Familial normal tension glaucoma genetics.

Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor for developing glaucoma. However, glaucoma can occur at any IOP. Normal tension glaucoma (NTG) arises with IOPs that are within what has been defined as a normal range, i.e., 21 mm Hg or less, which may present challenges in its diagnosis and management. Identifying inheritance patterns and genetic mutations in families with NTG has helped elucidate mechanisms of NTG, however the pathophysiology is complex and not fully understood. Approximately 2% of NTG cases are caused primarily by mutations in single genes, optineurin (OPTN), TANK binding kinase 1 (TKB1), or myocilin (MYOC). Herein, we review pedigree studies of NTG and autosomal dominant NTG caused by OPTN, TBK1, and MYOC mutations. We review identified mutations and resulting clinical features of OPTN-associated and TBK1-associated NTG, including long-term follow up of these patients with NTG. In addition, we report a new four-generation pedigree of NTG caused by a Glu50Lys OPTN mutation, including six family members with a mean follow up of 17 years. Common features of OPTN -associated NTG due to Glu50Lys mutation included early onset of disease with an IOP <21 mm Hg, marked optic disc cupping, and progressive visual field loss which appeared to stabilize once an IOP of less than 10 mm Hg was achieved. Lastly, we review risk factor genes which have been identified to contribute to the complex inheritance of NTG.

Familial juvenile normal-tension glaucoma with anterior segment dysgenesis: a clinical report of a new phenotype.

PURPOSE: To describe a new familial syndrome consisting of anterior segment dysgenesis, glaucomatous optic neuropathy, and intraocular pressure (IOP) in the normal range. DESIGN: Observational case series. METHODS: Subjects were available for examination from a 2-generation pedigree. Ophthalmic examination and photography, visual field examination, and optical coherence tomography of the peripapillary retinal nerve fiber layer were performed. In some subjects, medical work-up was performed. RESULTS: Eight affected subjects were identified. All had signs of Axenfeld-like anterior segment dysgenesis, ranging from a single fine iris process to diffuse broad iris synechiae extending to a prominent posterior embryotoxon. Four of the 8 subjects had glaucoma-appearing optic nerve heads with corresponding visual field defects; in a fifth subject, glaucoma was suspected on the basis of optic nerve appearance, but the visual field was full. IOP was consistently in the low-teens to mid-teens except in 1 eye in which it was 22 mm Hg, the highest recorded pressure in all examined subjects. CONCLUSIONS: A new phenotype is presented, characterized by IOP in the normal range, glaucomatous-appearing optic nerve cupping, and anterior segment dysgenesis. The suggested mode of inheritance is autosomal dominant with marked intrafamilial variability.