Familial normal tension glaucoma genetics.

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Glaucoma, a leading cause of irreversible blindness, involves optic nerve damage and visual field loss.
• Elevated intraocular pressure (IOP) is a key risk factor, but Normal Tension Glaucoma (NTG) occurs with normal IOP (<21 mm Hg), posing diagnostic challenges.
• The complex pathophysiology of NTG is being elucidated through genetic studies, with ~2% of cases linked to mutations in OPTN, TBK1, or MYOC.

Purpose of the Study:

• To review pedigree studies of NTG and autosomal dominant NTG linked to OPTN, TBK1, and MYOC mutations.
• To summarize identified mutations, clinical features, and long-term follow-up data for OPTN- and TBK1-associated NTG.
• To report a new pedigree demonstrating NTG inheritance due to a Glu50Lys OPTN mutation.

Main Methods:

• Review of existing pedigree studies on NTG and associated genetic mutations.
• Analysis of clinical features and long-term patient follow-up data for specific mutations.
• Presentation of a novel four-generation pedigree with a Glu50Lys OPTN mutation.

Main Results:

• Common features of OPTN-associated NTG (Glu50Lys mutation) include early onset, IOP <21 mm Hg, optic disc cupping, and progressive visual field loss.
• Visual field loss stabilization was observed when IOP was reduced to <10 mm Hg in patients with the Glu50Lys OPTN mutation.
• Identified mutations and clinical outcomes for OPTN- and TBK1-associated NTG are reviewed.

Conclusions:

• Genetic mutations, particularly in OPTN, play a significant role in the pathophysiology of NTG.
• The Glu50Lys OPTN mutation is associated with early-onset NTG, characteristic optic nerve damage, and visual field defects.
• Further research into genetic risk factors is crucial for understanding the complex inheritance of NTG.