnosis and management of the disease. This retrospective study aims to analyse the demographics, comorbidities, clinical manifestations and treatment methods of patients with TED seen over a 10-year period in a multidisciplinary Thyroid Eye Clinic at a tertiary care referral centre to further understand the clinico-epidemiological features of the disease in Southeast Asians.
MATERIALS AND METHODS In this retrospective case series, we identified all patients who were diagnosed with TED at the National University Hospital Singapore between November 2002 and October 2012. The diagnosis of TED was based on the Bartley and Gorman criteria—TED is considered to be present if eyelid retraction occurs in association with laboratory evidence of thyroid dysfunction, exophthalmos, optic nerve dysfunction or extraocular muscle involvement. If eyelid retraction is absent, then TED may be diagnosed only if exophthalmos, optic nerve involvement or restrictive myopathy is associated with thyroid dysfunction.3 All patients had been evaluated using the International Thyroid Eye Disease Society (ITEDS) VISA first visit and follow-up forms.4 Demographics, predisposing factors, clinical characteristics and treatment methods were retrospectively reviewed from medical records. Features of ophthalmic examination that were reviewed included best corrected visual acuity, ocular ductions, presence of strabismus, lagophthalmos, upper and lower eyelid retraction, lid lag and keratopathy. Symptoms of diplopia were recorded based on the modified Bahn–Gorman grading5—grade 0 (no diplopia), grade 1 (diplopia with horizontal or vertical gaze), grade 2 (intermittent diplopia in straight gaze) or grade 3 (constant diplopia in straight gaze). Upper eyelid retraction was noted when the upper eyelid was at or above the superior corneoscleral limbus in primary position without frontalis muscle contraction, while lower eyelid retraction was noted when the lower eyelid was below the inferior corneoscleral limbus in primary position.3 The degree of proptosis was measured using Hertel exophthalmometer. Objective measures of optic neuropathy reviewed included loss of central visual acuity, visual field defect, acquired dyschromatopsia on Ishihara colour test, relative
Lim NCS, et al. Br J Ophthalmol 2014;0:1–7. doi:10.1136/bjophthalmol-2014-305649
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on November 5, 2014 - Published by group.bmj.com
Clinical science
From November 2002 to October 2012, a total of 174 patients were diagnosed with TED at the National University Hospital,
Singapore (NUH). The majority (80.5%) of patients were referred from the Endocrine Department at NUH. Mean follow-up duration was 2.38 years (range 0–14.1). There were 38 smokers (21.8%), and significantly more male smokers (68.4%) than female smokers (31.6%) ( p4/10 was classified as clinically significant active disease (figure 1), while a CAS score of 60 Mean Ethnicity Chinese Malay Indian Others Comorbidities Hypertension Diabetes mellitus Pretibial myxedema Thyroid acropachy Rheumatoid arthritis Myasthenia gravis Vitiligo Psoriasis Presenting complaint Lid stare Prominent eyes Lid swelling Ocular irritation Diplopia Grade 1 (horizontal/vertical gaze) Grade 2 (intermittent, straight gaze) Grade 3 (constant straight gaze) Retrobulbar ache Epiphora Light sensitivity Blurring of vision Colour desaturation Head tilt Diurnal variation Clinical features Lid retraction Upper eyelid retraction only Lower eyelid retraction only Upper and lower eyelid retraction Proptosis Mean exophthalmometry Lid lag Conjunctival injection Lid oedema Limited ocular motility Lagophthalmos Punctate epithelial erosions Chemosis Acquired epiblepharon Upper eyelid only Lower eyelid only Upper and lower eyelid
Number of patients (%)
63 (36.2) 111 (63.8) 13 (7.5) 69 (39.7) 77 (44.3) 15 (8.6) 40.2 years (SD±15.5, range 0.3–87.0) 140 (80.5) 18 (10.3) 11 (6.3) 5 (2.9) 38 (21.8) 8 (4.6) 4 (2.3) 3 (1.7) 3 (1.7) 2 (1.1) 1 (0.6) 1 (0.6) 142 (81.6) 132 (75.9) 63 (36.2) 51 (29.3) 46 (26.4) 34 (19.5) 4 (2.3) 8 (4.6) 44 (25.3) 33 (19.1) 13 (7.5) 11 (6.3) 5 (2.9) 4 (2.3) 4 (2.3) 108 (62.1) 71 (40.8) 77 (44.3) 40 (23.0) 106 (61.0) 18.8 mm (SD±3.32, range 10.0–28.0) 100 (57.5) 97 (55.7) 78 (44.8) 68 (39.1) 57 (32.8) 51 (29.3) 49 (28.2) 20 (11.5) 6 (3.4) 17 (9.8) 3 (1.7) Continued
Lim NCS, et al. Br J Ophthalmol 2014;0:1–7. doi:10.1136/bjophthalmol-2014-305649
Table 1
Continued
Characteristics Lid redness Caruncular oedema Optic neuropathy RAPD Dyschromatopsia SLK Optic disc oedema Mean VISA score Disease Activity Active (VISA >4/10) Inactive (VISA 4/10, was present in 19 patients, while 155 patients had inactive disease (VISA ≤4/10). The majority of patients had mild 3
Downloaded from http://bjo.bmj.com/ on November 5, 2014 - Published by group.bmj.com
Clinical science Table 2 patients
Hertel exophthalmometry values in different groups of
Parameters Smoking status Smokers Non-smokers Gender Male Female Race Chinese Malay Indian Others Age group Paediatric (≤18 years) Adults (>18 years) Epiblepharon Absent Present Optic neuropathy Absent Present Disease activity Inactive Active Disease severity Mild Moderate Severe
Mean exophthalmometry values (mm)
p Value 0.0534
19.8±3.70 (range 13.0–28.0) 18.5±3.15 (range 10.0–26.5) 0.126 19.3±3.29 (range 12.0–27.0) 18.5±3.31 (range 10.0–28.0) 0.001 18.8±3.33 19.4±2.96 17.7±3.50 18.2±4.04
(range (range (range (range
12.0–28.0) 10.0–23.0) 10.0–23.0) 14.0–23.0) 0.0489
17.2±2.29 (range 13.0–21.0) 18.8±3.24 (range 10.0–28.0) 0.218 18.9±3.40 (range 10.0–28.0) 17.9±2.56 (range 14.0–23.0) 0.402 18.8±3.39 (range 10.0–28.0) 18.4±1.08 (range 17.5–21.0) 0.0450 18.6±3.32 (range 10.0–28.0) 20.3±3.00 (range 13.0–26.0) 0.007 18.3±3.12 (range 10.0–28.0) 20.1±3.55 (range 14.0–27.0) 19.8±3.47 (range 14.0–23.5)
Numbers in bold represent statistically significant values (p 4/10 or CAS score of ≥3/7 are defined as having ‘clinically significant’ active disease. These patients require more aggressive therapy such as IVMP as first-line treatment. Patients with moderate or severe disease require a higher dose of IVMP (1 g/day) for 3 days, for a total of three to six cycles in an outpatient setting. Steroid-sparing agents such as azathioprine, methotrexate or cyclosporine may be considered if moderate or no improvement has occurred. Rituximab is an alternative biological drug, which may be used in patients who are refractive to the above therapy. For patients with absolute contraindications to IVMP or steroid-sparing agents, orbital radiotherapy or decompression may be considered. Diabetic retinopathy, severe hypertension and age
BJO Online First, published on October 31, 2014 as 10.1136/bjophthalmol-2014-305649 Clinical science
Thyroid eye disease: a Southeast Asian experience Nigel C S Lim,1 Gangadhara Sundar,2 Shantha Amrith,2 Kok Onn Lee3 1
Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 2 Orbit & Oculofacial Surgery, Department of Ophthalmology, National University Health System, Singapore 3 Division of Endocrinology, Department of Medicine, National University of Singapore Correspondence to Dr Gangadhara Sundar, Head & Senior Consultant, Orbit & Oculofacial Surgery, Department of Ophthalmology, National University Hospital, 1E, Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228, Singapore; [email protected] Received 28 June 2014 Revised 2 September 2014 Accepted 30 September 2014
ABSTRACT Aim To study the demographics, comorbidities, clinical manifestations and treatment methods of thyroid eye disease (TED) in Singapore. Methods In this retrospective case series, we analysed the case records of all patients with TED who presented at our multidisciplinary Thyroid Eye Clinic from November 2002 to October 2012. Results There were a total of 174 patients—111 female patients (63.8%) and 63 male patients (36.2%). The majority of the patients were ethnically Chinese (80.5%), followed by Malay (10.3%) and Indian (6.3%). The mean age was 40.2 years (SD±15.5, range 0.3–87.0). The commonest sign on ophthalmic examination was eyelid retraction (62.1%), followed by proptosis (61.0%) and lid lag (57.5). Acquired epiblepharon and corneal erosions were noted in 11.5% and 29.3% respectively. Eight patients (4.6%) had dysthyroid optic neuropathy. The mean exophthalmometry reading was 18.8 mm (SD±3.32, range 10.0–28.0). Mild, moderate and severe disease was noted in 71.3%, 20.7% and 8.0% respectively. Thyroid dysfunction was managed with anti-thyroid medication only (40.2%), β blockers (19.5%), thyroxine replacement (14.4%), radioactive iodine (14.4%) and block-replace regime (9.8%). Clinically significant active orbitopathy was managed with intravenous corticosteroids (12.1%). Surgical procedures consisted of thyroidectomy (10.3%), eyelid surgery (8.6%), orbital decompression (7.5%), epiblepharon correction (2.3%) and strabismus surgery (0.6%). Conclusions Corneal erosion secondary to acquired epiblepharon is a common sign in East Asian patients with TED, thus increased awareness among physicians should be encouraged. Mean exophthalmometry values and frequencies of upper eyelid retraction and oedema are lower in East Asian patients compared with Caucasian patients. Among Singapore’s multi-ethnic population, Malay patients with TED had the highest exophthalmometry reading.
INTRODUCTION
To cite: Lim NCS, Sundar G, Amrith S, et al. Br J Ophthalmol Published Online First: [ please include Day Month Year] doi:10.1136/bjophthalmol2014-305649
Thyroid eye disease (TED) is an autoimmune inflammatory disorder which commonly occurs in patients with autoimmune hyperthyroidism (Graves’ disease), and rarely in patients with Hashimoto’s thyroiditis or in patients who are euthyroid. Commonly bilateral, the signs of TED include upper and/or lower eyelid retraction, proptosis, chemosis and restrictive myopathy. It can potentially result in sight-threatening complications such as optic neuropathy or corneal ulceration. Another severe disabling feature is diplopia, either in primary gaze or within 30° from primary gaze. Even when the vision is unaffected, the disease may have physical, aesthetic, functional and
psychosocial consequences on affected individuals and their families. To our knowledge, there is a paucity of literature on TED in Singapore and Southeast Asia. Previous local studies have only specifically investigated autoantibody profiles1 and radiological signs2 in TED. Furthermore, there are very few studies on the ethnic differences of TED, which may have important clinical implications on diagnosis and management of the disease. This retrospective study aims to analyse the demographics, comorbidities, clinical manifestations and treatment methods of patients with TED seen over a 10-year period in a multidisciplinary Thyroid Eye Clinic at a tertiary care referral centre to further understand the clinico-epidemiological features of the disease in Southeast Asians.
MATERIALS AND METHODS In this retrospective case series, we identified all patients who were diagnosed with TED at the National University Hospital Singapore between November 2002 and October 2012. The diagnosis of TED was based on the Bartley and Gorman criteria—TED is considered to be present if eyelid retraction occurs in association with laboratory evidence of thyroid dysfunction, exophthalmos, optic nerve dysfunction or extraocular muscle involvement. If eyelid retraction is absent, then TED may be diagnosed only if exophthalmos, optic nerve involvement or restrictive myopathy is associated with thyroid dysfunction.3 All patients had been evaluated using the International Thyroid Eye Disease Society (ITEDS) VISA first visit and follow-up forms.4 Demographics, predisposing factors, clinical characteristics and treatment methods were retrospectively reviewed from medical records. Features of ophthalmic examination that were reviewed included best corrected visual acuity, ocular ductions, presence of strabismus, lagophthalmos, upper and lower eyelid retraction, lid lag and keratopathy. Symptoms of diplopia were recorded based on the modified Bahn–Gorman grading5—grade 0 (no diplopia), grade 1 (diplopia with horizontal or vertical gaze), grade 2 (intermittent diplopia in straight gaze) or grade 3 (constant diplopia in straight gaze). Upper eyelid retraction was noted when the upper eyelid was at or above the superior corneoscleral limbus in primary position without frontalis muscle contraction, while lower eyelid retraction was noted when the lower eyelid was below the inferior corneoscleral limbus in primary position.3 The degree of proptosis was measured using Hertel exophthalmometer. Objective measures of optic neuropathy reviewed included loss of central visual acuity, visual field defect, acquired dyschromatopsia on Ishihara colour test, relative
Lim NCS, et al. Br J Ophthalmol 2014;0:1–7. doi:10.1136/bjophthalmol-2014-305649
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://bjo.bmj.com/ on November 5, 2014 - Published by group.bmj.com
Clinical science
From November 2002 to October 2012, a total of 174 patients were diagnosed with TED at the National University Hospital,
Singapore (NUH). The majority (80.5%) of patients were referred from the Endocrine Department at NUH. Mean follow-up duration was 2.38 years (range 0–14.1). There were 38 smokers (21.8%), and significantly more male smokers (68.4%) than female smokers (31.6%) ( p4/10 was classified as clinically significant active disease (figure 1), while a CAS score of 60 Mean Ethnicity Chinese Malay Indian Others Comorbidities Hypertension Diabetes mellitus Pretibial myxedema Thyroid acropachy Rheumatoid arthritis Myasthenia gravis Vitiligo Psoriasis Presenting complaint Lid stare Prominent eyes Lid swelling Ocular irritation Diplopia Grade 1 (horizontal/vertical gaze) Grade 2 (intermittent, straight gaze) Grade 3 (constant straight gaze) Retrobulbar ache Epiphora Light sensitivity Blurring of vision Colour desaturation Head tilt Diurnal variation Clinical features Lid retraction Upper eyelid retraction only Lower eyelid retraction only Upper and lower eyelid retraction Proptosis Mean exophthalmometry Lid lag Conjunctival injection Lid oedema Limited ocular motility Lagophthalmos Punctate epithelial erosions Chemosis Acquired epiblepharon Upper eyelid only Lower eyelid only Upper and lower eyelid
Number of patients (%)
63 (36.2) 111 (63.8) 13 (7.5) 69 (39.7) 77 (44.3) 15 (8.6) 40.2 years (SD±15.5, range 0.3–87.0) 140 (80.5) 18 (10.3) 11 (6.3) 5 (2.9) 38 (21.8) 8 (4.6) 4 (2.3) 3 (1.7) 3 (1.7) 2 (1.1) 1 (0.6) 1 (0.6) 142 (81.6) 132 (75.9) 63 (36.2) 51 (29.3) 46 (26.4) 34 (19.5) 4 (2.3) 8 (4.6) 44 (25.3) 33 (19.1) 13 (7.5) 11 (6.3) 5 (2.9) 4 (2.3) 4 (2.3) 108 (62.1) 71 (40.8) 77 (44.3) 40 (23.0) 106 (61.0) 18.8 mm (SD±3.32, range 10.0–28.0) 100 (57.5) 97 (55.7) 78 (44.8) 68 (39.1) 57 (32.8) 51 (29.3) 49 (28.2) 20 (11.5) 6 (3.4) 17 (9.8) 3 (1.7) Continued
Lim NCS, et al. Br J Ophthalmol 2014;0:1–7. doi:10.1136/bjophthalmol-2014-305649
Table 1
Continued
Characteristics Lid redness Caruncular oedema Optic neuropathy RAPD Dyschromatopsia SLK Optic disc oedema Mean VISA score Disease Activity Active (VISA >4/10) Inactive (VISA 4/10, was present in 19 patients, while 155 patients had inactive disease (VISA ≤4/10). The majority of patients had mild 3
Downloaded from http://bjo.bmj.com/ on November 5, 2014 - Published by group.bmj.com
Clinical science Table 2 patients
Hertel exophthalmometry values in different groups of
Parameters Smoking status Smokers Non-smokers Gender Male Female Race Chinese Malay Indian Others Age group Paediatric (≤18 years) Adults (>18 years) Epiblepharon Absent Present Optic neuropathy Absent Present Disease activity Inactive Active Disease severity Mild Moderate Severe
Mean exophthalmometry values (mm)
p Value 0.0534
19.8±3.70 (range 13.0–28.0) 18.5±3.15 (range 10.0–26.5) 0.126 19.3±3.29 (range 12.0–27.0) 18.5±3.31 (range 10.0–28.0) 0.001 18.8±3.33 19.4±2.96 17.7±3.50 18.2±4.04
(range (range (range (range
12.0–28.0) 10.0–23.0) 10.0–23.0) 14.0–23.0) 0.0489
17.2±2.29 (range 13.0–21.0) 18.8±3.24 (range 10.0–28.0) 0.218 18.9±3.40 (range 10.0–28.0) 17.9±2.56 (range 14.0–23.0) 0.402 18.8±3.39 (range 10.0–28.0) 18.4±1.08 (range 17.5–21.0) 0.0450 18.6±3.32 (range 10.0–28.0) 20.3±3.00 (range 13.0–26.0) 0.007 18.3±3.12 (range 10.0–28.0) 20.1±3.55 (range 14.0–27.0) 19.8±3.47 (range 14.0–23.5)
Numbers in bold represent statistically significant values (p 4/10 or CAS score of ≥3/7 are defined as having ‘clinically significant’ active disease. These patients require more aggressive therapy such as IVMP as first-line treatment. Patients with moderate or severe disease require a higher dose of IVMP (1 g/day) for 3 days, for a total of three to six cycles in an outpatient setting. Steroid-sparing agents such as azathioprine, methotrexate or cyclosporine may be considered if moderate or no improvement has occurred. Rituximab is an alternative biological drug, which may be used in patients who are refractive to the above therapy. For patients with absolute contraindications to IVMP or steroid-sparing agents, orbital radiotherapy or decompression may be considered. Diabetic retinopathy, severe hypertension and age
