Aqueous humour protein dysregulation in Asian eyes with primary open angle glaucoma.

The pathophysiology of Primary Open Angle Glaucoma (POAG) remains poorly understood. Through proteomic analysis of aqueous humour (AH) from POAG patients, we aim to identify changes in protein composition of these samples compared to control samples. High resolution mass spectrometry-based TMT6plex quantitative proteomics analysis is performed on AH samples collected from POAG patients, and compared against a control group of patients with cataracts. Data are available via ProteomeXchange with identifier PXD033153. 1589 proteins were quantified from the aqueous samples using Proteome Discoverer version 2.2 software. Among these proteins, 210 were identified as unique master proteins. The proteins which were up or down-regulated by ±3 fold-change were considered significant. Human neuroblastoma full-length cDNA clone CS0DD006YL02 was significantly upregulated in patients with severe POAG on >2 medications, while actin, cytoplasmic 1, V2-7 protein (fragment), immunoglobulin-like polypeptide 1 and phosphatidylethanolamine-binding protein 4 were only present in these patients with severe POAG on >2 medications. Beta-crystallin B1 and B2, Gamma-crystallin C, D and S were significantly downregulated in the severe POAG ≤2 glaucoma medications group. Beta-crystallin B2, Gamma-crystallin D and GCT-A9 light chain variable region (fragment) were significantly downregulated in the non-severe POAG group. Actin, cytoplasmic 1 was significantly upregulated in subjects with severe POAG who required more than 2 glaucoma medications. Crystallins (Beta-crystallin B1 and B2, Gamma-crystallin C, D and S) were significantly downregulated in subjects with severe POAG who required less than 2 glaucoma medications.

Multi-center evaluation of artificial intelligent imaging and clinical models for predicting neoadjuvant chemotherapy response in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumors, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumors' response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC. METHODS: The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on deep learning (DL). Clinical parameters were included to build a final prognostic model. RESULTS: The best performing models were based on space-resolved and DL approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855). CONCLUSIONS: Radiomics features extracted from diagnostic CT augment the predictive ability of pCR when combined with clinical features. The novel space-resolved radiomics and DL radiomics approaches outperformed conventional radiomics techniques.

Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery.

BACKGROUND: To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects. METHODS: Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA). RESULTS: There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334-0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were - 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively. CONCLUSIONS: No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.

Management of Nonunion and Malunion After Primary Mandibular Condylar Fracture Treatment: A Review and Recommendations.

PURPOSE: After primary treatment of mandibular condylar fractures, nonunion and malunion can result in considerable malocclusion and temporomandibular joint dysfunction owing to the integral role the condylar head plays in the temporomandibular joint. At present, the choice and timing of treatment are highly heterogeneous. The purpose of this study was to evaluate the current literature to identify possible pitfalls, discuss available treatment options, and make recommendations. METHODS: The electronic databases PubMed, MEDLINE, PROSPERO, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase were searched for content matching mandibular condylar fracture "revision surgery," "secondary surgery," "refracture," "malunion," and "malunion osteotomy." Articles in English, limited to human adults, published in the past 10 years, with abstracts and full text available and appropriate study designs, were included. RESULTS: A total of 101 articles were retrieved for analysis, and 4 articles were included. Because of heterogeneity in these studies, a pooled analysis could not be performed. CONCLUSIONS: Surgery can be considered as primary treatment of condylar fractures, and early detection of complications allows for early intervention, leading to better outcomes. Treatment of temporomandibular joint dysfunction is highly heterogeneous and ranges from nonsurgical measures to joint reconstruction. Unilateral malocclusion can often be corrected with unilateral surgery, but bilateral surgery may be indicated in select cases. Bilateral deformities often require bilateral mandibular surgery, but in cases with preserved symmetry, maxillary surgery can be performed.

Imaging and treatment with 68Gallium and 177Lutetium-DOTATATE in a rare SSTR2 and ESWR1-CREM fusion positive undifferentiated round cell tumour of the lung.

The authors present a 45-year-old lady with a rare undifferentiated round cell tumour of the lung with a ESWR1-CREM fusion gene that progressed despite multiple lines of therapy. The tumour was Somatostatin Receptors Type 2 (SSTR2) positive and avid on 68Gallium-DOTATATE imaging. This allowed for novel treatment with Peptide Receptor Radionuclide Therapy (PRRT) using 177Lutetium-DOTATATE after all other standard of care options were exhausted.

Case of flank pain from ureteral injury after lumbar laminectomy.

We present a case of an iatrogenic complete left proximal ureteric injury after a lumbar 1 laminectomy and intradural tumour excision and lumbar 4/5 transforaminal lumbar interbody fusion. Initial management included a percutaneous nephrostomy for urinary diversion followed by definitive urinary reconstruction with an ileal ureter.

Visual field progression 8 years after trabeculectomy in Asian eyes: results from The Singapore 5-Fluorouracil Study.

BACKGROUND/AIMS: This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. METHODS: This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). RESULTS: 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. CONCLUSION: In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression.

Longitudinal Changes in Bleb Height, Vascularity, and Conjunctival Microcysts After Trabeculectomy.

OBJECTIVE: The objective of this article was to study longitudinal changes in bleb morphology (presence of microcysts and bleb height and vascularity) in subjects enrolled in the Singapore 5-Fluorouracil (5-FU) trabeculectomy study. STUDY DESIGN: Retrospective subgroup analysis of a randomized controlled trial. MATERIALS AND METHODS: Following trabeculectomy with either 5-FU or placebo, subjects were reviewed at day 1, weeks 1, 2, and 3, and months 3, 6, 9, 12, 16, 20, 24, 28, 32, and 36 and intraocular pressure (IOP), presence of microcysts and bleb height and vascularity graded and recorded. Statistical analyses were used to investigate baseline factors (demographics, eye drops use, IOP, treatment type, and comorbidities) that might account for long-term bleb changes and assess the influence of bleb morphology on mean, maximum, minimum, and variation in IOP following trabeculectomy. RESULTS: One hundred fifty-nine (61.2%) subjects completed follow-up and 71 subjects (44.7%) received 5-FU. Proportion of subjects with microcysts increased posttrabeculectomy till weeks 3 and 6 in 5-FU and placebo-treated eyes, respectively, before decreasing. Presence of microcysts at day 1 and week 2 was associated with lower mean (P=0.027 to 0.033), maximum (P=0.040), and minimum IOP (P=0.010). Mean bleb height decreased over 36 months and at months 20 and 36 was associated with maximum (P=0.031) and minimum IOP (P=0.032), respectively. Mean bleb vascularity decreased till month 9 and remained fairly constant after. CONCLUSIONS: Microcysts seen early posttrabeculectomy is associated with lower IOP. Blebs reduce in height as they remodel and the relationship between bleb vascularity and IOP is complex.

Traumatic optic neuropathy: a review.

The aim of this article is to evaluate current literature on investigation and management of traumatic optic neuropathy (TON), propose recommendations for diagnosis and management, and explore novel future treatments. TON, though uncommon, causes substantial visual loss. Without clear guidelines, there is much ambiguity regarding its diagnosis and management. Investigation and treatment (conservative, medical, surgical, and combined) vary widely between centers. Electronic databases PubMed, MEDLINE, PROSPERO, CENTRAL, and EMBASE were searched for content that matched "Traumatic optic neuropathy." Articles with abstracts and full text available, published in the past 10 years, written English and limited to human adults, were selected. All study designs were acceptable except case reports and case series with fewer 10 patients. All abstracts were then evaluated for relevance. References of these studies were evaluated and if also relevant, included. A total of 2,686 articles were retrieved and 43 examined for relevance. Of these, 23 articles were included. TON is a clinical diagnosis. Visual-evoked potential is useful in diagnosis and prognosis. Computed tomography demonstrates canal fractures and concomitant injuries. Magnetic resonance images should be reserved for select and stable patients. Conservative treatment is appropriate in mild TON. Steroids are of questionable benefit and may be harmful. Surgery should be reserved for patients with radiological evidence of compression and individualized.

Analysis of Changes in Refraction and Biometry of Atropine- and Placebo-Treated Eyes.

PURPOSE: To analyze changes in refraction and associated biometric changes in atropine- and placebo-treated eyes in the Atropine for Treatment of Myopia study (ATOM1). METHODS: A total of 400 myopic children, aged 6 to 12 years, were assigned randomly to receive 1% atropine or a placebo agent in one eye daily for 2 years, after which drops were stopped and children monitored for another year. Cycloplegic autorefraction, A-scan biometry, and automated keratometry were performed at the initial visit, 2 weeks (baseline), and at 4, 8, 12, 16, 20, 24, 30, and 36 months. RESULTS: A total of 313 children (78.3%) completed the study. In placebo-treated eyes, there was myopic progression of -1.55 diopters (D), between baseline and 36 months, associated with reductions in corneal curvature (K; -0.13 D) and anterior chamber depth (ACD; -0.17 mm) and increases in lens thickness (LT; 0.05 mm), vitreous chamber depth (VCD; 0.65 mm), and axial length (AL; 0.53 mm). Multivariate analysis of change in spherical equivalent demonstrated that the hyperopic shift (0.20 D) noted in atropine-treated eyes between baseline and 4 months, and the myopic rebound (-0.74 D) noted between 24 to 30 months when atropine was stopped, were associated with a reduction and increase in VCD and AL, respectively, after adjusting for age and sex. Changes in K, ACD, and LT were less relevant. Between 4 and 24 months, atropine-treated eyes demonstrated gradual myopic progression (-0.40 D), accompanied by reduction in K (-0.06 D) and ACD (-0.07 mm) and increase in VCD (0.13 mm) and AL (0.06 mm). CONCLUSIONS: Atropine appeared to slow myopia progression mainly by reducing or slowing the growth in VCD, and thereby AL. (ClinicalTrials.gov number, NCT00371124.)