Subject(s)
Delivery of Health Care/organization & administration , Glaucoma/therapy , Patient Care Team/organization & administration , Practice Guidelines as Topic/standards , Evidence-Based Medicine , Humans , Intraocular Pressure , Ocular Hypertension/therapy , Ophthalmology/organization & administration , Ophthalmology/standards , Optometry/organization & administration , Optometry/standards , Societies, MedicalABSTRACT
BACKGROUND: Despite increasing knowledge of the genetic pathophysiology of glaucoma, mutations in known genes account for less than 15% of disease. Gene screening predominantly remains a research tool rather than an essential part of the clinical work-up. We aimed to determine the mutational spectrum and frequency in the genes implicated in glaucoma, in a range of glaucoma and 'glaucoma suspect' (GS) participants, with a positive family history. METHODS: Observational large case series. One hundred fifteen patients recruited from public hospital and private clinics had diagnoses of GS, ocular hypertension, pseudoexfoliative glaucoma (PXG) or primary open-angle glaucoma (POAG), and at least one affected family member. In a university laboratory, DNA samples were screened for mutations in all coding exons of MYOC and CYP1B1, and OPTN (exons 4, 5 and 16). WDR36 (exons 1, 4, 5, 8, 11, 13 and 17) was screened in those with CYP1B1 changes. LOXL1 risk variants were screened in PXG pedigrees. Cascade screening of family members was undertaken. RESULTS: Seven out of one hundred fifteen (6.1%) individuals had at least one pathogenic or hypomorphic CYP1B1 allele associated with GS, POAG (5) and PXG phenotypes, including two novel sequence variations (p.Ser6Gly, p.Val243Leu). No pathogenic MYOC change was detected. Five individuals (4.3%) carried an OPTN sequence variation. Three of the seven with CYP1B1 changes had polygenic changes. CONCLUSIONS: Mutational analysis of known glaucoma genes in a mixed glaucoma population replicates the reported frequency of pathogenic CYP1B1 changes. Heterozygous CYP1B1 changes occurred at a greater frequency than other genes. Glaucoma pathogenesis in the clinic setting is genetically heterogeneous and may be polygenic.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Glaucoma, Open-Angle/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amino Acid Oxidoreductases/genetics , Cell Cycle Proteins , Cytochrome P-450 CYP1B1 , Cytoskeletal Proteins/genetics , DNA Mutational Analysis , Exons/genetics , Eye Proteins/genetics , Female , Gene Frequency , Glycoproteins/genetics , Humans , Intraocular Pressure , Male , Membrane Transport Proteins , Middle Aged , Pedigree , Phenotype , Transcription Factor TFIIIA/genetics , Young AdultABSTRACT
A 90-year-old woman developed a large circular capsulorhexis-like defect in Descemet's membrane as a complication of small incision cataract surgery. Nine months post-surgery, in vivo confocal microscopic examination of the temporal mid-peripheral cornea revealed an endothelial cell density of 934 +/- 69 cells/mm2 (normal range 1566-3088 cells/mm2). Endothelial pigmented deposits were visible as scattered hyper-reflective areas on the posterior endothelial surface. Descemet's folds were also noted. In vivo confocal microscopy performed 3 years later showed the temporal mid-peripheral corneal endothelial density (in the region of the break) was 948 +/- 66 cells/mm2. A reduction of endothelial polymegathism and pleomorphism was observed. Imaging in the region of the temporal portion of the original Descemet's defect showed well-defined linear structures with hyper-reflective edges. Compared to 3 years previously, the cornea at the level of Descemet's membrane appeared to have greater reflectivity. This case demonstrates how microstructural changes in the cornea can be described and analysed over time with the assistance of in vivo confocal microscopy.
