Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Macular Degeneration/drug therapy , Meningioma/surgery , Optic Nerve Neoplasms/surgery , Radiosurgery/adverse effects , Tachyphylaxis , Adult , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Bevacizumab , Follow-Up Studies , Humans , Macular Degeneration/diagnosis , Macular Degeneration/etiology , Male , Radiation Injuries/diagnosis , Radiation Injuries/drug therapy , Radiation Injuries/etiology , Ranibizumab , Tomography, Optical CoherenceABSTRACT
OBJECTIVE: To determine the value of optical coherence tomography (OCT) as a diagnostic tool in the critical evaluation of phenotypic variability seen in an aniridia family with a novel PAX6 mutation. DESIGN: Genetic and observational family study. PARTICIPANTS: Three-generation family segregating autosomal dominant aniridia. METHODS: Ophthalmic examination included best-corrected visual acuity, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, tonometry, and OCT. PAX6 gene mutation analysis was carried out by direct sequencing of gene-specific PCR products and protein analysis by Western blot. RESULTS: Intrafamilial variable expressivity was seen between 4 affected family members. Phenotype differences between twin children suggested that this was due to modifier gene effects rather than environment. Anterior segment OCT demonstrated a range of iridocorneal angle abnormalities and corneal thickening in only 3, but ciliary body hypoplasia in all 4 affected patients. Posterior segment OCT demonstrated dome-shaped, hypoplastic macular profiles in the 2 affected children. Novel outer retinal changes were also seen, suggestive of a phototoxic retinopathy not previously recognized in aniridia. Ocular disease segregated with a novel PAX6 Q178X nonsense mutation with Western blot analysis suggesting that this led to haploinsufficiency of PAX6 protein. CONCLUSIONS: Non-contact OCT imaging allowed for a more detailed assessment of anterior and posterior segment disease in children and adults with aniridia plus nystagmus. This led to the identification of novel features and highlights a practical, non-contact strategy well suited to genotype/phenotype studies and the longitudinal management of aniridic glaucoma in children.