A novel survival prediction signature outperforms PAM50 and artificial intelligence-based feature-selection methods.

The robustness of a breast cancer gene signature, the super-proliferation set (SPS), is initially tested and investigated on breast cancer cell lines from the Cancer Cell Line Encyclopaedia (CCLE). Previously, SPS was derived via a meta-analysis of 47 independent breast cancer gene signatures, benchmarked on survival information from clinical data in the NKI dataset. Here, relying on the stability of cell line data and associative prior knowledge, we first demonstrate through Principal Component Analysis (PCA) that SPS prioritizes survival information over secondary subtype information, surpassing both PAM50 and Boruta, an artificial intelligence-based feature-selection algorithm, in this regard. We can also extract higher resolution 'progression' information using SPS, dividing survival outcomes into several clinically relevant stages ('good', 'intermediate', and 'bad) based on different quadrants of the PCA scatterplot. Furthermore, by transferring these 'progression' annotations onto independent clinical datasets, we demonstrate the generalisability of our method on actual patient data. Finally, via the characteristic genetic profiles of each quadrant/stage, we identified efficacious drugs using their gene reversal scores that can shift signatures across quadrants/stages, in a process known as gene signature reversal. This confirms the power of meta-analytical approaches for gene signature inference in breast cancer, as well as the clinical benefit in translating these inferences onto real-world patient data for more targeted therapies.

Oral Ibuprofen is Associated With Reduced Likelihood of Early Bleb Failure After Trabeculectomy in High-Risk Glaucoma Patients.

PRCIS: Individuals prescribed ibuprofen after trabeculectomy have better postoperative intraocular pressure (IOP) control and a higher chance of bleb survival despite being at a higher risk of scarring. PURPOSE: To investigate the effects of early adjunctive oral ibuprofen treatment on IOP and bleb failure in eyes at high risk of scarring. METHODS: In these retrospective analyses, 288 eyes of 273 patients (mean ± SD age: 68.56 ± 10.47 y; 32.60% females) with primary glaucoma who underwent trabeculectomy/phacotrabeculectomy at the Singapore National Eye Centre between April 2020 and April 2021 with a follow-up duration ≥1 year were included. Of these, 77 (26.7%) eyes deemed to be at high risk of scarring were administered oral ibuprofen ≥3 months postoperatively (mean ± SD ibuprofen administration duration: 4.08 ± 2.28 wk). Participant's IOPs at baseline and at postoperative weeks 1, 2-3; and months 1, 2, 3, 6, and 12 were recorded. Bleb failure was defined as 2 consecutive IOP readings of >21, >18, and >15 mm Hg, and/or requiring remedial postoperative laser or surgery. RESULTS: The ibuprofen group experienced significantly greater postoperative IOP reductions at week 1 [mean difference, 95%CI: -2.89 (-5.22, -0.56) mm Hg] and month 1 [-2.29 (-4.53, -0.05) mm Hg]; and substantially lower odds of bleb failure at the >18 mm Hg [odds ratio, 95% CI: 0.39 (0.20-0.79)] and >15 mm Hg [0.52 (0.29-0.94)] thresholds, compared with the non-ibuprofen group. No differences in adverse ocular hypotony events were observed. CONCLUSION: Early adjunctive oral ibuprofen administered to individuals at high risk of posttrabeculectomy scarring is associated with greater IOP reductions and reduced likelihood of bleb failure. Our results suggest that oral nonsteroidal anti-inflammatory drugs may be a safe way of improving trabeculectomy survival in high-risk eyes.

Optic Neuritis in the Era of NMOSD and MOGAD: A Survey of Practice Patterns in Singapore.

PURPOSE: The Optic Neuritis Treatment Trial was a landmark study with implications worldwide. In the advent of antibody testing for neuromyelitis optica spectrum disease (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), emerging concepts, such as routine antibody testing and management, remain controversial, resulting mostly from studies in White populations. We evaluate the practice patterns of optic neuritis investigation and management by neuro-ophthalmologists and neurologists in Singapore. DESIGN: 21-question online survey consisting of 4 clinical vignettes. METHODS: The survey was sent to all Singapore Medical Council- registered ophthalmologists and neurologists who regularly manage patients with optic neuritis. RESULTS: Forty-two recipients (17 formally trained neuro-ophthalmol-ogists [100% response rate] and 25 neurologists) responded. Participants opted for routine testing of anti-aquaporin-4 antibodies (88.1% in mild optic neuritis and 97.6% in severe optic neuritis). Anti-MOG antibodies were frequently obtained (76.2% in mild and 88.1% in severe optic neuritis). Plasmapheresis was rapidly initiated (85.7%) in cases of nonresponse to intravenous steroids, even before obtaining anti-aquaporin-4 or anti-MOG serology results. In both NMOSD and MOGAD, oral mycophenolate mofetil was the preferred option if chronic immunosuppression was necessary. Steroids were given for a longer duration and tapered more gradually than in idiopathic optic neuritis cases. CONCLUSIONS: Serological testing for NMOSD and MOGAD is considered as a routine procedure in cases of optic neuritis in Singapore, possibly due to local epidemiological features of these conditions. Chronic oral immunosuppression is preferred for the long term, but further research is necessary to establish the efficacy and cost-effectiveness of these practices.

COVID-19 lockdown measures induced severe iron-deficiency anaemia resulting in central retinal vein occlusion and amenorrhea.

During the COVID-19 pandemic, precautionary measures taken by various countries include individual movement restrictions causing significant lifestyle changes and affecting dietary patterns. A 23-year-old woman presented with reduced left eye vision over 1 week and amenorrhea for 4 months. She was diagnosed with severe iron-deficiency anaemia causing central retinal vein occlusion and amenorrhea. During the lockdown, there was a change in her diet with greatly reduced iron intake. Iron is an essential mineral for retina metabolism and function. Iron supplementation was done with improvement in her vision. This case demonstrates the potential impact of lockdown measures on nutrition and health. Education of the general population on maintaining appropriate nutrition during periods of movement restriction is important and that nutritional evaluation and supplementation should be considered in patients with drastic changes in dietary pattern.

Risk factors for early-onset corneal haze after photorefractive keratectomy in an Asian population: Outcomes from the Singapore Armed Forces Corneal Refractive Surgery Programme 2006 to 2013.

PURPOSE: To assess the incidence and risk factors for early corneal haze after myopic photorefractive keratectomy (PRK). SETTING: Tertiary eye center, Singapore. DESIGN: Retrospective case series. METHODS: The refractive results and corneal haze severity 3 months after PRK were analyzed. Eyes were categorized into 4 groups based on haze severity. Multivariate ordinal logistic regression analysis adjusting for age, ethnicity, sex, use of intraoperative mitomycin-C (MMC), preoperative sphere, and preoperative cylinder was performed. RESULTS: The study reviewed data from 177 patients (347 eyes) with a mean age of 22.6 years ± 4.1 (SD). The majority of the patients were Chinese (98.3%) and men (98.3%). The mean preoperative spherical equivalent (SE) was -3.34 ± 1.19 diopters (D). One hundred thirty-five eyes (38.9%) had PRK with MMC. Ten eyes (2.9%) had enhancement surgery. The overall efficacy index was 0.88 and the safety index was 1.07. At 3 months, 187 eyes (53.9%) had no haze, 76 eyes (21.9%) had a haze grade of more than 0 and less than 1, 76 eyes (21.9%) had a haze grade of 1 or more and less than 2, and 8 eyes (2.3%) had grade 2 haze. Higher degrees of myopia (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.13-1.63; P = .001) and astigmatism (OR, 1.56; 95% CI, 1.09-2.24; P = .014) were associated with increased severity of corneal haze, whereas older age (OR, 0.94; 95% CI, 0.88-0.99; P = .023) had a protective effect. CONCLUSION: Myopia and astigmatism were associated with increased severity of haze, and older age was protective against early corneal haze development after PRK in an Asian population. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

The Prevalence and Types of Glaucoma in an Urban Chinese Population: The Singapore Chinese Eye Study.

IMPORTANCE: Glaucoma represents a major public health challenge in an aging population. The Tanjong Pagar Eye Study reported the prevalence and risk factors of glaucoma in a Singapore Chinese population in 1997, which established the higher rates of blindness in this population. OBJECTIVES: To determine the prevalence and associated risk factors for glaucoma among Chinese adults in Singapore and to compare the results with those of the 1997 study. DESIGN, SETTING, AND PARTICIPANTS: In a population-based survey of 4605 eligible individuals, we selected 3353 Chinese adults 40 years or older from the southwestern part of Singapore. Participants underwent examination at a single tertiary care research institute from February 9, 2009, through December 19, 2011. EXPOSURES: All participants underwent slitlamp ophthalmic examination, applanation tonometry, measurement of central corneal thickness, gonioscopy, and a dilated fundus examination. MAIN OUTCOMES AND MEASURES: Glaucoma as defined by the International Society of Geographical and Epidemiological Ophthalmology guidelines and age-standardized prevalence estimates computed as per the 2010 Singapore Chinese census. Blindness was defined as logMAR visual acuity of 1.00 (Snellen equivalent, 20/200 or worse). RESULTS: Of the 3353 respondents, 134 (4.0%) had glaucoma, including primary open-angle glaucoma (POAG) in 57 (1.7%), primary angle-closure glaucoma (PACG) in 49 (1.5%), and secondary glaucoma in 28 (0.8%). The age-standardized prevalence (95% CI) of glaucoma was 3.2% (2.7%-3.9%); POAG, 1.4% (1.1%-1.9%); and PACG, 1.2% (0.9%-1.6%). In a multivariate model, POAG was associated with being older and male and having a higher intraocular pressure. Of the 134 participants with glaucoma, 114 (85.1%; 95% CI, 78.1%-90.1%) were not aware of their diagnosis. Prevalence (95% CI) of blindness caused by secondary glaucoma was 14.3% (5.7%-31.5%), followed by 10.2% (4.4%-21.8%) for PACG and 8.8% (3.8%-18.9%) for POAG. We could not identify a difference in the prevalence of glaucoma compared with the 3.2% reported in 1997 (difference, -0.04%; 95% CI, -1.2 to 1.2; P = .97). CONCLUSIONS AND RELEVANCE: The prevalence of glaucoma among Singapore Chinese likely ranges from 2.7% to 3.9%, with secondary glaucoma being the most visually debilitating type. We could not identify a difference compared with previous studies approximately 12 years earlier. We report a high proportion of previously undiagnosed disease, suggesting the need to increase public awareness of this potentially blinding condition.

Diagnostic Performance of the ISNT Rule for Glaucoma Based on the Heidelberg Retinal Tomograph.

PURPOSE: We determined the accuracy of the inferior > superior > nasal > temporal (ISNT) neuroretinal rim area rule and its variants in adult Asian populations, and evaluated whether disc area impacts its performance characteristics. METHODS: Participants in the Singapore Malay Eye Study (SiMES) and Singapore Indian Eye Study (SINDI) underwent standardized ocular examinations, including optic disc imaging with the Heidelberg retinal tomograph (HRT). Glaucoma was defined using the ISGEO criteria. HRT rim areas in the superior, inferior, nasal, and temporal quadrants were quantified. We determined sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of violating the ISNT rule and 4 variants (I > S > T, I > S, I > T, and combined I > T and S > T). The influence of disc area was analyzed with multivariate marginal logistic regression. RESULTS: There were 6112 participants (mean age: 57.6 ± 10.3 years). Glaucoma was present in 194 individuals (3.2%). Among 11,840 eyes, 232 (93.2%) of 249 glaucomatous eyes and 9768 (84.3%) of 11,591 nonglaucomatous eyes, violated the ISNT rule. The ISNT rule had highest sensitivity (93.5%), but lowest specificity (15.7%); I > T had highest specificity (98.2%), but low sensitivity (7.4%). For all variants, PPVs were low (2.1%-8.4%) and NPVs were high (97.9-99.1%). Larger disc area was associated with reduced specificity for the ISNT rule (P < 0.001), and reduced sensitivity (P = 0.01) and increased specificity for I > S > T (P < 0.05). PPV increased (P < 0.05) and NPV decreased (P < 0.001) with increasing disc area. CONCLUSIONS: The ISNT rule based on HRT has high sensitivity, and the I > T, S > T, and combined I > T and S > T variants have high specificity. Disc area influences sensitivity, specificity, PPV, and NPV of the ISNT rule and its variants. TRANSLATIONAL RELEVANCE: The high sensitivity of the ISNT rule, and high specificities of its variants, may have potential utility when used in combination with other HRT algorithms for glaucoma assessment.

Acceptance, attitudes, and beliefs of Singaporean Chinese toward an ocular implant for glaucoma drug delivery.

PURPOSE: We investigated patients' attitudes and perceptions toward a subconjunctival implant as a novel ocular drug delivery method for glaucoma. METHODS: We recruited 344 Chinese patients with primary open angle or angle closure glaucoma currently on topical antiglaucoma medication for a minimum of six months from specialist glaucoma clinics. Sociodemographic data, and information about patients' general and ocular health were collected. Beliefs about medicines, glaucoma, eye drops, and self-reported adherence were assessed by trained interviewers using validated questionnaires. A description about the implant was provided and patients subsequently were assessed on their understanding and acceptance. RESULTS: Of the 344 Chinese patients enrolled, 216 (62.8%) would accept the implant as a replacement for their current eye drops. Of those who accepted the implant, 99 (45.8%) were willing to accept it at similar costs, while 40 (18.5%) and 20 (9.3%) patients were willing to pay 1.5 and 2 times the cost of their present medication, respectively. Patients who accepted the implant had more severe glaucoma (P = 0.015) and felt that the implant was more helpful than eye drops (P < 0.001). Beliefs toward medicines, glaucoma, eye drops, self-reported adherence, and sociodemographic factors did not have a significant impact on the patients' decisions. CONCLUSIONS: An ocular drug implant would be an acceptable alternative to topical eye drops for subgroups of glaucoma patients.