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  • Exploring metabolic biomarkers in primary and chemoreduced retinoblastoma with patient outcomeThis link opens in a new windowApr 11, 2025
    Aims

    The goal of this study is to identify the pathological findings and expression of metabolic markers (GLUT-1, PDK-1 and PGC1α) in the tumour microenvironment of both primary and chemoreduced retinoblastoma (Rb) and to correlate with clinicopathological parameters and patient outcome.

    Methods

    81 prospective cases were included, in which 53 cases underwent primary enucleation and 28 cases received chemotherapy before enucleation. Immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression pattern of metabolic markers in primary and chemoreduced Rb.

    Results

    Tumour microenvironment and histopathological findings were different for both primary and chemoreduced Rb. Increased immunohistochemical expression of GLUT-1, PDK-1 and PGC1α was found in primary Rb as compared with chemoreduced Rb. mRNA expression was also found to be upregulated in primary Rb compared with chemoreduced. On univariate analysis, the presence of more than one histopathological high-risk factor (HRFs>1) and PDK-1 immunoexpression was statistically significant with overall survival. On prognostication in primary and chemoreduced cases with hypoxia, we found increased HR in cases with retrolaminar ON invasion, presence of more than one HRF, and presence of PDK-1 and PGC-1α immunoexpression.

    Conclusions

    This is the first of its kind study predicting a relevant role of the metabolic markers in primary and chemoreduced Rb with prognostic significance. Differential expression of these markers in both groups of Rb is a novel finding and might be an interesting and beneficial target for the management of Rb patients.

  • Neuropathic corneal pain following refractive surgery: risk factors, clinical manifestations, imaging and proteomic characteristicsThis link opens in a new windowApr 10, 2025
    Background/aims

    To identify the risk factors for neuropathic corneal pain (NCP) following corneal refractive surgery and to report its clinical manifestations, imaging and proteomic characteristics.

    Methods

    This 1 year prospective cohort study included 100 eyes that underwent small incision lenticule extraction (SMILE) or laser-assisted in situ keratomileusis (LASIK). Ocular surface assessments, in-vivo confocal microscopy scans, tear neuromediators and proteomics analyses were performed. NCP was assessed using the ocular pain assessment survey. Univariate and multivariate analyses were conducted to identify the risk factors associated with postoperative NCP.

    Results

    The incidence of NCP was 13.3% and 10.5% after SMILE and LASIK, respectively (p=0.70). In SMILE, preoperative manifest refractive spherical equivalent (MRSE) and spherical power (both p=0.02) were significantly higher in the NCP compared with the non-NCP group. In LASIK, NCP eyes had a significantly lower corneal nerve fibre length (CNFL) (p=0.02), lower nerve fractal dimension (p=0.003), higher nerve fibre width (p=0.04) and larger neuroma area (p=0.04) than non-NCP eyes. In SMILE, higher preoperative MRSE was a significant risk factor for postoperative NCP (95% CI: 0.48—1.96, p=0.04). An MRSE greater than –8.0 diopter was 9.57 times more likely to develop postoperative NCP (OR=9.57, p=0.002). In LASIK, lower preoperative corneal nerve fibre density (95% CI:0.13—1.11, p=0.05) and CNFL (95% CI:0.09—1.25, p=0.05) were significant risk factors for postoperative NCP. Significant increases in tear nerve growth factor, calcitonin gene-related peptide, Frizzled class receptor 7 and nucleoside-diphosphate kinase three were observed in postoperative NCP.

    Conclusions

    The reported characteristics and risk factors would identify patients susceptible to NCP after corneal refractive surgery.

  • Meibum and lid margin microbiome in eyes with chalazion: exploring an infectious aetiologyThis link opens in a new windowApr 7, 2025
    Purpose

    The current study evaluated the meibum and lid margin microbiome of eyelids with chalazion and compared it with contralateral uninvolved eyelids and healthy controls.

    Methods

    Chalazion contents (group 1) and expressed meibum swabs from the lid margins of seven patients with chalazion (mean age 29±12 years; >6 weeks chalazia duration) and age-matched healthy controls were sequenced using next-generation 16S rDNA V3-V4 variable region sequencing. The meibum from the contralateral eye of patient with chalazion served as sample control (group 2), and healthy individuals served as negative control (group 3). The contents were also plated using conventional culture techniques.

    Results

    Meibomian glands expressed thick turbid meibum in the area of chalazion in five out of seven eyelids. Contralateral uninvolved eyelids and healthy control glands were expressible with clear meibum. The mean Schirmer I value was 24.6±4.9 mm. Lid margin and meibum microbiome profiling revealed significant differences between the patients (involved or uninvolved sides) and healthy controls. The predominant phyla were Proteobacteria, Bacteroidota and Actinobacteria in all three groups. Acinetobacter, Moraxella and Paracoccus were the predominant genera in groups 1 and 2. Significant differences were noted in the predominant genera between group 3 versus groups 1 and 2. Principal coordinate analysis revealed overlap between groups 1 and 2, whereas group 3 had a distinct cluster. None of the culture media (for aerobic, anaerobic bacteria and fungus) showed any bacterial growth.

    Conclusion

    In patients with unilateral chalazion, involved and uninvolved eyelids share similar lid margin and meibum microbiome but differ from the healthy controls.

  • Adverse renal events between ranibizumab and aflibercept in patients with diabetic macular oedema in Taiwan: a comparative cohort studyThis link opens in a new windowApr 3, 2025
    Aims

    To assess and compare the risk of adverse renal events among patients with diabetic macular oedema (DME) who were treated with either intravitreal ranibizumab or aflibercept in Taiwan.

    Methods

    We conducted a population-based retrospective cohort study and employed a target trial emulation framework using Taiwan’s National Health Insurance Database from 2011 to 2018.

    Patients aged over 20 years diagnosed with DME and receiving treatment with either intravitreal aflibercept or ranibizumab were included. We applied propensity score methods to ensure balance in the baseline characteristics between the two treatment groups. The primary outcomes were the adverse renal events, specifically acute renal injury and hospitalisation due to renal events. We employed Cox proportional hazards models to estimate the HRs associated with these outcomes.

    Results

    A total of 6330 patients receiving ranibizumab and 1258 patients receiving aflibercept were included in this study. The incidence rates of adverse renal events were 102.2 and 138.7 per 1000 person-years for ranibizumab and aflibercept, respectively. Patients treated with intravitreal aflibercept had a significantly higher risk of experiencing a composite of adverse renal events (HR: 1.42; 95% CI: 1.24 to 1.63), compared with those treated with ranibizumab, and specifically also a higher risk of acute kidney injury (HR: 1.32; 95% CI: 1.08 to 1.63) and hospitalisation due to renal events (HR: 1.43; 95% CI: 1.25 to 1.64).

    Conclusion

    In comparison to ranibizumab, the intravitreal use of aflibercept was associated with a greater risk of adverse renal events. These findings provide a solid foundation for future studies to validate these results further.

  • The eye as a window to oral and pain symptoms in Sjögrens diseaseThis link opens in a new windowApr 3, 2025
    Background

    To investigate whether certain dry eye (DE) metrics relate to oral and pain manifestations of Sjögren’s disease (SjD).

    Methods

    Secondary analysis of the Sjögren’s International Collaborative Clinical Alliance dataset containing 1541 individuals with 2016 American College of Rheumatology/European League Against Rheumatism defined SjD. Binary logistic regression analyses examined which of 13 DE features related to various extraocular metrics.

    Results

    The mean age of the population was 52±13.5 years; 45% identified as white and 94% as women. Heterogeneity in DE symptoms and signs was noted in individuals with SjD, with approximately one-third of individuals reporting significant spontaneous and/or evoked pain using various descriptors and indicating certain triggers, and approximately half having low tear production. Similarly, heterogeneity was noted with respect to oral and pain complaints, with extraocular pain symptoms found in approximately one-third of the population. Different ocular phenotypes aligned with different extraocular findings. Specifically, grittiness or scratchiness in the eyes (OR=1.6), blurred vision (OR=1.4) and low tear production (OR=1.8) most closely aligned with oral dryness (‘Does your mouth feel dry?). On the other hand, burning or stinging in the eyes (OR=1.6), discomfort in low humidity (OR=1.2) and the absence of DE signs (normal tear production, OR=0.7; lack of ocular surface staining, OR=0.6) most closely aligned with pain outside the eye (‘Do you experience persistent or frequent burning discomfort?’).

    Conclusions

    Our findings suggest heterogeneity in SjD ocular presentations that predict extraocular features of disease and hint at mechanisms that underlie heterogeneity, namely divergent neurosensory processes.

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