Abstract Purpose To determine whether the ocular phenotype in patients with mucopolysaccharidosis type I (MPSI) Hurler is affected by the efficacy of previous haemopoietic stem cell transplantation (HSCT). Design A retrospective cohort study of patients with MPSI who had undergone treatment with HSCT. Methods Ocular phenotype was documented for each patient and compared to levels of biomarkers representing efficacy of previous transplantation. Main outcome measures: Assessment of visual acuity (VA), severity of corneal clouding and the presence of optic neuropathy or retinopathy. Biomarker assessment included dermatan sulphate/chondroitin sulphate (DS/CS) ratio and iduronidase enzyme level. Results Severe corneal clouding was significantly greater in patients with lower iduronidase levels (p = 0.023) and raised DS/CS ratio ( R 2 = 0.28 p = 0.043). Better VA was related to a higher iduronidase levels ( R 2 = 0.15, p = 0.004) and lower DS/CS ratio ( R 2 = 0.38, p = 0.001). Conclusion Improved ocular phenotypes in MPSI are associated with markers signifying efficacy of prior transplant. Early and effective HSCT may result in a better visual prognosis and reduction in ocular complications for patients with MPSI.
Purpose To develop a generative mathematical model of wet age-related macular degeneration (AMD) and model the impact of injections of anti-vascular endothelial growth factor to virtual patients with the condition. Methods We isolated key pathophysiological components of macular degeneration in terms of macular edema development and response to anti-vascular endothelial growth factor (VEGF) agents. We developed mathematical models for each of these components using constants determined from published biological experimentation. Consequently, we combined the mathematical models of the separate components to arrive at an end-to-end model of the evolution of macular edema size and its response to treatment. Results We present a series of simulations based upon our idealised model. Initially, we demonstrate the theoretical change in macular edema height in wet macular degeneration over time without and with anti-VEGF interventions. In our final simulation, we demonstrate the powerful possibilities of virtual clinical trials by simulating a virtual model of a landmark study using our existing mathematical AMD model. Conclusions Using our mathematical modelling based upon known pathological and pharmacological processes we have been able to model the effect of intravitreal injection of an anti-VEGF agent on macular edema from age related macular degeneration. We were subsequently able to mathematically simulate a major clinical trial with results that mirror many key features of the clinical established study. We anticipate that the generative model presented here can evolve to be a useful supportive tool in the challenge to deliver optimal therapy for patients with wet macular degeneration.
Newly formed plant allopolyploids usually have meiosis defect, resulting in chromosomal instability manifested as variation in chromosome number and/or structure. However, not all nascent allopolyploids are equally unstable. The wheat group (Aegilops/Triticum) contains 13 diploid species with distinct genome types. Many of these species can be artificially hybridized to produce viable but sterile inter-specific/intergeneric F1 hybrids, which can generate fertile synthetic allotetraploid wheats after whole genome doubling. Compared with synthetic allotetraploid wheats that contain genome combinations of AADD and S*S*DD (S* refers to related S genomes of a different species), those containing an S*S*AA genome are significantly more stable. However, robustness of the relative stability of S*S*AA genomes is unknown, nor are the phenotypic and fitness consequences during occurrences of secondary chromosomal instability. Here, we report a specific lineage originated from a single individual plant of a relatively stable synthetic allotetraploid wheat with genomes S l S l AA (S l and A subgenomes were from Ae. longissima and T. urartu, respectively) that showed a high degree of transgenerational chromosomal instability. Both numerical chromosome variation (NCV) and structural chromosome variation (SCV) occurred widely. While substantial differences in frequencies of both NCV and SCV were detected across the different chromosomes, only NCV frequencies were significantly different between the two subgenomes. We found that NCVs and SCVs occurred primarily due to perturbed meiosis, allowing formation of multivalents and univalents as well as homoeologous exchanges. Thus, the combination of NCVs and SCVs affected multiple phenotypic traits, particularly those related to reproductive fitness.
Given that depression and anxiety can be comorbid to several treatable eye diseases, it is paramount to understand whether vitreous opacities are also associated with increased risk of well-being and mental health problems. The current systematic review summarises research examining psychological implications of vitreous opacities in adult patients. PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were systematically searched for all articles published up to May 5th 2021. Inclusion criteria included studies that have assessed outcomes related to patients' mental health; well-being; quality of life; coping with the disease; studies exploring patients' experiences/perceptions/cognitions of illness and/or medical treatments related to vitreous opacities. 5 studies were included in this review, with a total of 139 patients [278 eyes] assessed. Patients' age ranged from 32 to 78 years old. Compared with healthy controls, patients with vitreous opacities showed significantly higher levels of symptoms of depression, perceived stress, state anxiety, and trait anxiety. Studies also suggested that patients are more likely to show low vision-related quality of life, and social functioning. Studies also suggested a significant positive effect of medical treatments [e.g. pars plana victretomy] on patients' symptoms of depression and anxiety and on patients' vision-related quality of life. The topic of psychological implications of vitreous opacities is still relatively new in the literature with very preliminary evidence of mental health problems and reduced quality of life associated with this condition.
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