Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper.

BACKGROUND: More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway. METHODS: In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. RESULTS: A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%). CONCLUSIONS: Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.).

IMPROVED SPECIFICITY OF POLYPOIDAL CHOROIDAL VASCULOPATHY DIAGNOSIS USING A MODIFIED EVEREST CRITERIA.

PURPOSE: To evaluate the performance of polypoidal choroidal vasculopathy (PCV) diagnosis using fundus camera-based indocyanine green angiography, comparing a single sign of "subretinal focal hyperfluorescence" on indocyanine green angiography with a modification of the EVEREST criteria. METHODS: Color fundus photograph, flash fundus camera-based fluorescein angiography, and indocyanine green angiography of 241 eyes of 230 consecutive patients with exudative maculopathy due to PCV or typical age-related macular degeneration were graded independently by 2 retinal specialists using a modified EVEREST criteria, which requires the presence of subretinal focal hyperfluorescence plus any 1 of 5 additional criteria. Discordant cases were adjudicated by a senior retinal specialist to arrive at the final diagnosis. Sensitivity, specificity, and area under the receiver operating curve of subretinal focal hyperfluorescence versus the EVEREST criteria and combinations of individual EVEREST criteria were compared. RESULTS: Among the 241 eyes with exudative maculopathy, 131 eyes had PCV and 110 eyes had typical age-related macular degeneration. Using a single sign of subretinal focal hyperfluorescence alone for the diagnosis of PCV, sensitivity was 85.3% and specificity was 80.9%, with an area under the receiver operating curve of 83.1%. When applying the EVEREST definition, sensitivity was reduced to 78.4% but specificity improved to 87.1% with a similar area under the receiver operating curve of 82.8%. The frequency of individual criteria was highly variable, with stereo nodular appearance (73.7%) and orange nodule (55.0%) being the most common and branching vascular network, massive hemorrhage, and hypofluorescent halo in the presence of subretinal focal hyperfluorescence being less common (21.5%-28.1%). CONCLUSION: The EVEREST criteria have a higher specificity for the diagnosis of PCV than subretinal focal hyperfluorescence alone and may be applied to flash fundus camera-based indocyanine green angiography in a clinical setting. Stereo nodular appearance is the most important additional criterion.

Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2).

PURPOSE: Our previous study, Atropine for the Treatment of Myopia 1 (ATOM1), showed that atropine 1% eyedrops were effective in controlling myopic progression but with visual side effects resulting from cycloplegia and mydriasis. The aim of this study was to compare efficacy and visual side effects of 3 lower doses of atropine: 0.5%, 0.1%, and 0.01%. DESIGN: Single-center, double-masked, randomized study. PARTICIPANTS: A total of 400 children aged 6-12 years with myopia of at least -2.0 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: Children were randomly assigned in a 2:2:1 ratio to 0.5%, 0.1%, and 0.01% atropine to be administered once nightly to both eyes for 2 years. Cycloplegic refraction, axial length, accommodation amplitude, pupil diameter, and visual acuity were noted at baseline, 2 weeks, and then every 4 months for 2 years. MAIN OUTCOME MEASURES: Myopia progression at 2 years. Changes were noted and differences between groups were compared using the Huber-White robust standard error to allow for data clustering of 2 eyes per person. RESULTS: The mean myopia progression at 2 years was -0.30±0.60, -0.38±0.60, and -0.49±0.63 D in the atropine 0.5%, 0.1%, and 0.01% groups, respectively (P=0.02 between the 0.01% and 0.5% groups; between other concentrations P > 0.05). In comparison, myopia progression in ATOM1 was -1.20±0.69 D in the placebo group and -0.28±0.92 D in the atropine 1% group. The mean increase in axial length was 0.27±0.25, 0.28±0.28, and 0.41±0.32 mm in the 0.5%, 0.1%, and 0.01% groups, respectively (P < 0.01 between the 0.01% and 0.1% groups and between the 0.01% and 0.5% groups). However, differences in myopia progression (0.19 D) and axial length change (0.14 mm) between groups were small and clinically insignificant. Atropine 0.01% had a negligible effect on accommodation and pupil size, and no effect on near visual acuity. Allergic conjunctivitis and dermatitis were the most common adverse effect noted, with 16 cases in the 0.1% and 0.5% atropine groups, and no cases in the 0.01% group. CONCLUSIONS: Atropine 0.01% has minimal side effects compared with atropine at 0.1% and 0.5%, and retains comparable efficacy in controlling myopia progression.

Prevalence of and racial differences in pterygium: a multiethnic population study in Asians.

PURPOSE: To describe the prevalence and risk factors of pterygium in a multiethnic Asian population and to examine racial differences. DESIGN: Population-based study in Singapore, located 1° north of the equator. PARTICIPANTS: Data were analyzed from 8906 participants from 3 population-based studies of Malays, Indians, and Chinese persons 40 years of age and older conducted between 2004 and 2011. METHODS: Standardized slit-lamp examinations were performed by trained study ophthalmologists to examine the anterior segment for evidence of pterygium. Every subject underwent standardized systemic and ocular examinations, interviewer-administered questionnaires, and blood investigations for risk factor assessment. Regression and principle component analysis models were constructed to study the relationship of race and other factors to pterygium. MAIN OUTCOME MEASURES: Any pterygium and severe (grade 3 or opaque) pterygium. RESULTS: The overall prevalence of any pterygium was 10.1% (n = 900), of which severe pterygium was seen in 1.6% (n = 142). The prevalence of any pterygium was more common in Malays (15.5%) than Chinese (7.0%; P<0.001) or Indians (7.0%; P<0.001). Multivariate analysis revealed increasing age (P<0.001), male gender (P<0.001), Malay race (P<0.001), and having a poorer education level (P<0.001) as significant factors for any pterygium. Race contributed significantly to presence of any pterygium (41%; P<0.001) or presence in both eyes (33%; P<0.001) compared with other risk factors. Severe pterygium was associated with outdoor occupation (P = 0.02), but race was not a significant risk factor in multivariate analysis. CONCLUSIONS: This population-based study in Asian persons of different races living in the same geographical location at the equator indicated that race is a significant risk factor for pterygium, with Malays having higher prevalence than Indians and Chinese, while controlling for other risk factors.

Retinal venular calibre dilatation after intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

BACKGROUND: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. DESIGN: Prospective interventional case series. PARTICIPANTS: Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. METHODS: Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. MAIN OUTCOME MEASURE: Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. RESULTS: Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). CONCLUSION: Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.

Singapore Malay Eye Study: rationale and methodology of 6-year follow-up study (SiMES-2).

BACKGROUND: To describe the rationale and study design of a follow-up epidemiological eye study among Singaporean Malay adults. DESIGN: Follow-up prospective population-based study. PARTICIPANTS: Participants of the Singapore Malay Eye Study (SiMES-1), which was conducted from August 2004 to June 2006. METHODS: This is a follow-up study of the 3280 participants who participated in the SiMES-1 and are residing in Singapore. All participants of this follow-up study will undergo various standardized validated questionnaires on socio-demographics, quality of life and impact of visual impairment. Participants will undergo assessment of blood pressure, anthropometry, presenting and best corrected visual acuity, subjective refraction, ocular biometry, slit lamp and dilated eye examination, Goldmann tonometry, optic disc imaging, digital lens and retinal photography. Retinal tomography, retinal optical coherence topography and fundus autofluorescence will also be performed. Gonioscopy and visual fields examination will be performed on selected individuals. MAIN OUTCOME MEASURES: Incidence, risk factors and impact of visual impairment and major eye diseases. RESULTS: A total of 3280 people who participated in the SiMES-1 will be contacted and invited to participate in this follow-up study. It is estimated that 12.8% of the participants will be deceased and there will be an 80% participation rate for the survivors of SiMES-1 (approximately 2288 participants). CONCLUSION: SiMES-2 will be one of the few follow-up epidemiological eye studies among Asians and will determine the cumulative 6-year incidence, progression, risk factors and impact of major eye diseases in Singaporean Malay adults.

Quantitative evaluation of anterior chamber parameters using anterior segment optical coherence tomography in primary angle closure mechanisms.

BACKGROUND: To evaluate different mechanisms of primary angle closure and to quantify anterior chamber parameters in these mechanisms using anterior segment optical coherence tomography in an Asian population. DESIGN: Hospital-based cross-sectional observational study. PARTICIPANTS: Forty-eight consecutive patients with primary angle closure glaucoma. METHODS: Patients underwent complete ophthalmic examination and imaging of nasal-temporal angles with anterior segment optical coherence tomography. Images were categorized into four primary angle closure mechanisms: pupil block, plateau iris configuration, Thick peripheral iris roll and exaggerated lens vault. Parameters computed: anterior chamber depth central, anterior chamber depth at 1000 µm and 2000 µm anterior to scleral spur, lens vault, anterior chamber area, angle opening distance, trabecular iris space area and iris thickness. MAIN OUTCOME MEASURE: Anterior chamber parameters and primary angle closure mechanisms. RESULTS: Mean values of anterior chamber depths: central (P < 0.001), at 2000 µm (P < 0.001), 1000 µm (P < 0.001), lens vault (P < 0.001), anterior chamber area (P < 0.001), were significantly different among the four groups. Multivariate analysis showed anterior chamber depths: central, and anterior chamber depth at 2000 µm and anterior chamber area were higher in plateau iris and Thick peripheral iris roll and lower in exaggerated lens vault (P < 0.001) as compared to pupil block mechanism, lens vault was greater in exaggerated lens vault (P < 0.001) and lesser in plateau iris and Thick peripheral iris roll as compared to pupil block mechanism. CONCLUSION: Anterior segment optical coherence tomography may be used for evaluation of underlying primary angle closure mechanism(s) in a patient and tailor the treatment accordingly.

Determinants of corneal biomechanical properties in an adult Chinese population.

PURPOSE: To investigate variations in corneal hysteresis (CH) and corneal resistance factor (CRF) and their ocular and systemic associations in Chinese adults. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 1136 subjects of Chinese origin from an ongoing population-based study. METHODS: All subjects in this population-based study underwent a standardized ocular examination including keratometry (corneal radius of curvature), intraocular pressure (IOP) measurement with Goldmann applanation tonometry, central corneal thickness (CCT), and axial length (AL) assessments. The CH and CRF were measured with the Ocular Response Analyzer. Participants underwent a detailed interview and laboratory investigations that included estimation of nonfasting serum glucose, glycosylated hemoglobin, and lipid profile. MAIN OUTCOME MEASURES: We assessed CH, CRF, and their associations with demographic, ocular, and systemic factors. RESULTS: The mean age of study subjects was 55.3±8.4 years and 51.2% were females. The mean CH and CRF were 10.6±1.5 and 10.1±1.6 mmHg, respectively. Women had higher mean CH (10.8 vs 10.4 mmHg; P<0.001) and CRF (10.4 vs. 9.8 mmHg; P<0.001) than men. After adjusting for age, gender, IOP, CCT, keratometry, AL, and diabetes, CH was negatively associated with age (ß = -0.034; P<0.001), IOP (ß = -0.037; P = 0.01), corneal radius of curvature (ß = -0.963; P<0.001), and AL (ß = -0.106; P = 0.001); and positively associated with female gender (ß = 0.308; P<0.001) and CCT (ß = 0.020; P<0.001). The CRF showed a negative association with age (ß = -0.023; P<0.001) and corneal radius of curvature (ß = -0.771; P<0.001), and was positively associated with female gender (ß = 0.368; P<0.001), IOP (ß = 0.134; P<0.001) and CCT (ß = 0.024; P<0.001). Subjects with diabetes had a higher CH (ß = 0.324; P<0.001) and CRF (ß = 0.396; P = 0.002) compared with those without diabetes. CONCLUSIONS: With advancing age, the CH and CRF in adult Chinese decreased. Women and subjects with diabetes had greater CH and CRF. Corneal biomechanical properties of hysteresis and resistance factor are significantly influenced by IOP, CCT, corneal radius of curvature, and AL.

Intravitreal triamcinolone prior to laser treatment of diabetic macular edema: 24-month results of a randomized controlled trial.

PURPOSE: To report the 24 months outcomes from a clinical trial of intravitreal triamcinolone acetonide (IVTA) plus laser versus laser treatment only in eyes with diabetic macular edema (DME). DESIGN: Prospective, double-masked, randomized, placebo-controlled study. PARTICIPANTS: Eighty-four eyes of 54 participants were entered into the study, with 42 eyes randomly assigned to receive IVTA plus laser and 42 randomly assigned to receive laser treatment alone. Primary end point data were available for 71 (84.5%) eyes at 24 months, with last visual acuity observation carried forward for the remaining eyes. METHODS: Best-corrected logarithm of minimum angle of resolution (logMAR) visual acuity and central macular thickness (CMT) by optical coherence tomography were measured after laser treatment preceded by either IVTA or sham. MAIN OUTCOMES MEASURES: The primary outcome was the proportion of eyes with improvement in visual acuity of 10 letters or more at 24 months. The secondary outcomes were mean visual acuity, requirement for further treatment, change in CMT, and adverse events. RESULTS: At 24 months, improvement of 10 logMAR letters or more was seen in 15 (36%) of 42 eyes treated with IVTA plus laser compared with 7 (17%) of 42 eyes treated with laser only (P = 0.047; odds ratio, 2.79; 95% confidence interval, 1.01-7.67). There was no difference in the mean CMT or mean logMAR visual acuity between 2 groups. At least 1 retreatment was required in the second year of the study in 29 (69%) of 42 IVTA plus laser-treated eyes compared with 19 (45%) of 42 laser only eyes (P = 0.187). Cataracts were removed from 17 (61%) of 28 phakic IVTA plus laser-treated eyes versus 0 (0%) of 27 laser only eyes (P<0.001). Treatment for elevated intraocular pressure was required in 27 (64%) of 42 IVTA plus laser eyes compared with 10 (24%) of 42 laser only eyes (P<0.001). CONCLUSIONS: Treatment with IVTA plus laser resulted in a doubling of improvement in vision by 10 letters or more compared with laser only over 2 years in eyes with DME, but is associated with cataract and raised intraocular pressure.

Prevalence and causes of visual impairment and blindness in an urban Indian population: the Singapore Indian Eye Study.

PURPOSE: To describe the prevalence and causes of visual impairment and blindness in an urban Indian population. DESIGN: Population-based study. PARTICIPANTS: Ethnic Indians aged more than 40 years living in Singapore. METHODS: Participants underwent standardized ophthalmic assessments for visual impairment and blindness, defined using best-corrected visual acuity (BCVA) and presenting visual acuity (PVA), according to US and modified World Health Organization (WHO) definitions. MAIN OUTCOME MEASURES: Unilateral visual impairment or blindness was defined on the basis of the worse eye, and bilateral visual impairment or blindness was defined on the basis of the better eye. Primary causes of visual impairment were determined. RESULTS: A total of 3400 eligible individuals (75.6% response rate) participated. On the basis of US definitions, the age-standardized prevalence was 0.4% for bilateral blindness (≤20/200, better eye) and 3.4% for bilateral visual impairment (<20/40 to >20/200, better eye). Another 0.3% of bilateral blindness and 13.4% of bilateral visual impairment were correctable with refraction. Cataract was the principal cause of best-corrected bilateral blindness (60.0%) and bilateral visual impairment (65.7%). Other major causes of blindness and visual impairment included diabetic retinopathy, age-related macular degeneration, glaucoma, corneal opacity, and myopic maculopathy. CONCLUSIONS: The prevalence of bilateral blindness and visual impairment in Indians living in Singapore is lower than estimates from populations living in India, but similar to estimates obtained from Singapore Malay and Chinese populations. Cataract is the leading cause of blindness and visual impairment. One in 20 cases of bilateral blindness and 1 in 10 cases of bilateral visual impairment are attributable to diabetic retinopathy. These data may have relevance to many ethnic Indian persons living outside India.

Diabetes, hyperglycemia, and central corneal thickness: the Singapore Malay Eye Study.

PURPOSE: To examine the relationship of diabetes and hyperglycemia with central corneal thickness (CCT) in Malay adults in Singapore. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Three thousand two hundred eighty Malay adults ages 40-80 years living in Singapore. METHODS: The study population was selected using an age-stratified random sampling procedure of Malay 40- to 80-year-olds living in the southwestern part of Singapore. Participants had a standardized interview, examination, and ocular imaging at a centralized study clinic. Central corneal thickness was measured with an ultrasound pachymeter, and nonfasting serum glucose and glycosylated hemoglobin (Hb A(1C)) was obtained from all participants. Diabetes was defined as having nonfasting glucose levels of > or =200 mg/dl (11.1 mmol/l), a self-report of diabetic medication use, or physician diagnosis of diabetes. MAIN OUTCOME MEASURES: Central corneal thickness. RESULTS: Of the 3280 (78.7% response) participants, data on CCT were available on 3239 right eyes. Central corneal thickness was normally distributed, with a mean of 541.2 microm. There were 748 persons with diabetes (23.0%). After controlling for age and gender, central corneas were significantly thicker in persons with diabetes than in those without diabetes (547.2 microm vs. 539.3 microm, P<0.001) and, in the total population, with higher serum glucose (539.6, 540.2, 541.3, and 544.4, comparing increasing glucose quartiles; P = 0.023) and higher Hb A(1C) (537.8, 541.0, 541.4, and 545.5, comparing increasing Hb A(1C) quartiles; P<0.001) levels. In multiple linear regression models adjusting for age, intraocular pressure (IOP), body mass index, and axial length, persons with diabetes had, on average, central corneas 6.50 microm thicker than those of persons without diabetes. CONCLUSIONS: This population-based study among Malays showed that diabetes and hyperglycemia are associated with thicker central corneas, independent of age and IOP levels. These findings may have implications for understanding the relationship between diabetes and glaucoma.

Prevalence and risk factors for refractive errors in the Singapore Malay Eye Survey.

PURPOSE: To describe the prevalence and risk factors for myopia and other refractive errors in an urban Malay population in Singapore. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Persons of Malay ethnicity, between 40 and 80 years of age, living in Singapore. METHODS: Refractive error was determined by subjective refraction and if unavailable by autorefraction. Data were analyzed for 2974 adults without previous cataract surgery and who had right eye refraction data. Risk factor data, such as education levels and near work activity, were obtained from a face-to-face interview. MAIN OUTCOME MEASURES: Myopia, defined as spherical equivalent (SE) refraction less than -0.5 diopters (D), astigmatism as cylinder less than -0.5 D, hyperopia as SE greater than 0.5 D, and anisometropia as the difference in SE greater than 1.0 D. RESULTS: The prevalence of myopia in the right eye was 30.7% (9.4% unilateral myopia and 21.3% bilateral myopia), the prevalence of astigmatism in the right eye was 33.3% (95% confidence interval [CI, 33.0-33.5), the prevalence of hyperopia in the right eye was 27.4% (95% CI, 24.7-27.6), and the prevalence of anisometropia was 9.9% (95% CI, 9.7-10.0). There was a U-shaped relationship between increasing age and the prevalence of myopia, which was partially explained by the age-related increase in the prevalence of cataract. In a multiple logistic regression model, female sex, age, higher educational level, and cataract were associated with myopia. Adults with myopia were more likely to have astigmatism (P<0.001) in multivariate analyses. CONCLUSIONS: A quarter of older adult Malay people in Singapore had myopia. Compared with previous reports of similarly aged Singapore Chinese adults, the prevalence of myopia, astigmatism, and anisometropia was lower, whereas the prevalence of hyperopia was similar.

Comparison of central corneal thickness measurements by visante anterior segment optical coherence tomography with ultrasound pachymetry.

PURPOSE: To compare the measurement of the central corneal thickness (CCT) by Visante (Carl Zeiss Meditec, Dublin, California, USA) anterior segment optical coherence tomography (AS-OCT) with ultrasound pachymetry. DESIGN: Population-based, cross-sectional study. METHODS: Participants were part of a population-based study of 3280 Malay subjects aged 40 to 80 years in Singapore. Ultrasound pachmetry of CCT was performed on all participants and approximately 10% underwent further evaluation with AS-OCT. RESULTS: Two hundred and eighty-five consecutive subjects were included, with a mean age of 57.9 (+/- 10.8) years. CCT as measured by ultrasound pachymetry was highly correlated with the equivalent AS-OCT reading (The Pearson correlation coefficient = 0.93, P < .001). However, Bland-Altman analysis showed that CCT as measured by ultrasound pachymetry was significantly higher by 16.5 +/- 11.7 microm (limits of agreement -6.1 to 39.1, P < .001). CONCLUSIONS: CCT measured by Visante AS-OCT was highly correlated with that from ultrasound pachymetry. However, CCT readings by Visante AS-OCT were consistently less than that of ultrasound pachymetry.

Facial Scanning With a Digital Camera: A Novel Way of Screening for Primary Angle Closure.

PURPOSE: We hypothesize that patients with primary angle closure (PAC) have common significant facial characteristics that set them apart from an age-matched, sex-matched, and race-matched control population. The primary objective of this study was to test whether a 3-dimensional (3D) camera could pick up these differences in order to differentiate PAC patients from controls. PATIENTS: A total of 55 patients with PAC and 38 controls were included in the study. MATERIALS AND METHODS: Cases and controls had their facial photographs taken using a 3-dimensional digital camera (3dMdFace System). The facial features in the captured photographs were analyzed using a computer software (Neural Network Toolbox). A regression formula was devised to show whether these facial parameters could be used to distinguish between patients and controls. RESULTS: Thirteen facial parameters were measured, and using a regression formula and neural network classification we were able to mathematically distinguish patients from controls using this method of screening. CONCLUSIONS: PAC patients have distinct facial features that may be differentiated from those of normal individuals mathematically using 3D photography. There is potential for this 3D facial scanning technology in screening for PAC in the general population.

Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion.

PURPOSE: To assess the efficacy of intravitreal 0.5 mg ranibizumab for the treatment of center-involving macular edema secondary to branch retinal vein occlusion (BRVO) over 1 year compared with standard-of-care grid laser. DESIGN: A prospective randomized controlled clinical trial. METHODS: A total of 36 patients with vision loss in 1 eye attributable to macular edema following BRVO were recruited from 5 institutions. Patients were randomized 1:1 to a treatment group that received 6 monthly injections of 0.5 mg ranibizumab and thereafter monthly as needed based on best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessments on optical coherence tomography scans, or a standard-of-care group that received monthly sham injections for the 1-year duration of the study. Grid laser was administered at 13 and 25 weeks in both groups if criteria for laser treatment were met. Main outcome measures included mean change in BCVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores from baseline to month 12. Secondary outcomes included anatomic outcomes and the percentage of patients requiring grid laser in both groups. RESULTS: Mean BCVA change from baseline was significantly greater in the treatment compared with the standard-of-care group at 12 months (12.5 ETDRS letters vs -1.6 ETDRS letters, P = .032). The mean CFT was significantly reduced in the treatment compared with standard-of-care group (361.7 µm vs 175.6 µm, P = .025). At 13 and 25 weeks, more patients in the standard-of-care group (68.4%, 50.0%) received grid laser than in the treatment group (6.7%, 8.3%). No new ocular or systemic adverse events were observed. CONCLUSIONS: Compared with standard grid laser, intravitreal ranibizumab provided significant and sustained benefits in visual acuity gain and anatomic improvement in eyes with macular edema secondary to BRVO.

Can an inexperienced observer accurately plot disc contours using Heidelberg retinal Tomograph?

OBJECTIVE: To examine the reliability of inexperienced observers in plotting optic disc contours on Heidelberg retinal tomography images before and after training. DESIGN: Observational study. PARTICIPANTS: One hundred eyes that were randomly selected from the Singapore Indian Eye Study. METHODS: Both eyes of subjects were imaged with Heidelberg Retina Tomograph 3 (HRT-3; Heidelberg Engineering, Heidelberg, Germany). Optic disc contours were plotted on the same images by 2 new observers on 2 separate occasions, before and after 2-hour standardized training on the skills and tools available to accurately identify and delineate optic disc contours. These plottings were compared with an experienced, trained glaucoma expert (gold standard). Agreement and variability were analyzed by interclass correlation tests and Bland-Altman plots. RESULTS: A total of 182 images (18 excluded because of poor quality) from 89 Indian subjects were included. The mean age was 53.27 ± 7.25 years and 54.8% were male. There was moderate-to-high agreement between pretraining (both new observers) and experienced observer's results (interclass correlation values range, 0.76-0.99). The interclass correlation improved for all the HRT-3 parameters after the 2 new observers were adequately trained. Comparing the interclass correlation values before and after training, the differences for mean retinal nerve fibre layer thickness for Observer 1 and all the HRT-3 parameters for Observer 2 were statistically significant. CONCLUSIONS: This study shows that it is easy to train a new inexperienced observer to plot optic disc contours on HRT images, which translates into improved and acceptable interobserver variability and agreement.

A prospective comparison of chronic primary angle-closure glaucoma versus primary open-angle glaucoma in Singapore.

INTRODUCTION: To describe the optic disc, visual field and ocular characteristics of a consecutive cohort of Asian patients with chronic primary angle-closure glaucoma (CPACG), and compare them with those having primary open-angle glaucoma (POAG). METHODS: In a prospective comparative case series of new patients with POAG or CPACG in Singapore, all patients underwent visual acuity assessment, slit-lamp examination, tonometry, gonioscopy, refraction, Heidelberg Retina Tomograph (HRT) and Humphrey visual field (HVF) assessment. RESULTS: 98 patients were enrolled (POAG n = 48; CPACG n = 50). CPACG patients were significantly older (66.5 ± 9.2 years vs. 64.1 ± 13.5 years; p = 0.027) and mostly female (p = 0.004). CPACG eyes had significantly higher intraocular pressure (26.9 ± 6.9 mmHg vs. 24.5 ± 3.3 mmHg; p = 0.03), shorter axial length (22.89 ± 0.97 mm vs. 24.26 ± 1.79 mm; p < 0.001) and shallower anterior chamber depth (2.60 ± 0.25 mm vs. 3.16 ± 0.48 mm; p < 0.001). HVF mean deviation or pattern standard deviation (PSD) did not differ significantly between POAG and CPACG eyes, but the latter had a lower PSD for a given mean deviation. HRT parameters between the two groups were not significantly different. CONCLUSION: In this study, CPACG eyes had significantly higher presenting intraocular pressure than POAG eyes, but there were no significant differences in optic disc topography. A majority of the patients in both groups had moderate field defects at the time of presentation, followed by severe and then mild defects. The field loss in CPACG eyes was more diffuse than that in POAG eyes.

The prevalence and types of glaucoma in an urban Indian population: the Singapore Indian Eye Study.

PURPOSE: To determine the prevalence and types of glaucoma in an urban Singaporean Indian population. METHODS: The Singapore Indian Eye Study (SINDI) was a population-based, cross-sectional survey that examined 3400 (75.6% response) persons aged 40 to 80 years. Participants underwent a standardized examination including slit-lamp biomicroscopy, Goldmann applanation tonometry, and dilated optic disc assessment. Participants 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 3400 participants, 78 (2.29%) had diagnosed glaucoma, giving an age-standardized prevalence of 1.95% (95% confidence interval [CI], 1.5%-2.5%). The age-standardized prevalence of primary open-angle glaucoma (POAG) was 1.25% (95% CI, 0.89%-1.73%), primary angle-closure glaucoma (PACG) 0.12% (95% CI, 0.04%-0.33%), and secondary glaucoma 0.55% (95% CI, 0.35%-0.86%). The mean IOP among the participants in the normal group in the study population was 15.6 ± 2.6 mm Hg and 17.7 ± 6.1 mm Hg in subjects with glaucoma (P = 0.003). The mean central corneal thickness (CCT) in the normal study population was 540.31 ± 33.79; the mean CCT in subjects with POAG (529.8 ± 30.8 µm) was statistically different from the normal study group (P = 0.003). CONCLUSIONS: The prevalence of glaucoma among Singaporean Indians 40 years of age and older in Singapore was 1.95%, approximately half that of the Chinese and the Malay persons in Singapore. As in other Asian studies, POAG was the main form of glaucoma accounting for nearly 60% of cases.

Duration of anti-tubercular therapy in uveitis associated with latent tuberculosis: a case-control study.

AIM: To study the effect of the duration of anti-tubercular treatment (ATT) on the recurrence of uveitis associated with latent tuberculosis (TB). METHODS: Retrospective review of all consecutive uveitis patients seen at a single, tertiary institution over 9 years with uveitis consistent with TB, positive tuberculin skin test with other causes ruled out, and a minimum of 6 months follow-up after completion of treatment. Clinical characteristics, treatment type, treatment duration and clinical response were recorded. Our main outcome measure was the effect of ATT duration on the recurrence of inflammation. RESULTS: Of the 182 eligible patients, 46 received ATT of ≥ 6 month's duration; 18 patients defaulted and received < 6 months treatment. The patients' mean age was 45.3 ± 13.2 years and most were female (n=118, 57.6%) and of Chinese race (n=104, 50.7%). Patients who completed > 9 months ATT were less likely to develop recurrence compared with those not treated with ATT (OR 0.09; 95% CI 0.01 to 0.76; p=0.027), while adjusting for potential confounders such as patient demographics, anatomical location of uveitis and corticosteroid therapy. CONCLUSION: Patients with uveitis and latent TB treated with ATT of > 9 months duration had an 11-fold reduction in the likelihood of recurrence.

Comparing stereometric parameters between Heidelberg Retinal Tomography 2 and 3 in Asian eyes: the Singapore Malay Eye Study.

PURPOSE: To examine the correlation and agreement of stereometric parameters between Heidelberg Retinal Tomograph version 2 (HRT-2) and HRT-3 in a normal Asian population. METHODS: This was a population-based study using data from the Singapore Malay Eye Study. Participants underwent a standardized and complete ophthalmic examination. A confocal laser ophthalmoscope using HRT-2 was used to take retinal images by 2 trained operators. Disc contours were drawn by a single experienced ophthalmologist. Without modifying the contours, the exact images were then exported and analyzed with HRT-3 software. Paired t tests were used to compare mean differences, whereas interclass correlations and Bland-Altman plots were used to assess agreement and trend of Moorfields regression analysis parameters between HRT-2 and HRT-3. RESULTS: A total of 2960 Malay participants [mean age, 58.3 y (SD 10.9); 50.5% female] were included. Average disc size was 2.15 µm. Interclass correlations and Bland-Altman plots showed good agreement between HRT-2 and HRT-3. However, global disc area, rim area, cup area, cup-disc area ratio, rim-disc area ratio, and rim volume were significantly different between HRT-2 and HRT-3, with all area and rim volume measurements using HRT-2 were approximately 4% larger compared with HRT-3. Analysis of HRT-2 and HRT-3 parameters from different sectors of the scans showed an inconsistent change in measurement values. Cup shape measurement was significantly different in the temporal region compared with the nasal region of the optic nerve head. CONCLUSIONS: There was good correlation between the 2 HRT versions and conversion equations were possible to calibrate HRT-3 parameters from HRT-2 measurements in Asian eyes. However, HRT-2 and HRT-3 showed significant differences in stereometric parameters. Further studies are needed to determine the impact of such differences and in comparative accuracy of HRT-2 versus HRT-3 for diagnosis and monitoring of glaucoma.