Sunny Y. Shen

Rationale and Methodology for a Population-Based Study of Eye Diseases in Malay People: The Singapore Malay Eye Study (SiMES)

Purpose: Although there are approximately 200 million people of Malay ethnicity living in Asia, the burden and risk factors of blinding eye diseases in this ethnic group are unknown. This study summarizes the rationale and study design of a population-based study of eye diseases among adult Malays in Singapore. Methods: A population-based cross-sectional study of Malays was designed in Singapore. The sampling frame consisted of all Malays aged 40–79 living in designated study areas in southwestern Singapore. From a list of 16,069 names provided by the Ministry of Home Affairs, age-stratified random sampling was used to select 5,600 names (1,400 people from each decade of 40–49, 50–59, 60–69, and 70–79 years). The target sample size for this study was 3,150 persons. Selected individuals were invited to a centralized clinic by letters, telephone calls, and home visits. Participants underwent standardized interview and assessment of blood pressure, anthropometry, presenting and best-corrected visual acuity, subjective refraction, ocular biometry, Goldmann tonometry, slit-lamp biomicroscopy, optic disc imaging, digital lens, and retinal photography. Blood and urine samples were collected for biochemical analyses and further stored for future studies. Selected participants also had gonioscopic examination, visual fields test, and assessment of ankle and brachial blood pressure to detect presence of peripheral vascular disease. Conclusions: This study provides population-based data on the prevalence of and risk factors for age-related eye diseases in people of Malay ethnicity in Singapore. Data from this study allow further understanding of the etiology and impact of eye diseases in this ethnic group.

The Prevalence and Types of Glaucoma in Malay People : The Singapore Malay Eye Study

PURPOSE To assess the prevalence and types of glaucoma in an Asian Malay population. METHODS The Singapore Malay Eye Study is a population-based, cross-sectional survey that examined 3280 (78.7% response) persons aged 40 to 80 years. Participants underwent a standardized clinical examination including slit-lamp biomicroscopy, Goldmann applanation tonometry, and dilated optic disc assessment. Participants who were suspected to have glaucoma also underwent visual field examination (24-2 SITA standard, Humphrey Visual Field Analyzer II), gonioscopy, and repeat applanation tonometry. Glaucoma was defined according to International Society for Geographical and Epidemiologic Ophthalmology criteria. RESULTS Of the 3280 participants, 150 (4.6%) had diagnosed glaucoma, giving an age- and sex-standardized prevalence of 3.4% (95% confidence interval [CI], 3.3%-3.5%). The age- and sex-standardized prevalence of primary open-angle glaucoma was 2.5% (95% CI, 2.4%-2.6%), primary angle-closure glaucoma 0.12% (95% CI, 0.10%-0.14%), and secondary glaucoma 0.61% (95% CI, 0.59%-0.63%). Of the 150 glaucoma cases, only 12 (8%) had a previous known history of glaucoma. Twenty-seven (18%) eyes had low vision (based on best corrected visual acuity logarithm of the minimal angle of resolution [logMAR] >0.30 to <1.00 in the eye with glaucoma for unilateral cases; and based on the better eye for bilateral cases) and 15 (10%) were blind (logMAR, >/=1.00). CONCLUSIONS The prevalence of glaucoma among Malay persons 40 years of age and older in Singapore is 3.4%, comparable to ethnic Chinese people in Singapore and other racial/ethnic groups in Asia. As in Chinese, Caucasians, and African people, primary open-angle glaucoma was the main form of glaucoma in this population. More than 90% of glaucoma cases were previously undetected.

Prevalence and Causes of Low Vision and Blindness in an Urban Malay Population: The Singapore Malay Eye Study

OBJECTIVE To describe the prevalence and causes of low vision and blindness in a Malay population. METHODS A population-based, cross-sectional study of 3280 participants of Malay ethnicity, aged 40 to 79 years, was conducted. Participants underwent standardized ophthalmic assessments to determine (1) presenting and best-corrected visual acuity according to US and modified World Health Organization definitions of blindness and low vision and (2) the primary causes of visual impairment. RESULTS Of 4168 eligible individuals, 3280 participated in the study (78.7%). The population-weighted prevalence of bilateral blindness was 0.3% and of bilateral low vision, 4.4% (US definition of presenting visual acuity). After best-corrected visual acuity, the population-weighted prevalence of bilateral blindness was reduced to 0.1% and bilateral low vision to 1.0%. Cataract was the main cause of presenting unilateral (38.9%) and bilateral (65.2%) blindness, whereas undercorrected refractive error was the main cause of presenting unilateral (68.8%) and bilateral (52.2%) low vision. Diabetic retinopathy, age-related macular degeneration, and glaucoma were the other leading causes of blindness and low vision. CONCLUSIONS The age-standardized prevalences of bilateral blindness and low vision in a Malay population were lower when compared with other Asian studies. Undercorrected refractive error and cataract are the leading causes of visual impairment among the Malay adult population in Singapore.

Determinants of the Optic Cup to Disc Ratio in an Asian Population: The Singapore Malay Eye Study (SiMES)

OBJECTIVE To describe the distribution and determinants of the optic cup to disc ratio (CDR) in Malay adults in Singapore. METHODS This population-based, age-stratified study examined 3280 Malay people aged 40 to 80 years in Singapore. Participants underwent a standardized interview and an ocular examination. A slitlamp examination measured the vertical dimensions of the disc and cup, excluding areas of peripapillary atrophy and the Elschnig scleral ring. RESULTS Vertical CDR was recorded for 3228 right eyes and 3237 left eyes. The mean (SD) CDR was 0.40 (0.15) in both eyes. The CDR in the right eye increased with age (P < .001) and was greater in men vs women (age-adjusted CDR, 0.42 vs 0.39; P < .001). In multiple linear regression, significant determinants of greater CDR were increasing age, male sex, higher intraocular pressure (IOP), lower diastolic blood pressure, lower body mass index, and previous cataract surgery. Of these, higher IOP was the most important determinant of the CDR. After excluding 149 persons with glaucoma, male sex, higher IOP, lower diastolic blood pressure, lower body mass index, and diabetes mellitus were significant predictors of greater CDR. CONCLUSION Greater vertical CDR was related to male sex, higher IOP, lower diastolic blood pressure, and lower body mass index.

Variation of Angle Parameters in Asians: An Anterior Segment Optical Coherence Tomography Study in a Population of Singapore Malays

PURPOSE To assess variations in angle parameters using anterior segment optical coherence tomography (AS-OCT) and to investigate demographic, ocular and systemic associations of angle width. METHODS This was a substudy of a population based, cross-sectional survey of 3280 (78.7% response rate) Malay people aged 40 to 80 years in Singapore. All participants underwent a standardized interview and ocular and systemic examination. AS-OCT was performed on 291 consecutive patients in standardized dark conditions. Angle opening distance (AOD-500) and trabecular-iris space area (TISA-500) 500 microm from the scleral spur were determined for the nasal and temporal angles. Anterior chamber depth (ACD) was also measured. RESULTS AS-OCT measurements were analyzed in 239 (82.1%) right eyes. Mean AOD 500 was smaller in women than in men, both nasally (0.255 vs. 0.293 mm, P = 0.026) and temporally (0.245 vs. 0.286 mm, P = 0.023). Mean TISA-500 was smaller in women in the nasal quadrant only (0.104 vs. 0.117 mm, P = 0.035). Mean ACD was smaller in women than in men (2.71 vs. 2.87 mm, P = 0.001). Multiple linear regression showed that axial length and ACD were significantly associated with AOD-500 and TISA-500 both nasally (adjusted R(2) = 0.34 for AOD-500 and 0.20 for TISA-500) and temporally (adjusted R(2) = 0.35 for AOD-500 and 0.24 for TISA-500). Body mass index, HbA(1c), systolic blood pressure, intraocular pressure, cup-to-disc ratio, and central corneal thickness were not significantly associated with AOD-500, TISA-500, or ACD. CONCLUSIONS In this Malay population, angle width measured by AS-OCT was smaller in women than in men, and in eyes with shorter axial length and shallower ACD.

Normative Measurements of the Chinese Extraocular Musculature by High-Field Magnetic Resonance Imaging

PURPOSE To establish the normal measurements of diameter and cross-sectional area of the Chinese extraocular muscles (EOMs) and optic nerve-sheath complex (ON) as seen on high-field (3-Tesla; 3T) magnetic resonance imaging (MRI). METHODS Coronal 3T MRI of the orbit (TR, 700 ms; TE, 15 ms; FOV, 160 mm; matrix, 256 x 256; slice thickness, 1 mm; and slice gap, 0) was performed on 80 normal Chinese volunteers. T1-weighted images were analyzed with computer-assisted segmentation. The diameter and the cross-sectional area of EOMs and the ON were measured from the image plane at the posterior aspect of the globe and at 7 mm behind the globe. The maximum diameter of EOM was measured from their respective reconstructed images. RESULTS The normal measurement (mean +/- SD) of diameter at the posterior aspect of the globe: medial rectus (MR), 3.6 +/- 0.4 mm; inferior rectus (IR), 3.7 +/- 0.8 mm; lateral rectus (LR), 2.3 +/- 0.5 mm; superior oblique (SO), 2.4 +/- 0.6 mm; and the ON, 5.4 +/- 0.7 mm. The normal measurement of diameter 7 mm behind the globe: MR, 3.2 +/- 0.6 mm; IR, 3.9 +/- 0.8 mm; LR, 4.0 +/- 0.8 mm; SO, 2.2 +/- 0.7 mm; and ON, 4.2 +/- 0.5 mm. The normal measurement of cross-sectional area at the posterior aspect of the globe: superior muscle group (SMG), 28.2 +/- 6.5 mm(2); MR, 25.5 +/- 3.2 mm(2); IR, 26.9 +/- 7.2 mm(2); LR, 17.3 +/- 3.9 mm(2); SO, 10.5 +/- 3.5 mm(2); and ON, 27.6 +/- 6.1 mm(2). The normal measurement of cross-sectional area 7 mm behind the globe: SMG, 24.1 +/- 6.6 mm(2); MR, 19.1 +/- 4.6 mm(2); IR, 29.5 +/- 6.6 mm(2); LR, 32.3 +/- 6.5 mm(2); SO, 9.7 +/- 3.9 mm(2); and ON, 17.1 +/- 2.9 mm(2). The normal measurement of maximum diameter: SMG, 4.8 +/- 1.1 mm; MR, 5.1 +/- 0.9 mm; IR, 5.4 +/- 1.0 mm; and LR, 4.5 +/- 0.9 mm. CONCLUSIONS The Chinese 3T MRI EOMs and ON normative data may be useful in determining pathologic enlargement of the EOMs and ON in various orbital conditions. (ClinicalTrials.gov number, NCT00348413.).

Prospective audit of ptosis surgery at the Singapore National Eye Centre: two-year results.

Purpose: To evaluate the demographics, presentation, and surgical outcomes of patients undergoing ptosis surgery in an Asian population in a prospective manner. Methods: A prospective ptosis audit was conducted over a 2-year period from January 2010 to December 2011 in a tertiary eye hospital in Singapore. All patients undergoing ptosis surgery by, or under the supervision of, an oculoplastic-trained consultant in the institution were included. Institutional Review Board approval was obtained for the study. Results: This study comprises 302 patients, of which 236 were acquired and 66 were congenital ptosis cases. Levator repair (77.2%) was the most commonly performed procedure, followed by levator resection (13.9%) and brow suspension (8.9%). Forty-seven (10.1%) eyes had readjustment within 2 weeks, the reasons for readjustment being eyelid height undercorrection (n = 35), eyelid height overcorrection (n = 9), and unsatisfactory eyelid contour (n = 4). Postoperatively, 93.8% of patients showed an increase in marginal reflex distance-1 (MRD1), 91.3% achieved symmetry or <1 mm of asymmetry in MRD1, 98.5% had good eyelid contour, and 74.3% had symmetric eyelid crease. On a scale of 1 to 10, 83.1% of patients gave a subjective grade of 7 or better. Conclusions: This study is the first prospective ptosis surgery audit in an Asian population and takes a leading step in assessing both subjective and objective surgical outcomes in a prospective manner. With the continuation of this audit in years to come, it will allow us to generate clinical outcomes in a robust manner and allow for more reliable benchmarking with major centers elsewhere.

Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

Aims To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. Methods This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed. Results Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3). Conclusions Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the ‘IgG4-RD’ pathogenesis.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.