Correlations between the Michigan Retinal Degeneration Questionnaire and visual function parameters in patients with retinitis pigmentosa.

PURPOSE: To validate the use of best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD; the difference between BCVA and LLVA), mean macular sensitivity and fixation stability as parameters of vision-related quality of life based on the novel Michigan Retinal Degeneration Questionnaire (MRDQ) in retinitis pigmentosa (RP) patients. METHODS: In this prospective cross sectional study, 30 patients with RP (47% female) were included with a median age of 41.0 years (interquartile range: 24.1-58.3 years). BCVA, LLVA and LLD were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Mesopic microperimetry was performed to measure mean macular sensitivity and fixation stability. Patients completed a Dutch translation of the MRDQ which results in an experienced disability (Θ-)score of seven domains. Spearman's rank correlation was used. RESULTS: BCVA correlated significantly to the MRDQ domain of central vision (r = 0.657; p < 0.001) and colour vision (r = 0.524; p = 0.003). Lower LLVA significantly correlated to higher experienced disability in the MRDQ domains for central vision (=0.550; p = 0.002) and contrast sensitivity (r = 0.502; p = 0.005). LLD was significantly correlated to the MRDQ domains of scotopic function (r = -0.484; p = 0.007) and mesopic peripheral function (r = -0.533; p = 0.002). Lower mean macular sensitivity was significantly associated with high experienced disability in all domains except for photosensitivity. CONCLUSIONS: The majority of the MRDQ domains is strongly associated with visual function parameters. These findings show that visual function measurements, especially LLVA, LLD and mean macular sensitivity on microperimetry, reflect vision-related quality of life and can be used as relevant outcome measures in clinical trials for RP.

Systematic Review and Meta-Analysis of the Influence of Genetic Variation on Ototoxicity in Platinum-Based Chemotherapy.

OBJECTIVE: The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity. DATA SOURCES: Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed. REVIEW METHODS: Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI). RESULTS: From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols. CONCLUSION: Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.

Exploring the choroidal vascular labyrinth and its molecular and structural roles in health and disease.

The choroid is a key player in maintaining ocular homeostasis and plays a role in a variety of chorioretinal diseases, many of which are poorly understood. Recent advances in the field of single-cell RNA sequencing have yielded valuable insights into the properties of choroidal endothelial cells (CECs). Here, we review the role of the choroid in various physiological and pathophysiological mechanisms, focusing on the role of CECs. We also discuss new insights regarding the phenotypic properties of CECs, CEC subpopulations, and the value of measuring transcriptomics in primary CEC cultures derived from post-mortem eyes. In addition, we discuss key phenotypic, structural, and functional differences that distinguish CECs from other endothelial cells such as retinal vascular endothelial cells. Understanding the specific clinical and molecular properties of the choroid will shed new light on the pathogenesis of the broad clinical range of chorioretinal diseases such as age-related macular degeneration, central serous chorioretinopathy and other diseases within the pachychoroid spectrum, uveitis, and diabetic choroidopathy. Although our knowledge is still relatively limited with respect to the clinical features and molecular pathways that underlie these chorioretinal diseases, we summarise new approaches and discuss future directions for gaining new insights into these sight-threatening diseases and highlight new therapeutic strategies such as pluripotent stem cell‒based technologies and gene therapy.

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection.

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways.

The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.