To study the effect of the duration of anti-tubercular treatment (ATT) on the recurrence of uveitis associated with latent tuberculosis (TB).
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.
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.
Patients with uveitis and latent TB treated with ATT of > 9 months duration had an 11-fold reduction in the likelihood of recurrence.
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.
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).
Prospective, ...double-masked, randomized, placebo-controlled study.
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.
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.
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.
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).
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.
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.
Purpose To examine the association of corneal arcus to cardiovascular disease (CVD) in an adult, ethnic Indian population. Design Population-based cross-sectional study. Methods Population-based ...study of ethnic South Asian Indians 40 to 80 years of age in Singapore from June 2007 through March 2009. We obtained a 75.5% response rate (3397/4497). All participants underwent standardized interview and systemic and ocular examinations, followed by nonfasting blood sampling. Corneal arcus was detected using a standardized slit-lamp examination. The main outcome measure was CVD, defined from a self-reported history of previous myocardial infarction, angina, or stroke. Results Corneal arcus, found in 1701 (50.1%) of 3397 participants, was associated with older age (odds ratio OR, 3.07; 95% CI, 2.78 to 3.40; P < .001), male gender (OR, 2.17; 95% CI, 1.81 to 2.62; P < .001), higher levels of total cholesterol (OR, 1.14; 95% CI, 1.05 to 1.24; P = .002), hypertension (OR, 1.14; 95% CI, 1.05 to 1.24; P = .013), and cigarette smoking (OR, 1.59; 95% CI, 1.25 to 2.03; P < .001). Corneal arcus was associated with CVD (OR, 1.31; 95% CI, 1.02 to 1.7; P = .0038) independent of the above-named cardiovascular risk factors. Participants with low-risk Framingham scores were more likely to be associated with CVD if they had corneal arcus (men: OR, 2.02; 95% CI, 1.20 to 3.40; P = .008; women: OR, 2.78; 95% CI, 1.36 to 3.01; P < .001). Corneal arcus was associated with CVD independent of the Framingham score (men: Akaike information criterion, 1524.39 for Framingham Score and corneal arcus vs 1527.38 for Framingham Score alone; women: 1000.14 vs 1003.54, respectively). Conclusions Corneal arcus is associated with CVD, independent of risk factors in ethnic Indian adults, even in those at low risk for vascular disease.
Purpose To assess the determinants of image quality of Heidelberg Retina Tomography II (HRT II) and its association with optic disc parameters in a population-based setting. Design Population-based, ...cross-sectional study involving 3280 (78.7% response) Asian Malays aged 40 to 80 years. Methods Three thousand fifty-six participants completed the HRT II test. Image quality was assessed using the mean pixel height standard deviation generated by the HRT II, with lower mean pixel height standard deviation indicating higher quality. Participants underwent an interviewer-administered questionnaire and a standardized ophthalmic examination, including visual acuity, applanation tonometry, gonioscopy, refraction, automated perimetry, and lens and fundus photography. Results The mean (standard deviation) and median of mean pixel height standard deviation in the study population were 34 (34) and 23 μm respectively. In multivariate regression models, older age and the presence of visual impairment, blindness, high myopia, and cataract were significantly associated with greater mean pixel height standard deviation ( P < .05 for all). People with a higher mean pixel height standard deviation were more likely to have smaller rim area and greater cup depth. Conclusion People who are older or have high myopia, visual impairment, blindness, or cataract are more likely to have poor HRT II image quality. Poorer image quality is in turn associated with smaller optic rim area and greater cup depth. These data provide useful information when the HRT instrument is used for diagnosing glaucoma in the general population.
In patients with polymyalgia rheumatica with relapse during glucocorticoid tapering, interleukin-6 receptor antagonist sarilumab increased disease remission and reduced glucocorticoid exposure at 1 ...year.
Abstract
Introduction/Background
Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) ...pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing).
Objectives
To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD.
Methods
STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to <75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose LD, n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388).
Results
Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of –32.1% (95% CI: –43.9, –20.3; P<0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, –27.3 (95% CI: –39.1, –15.6; P<0.0001); 125 mg, –22.2 (95% CI: –34.0, –10.4; P=0.0002); and 62.5 mg, –30.2 (95% CI: –41.9, –18.5; P<0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P<0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS ≥4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified.
Conclusions
In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups.
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.
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.
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%).
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.
