ABSTRACT
Purpose: Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research. Methods: Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets. Results: Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated. Conclusions: This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.
Subject(s)
Cataract Extraction , Exfoliation Syndrome , Lens, Crystalline , Epithelium/metabolism , Exfoliation Syndrome/genetics , Exfoliation Syndrome/pathology , Humans , Lens, Crystalline/metabolism , Sequence Analysis, RNAABSTRACT
BACKGROUND: Dry eye disease (DED) is a common condition frequently encountered yet underdiagnosed in primary care. It can lead to significant morbidity, affecting quality of life. The causes are numerous, while treatment is continually changing. OBJECTIVE: This article provides essential information on DED for the general practitioner. While the concept of DED can appear to be simple, several issues need to be considered before arriving at the diagnosis and initiating treatment. This article discusses the approach to DED based on pathophysiology, symptoms and examination, leading to appropriate and effective treatment. DISCUSSION: While DED appears to be underdiagnosed, there has been an increased effort to provide validated symptom questionnaires, such as the ocular surface disease index and five-item dry-eye questionnaire, to aid in diagnosing and grading the severity of DED. This has helped with deciding on best management and appropriate treatment options for the patient.
Subject(s)
Dry Eye Syndromes , General Practice , Algorithms , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/therapy , Humans , Quality of Life , Surveys and QuestionnairesSubject(s)
Administration, Ophthalmic , Anesthetics, Local/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Eye Pain/prevention & control , Injections, Intraocular/methods , Lidocaine/administration & dosage , Tetracaine/administration & dosage , Adult , Eye Pain/etiology , Humans , Intravitreal Injections/adverse effects , Macular Edema/drug therapy , Pain Measurement , Prospective Studies , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
Aflibercept has been listed on the Australian Pharmaceutical Benefit Scheme for the past year for neovascular age-related macular degeneration. Since that time there have not been any reports of delayed onset panuveitis. We present two cases of anterior and posterior uveitis that have occurred 4â weeks or more after first intravitreal injection of aflibercept. Both patients had received other vascular endothelial growth factor inhibitors prior to aflibercept administration without signs of inflammation and both cases had sterile endophthalmitis. On resolution of the inflammation the patients were recommenced on ranibizumab without further incident.
