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    Review of: Long-Term Follow-Up of Normal Tension Glaucoma Patients With TBK1 Gene Mutations in One Large Pedigree

    Quist T, Johnson C, Robin A, et al. American Journal of Ophthalmology, June 2020

    This study is the first to report the clinical features of glaucoma associated with a TANK binding kinase (TBK1) gene duplication.

    Study design

    In this retrospective, observational case series, researchers assessed 7 members (14 eyes) of a pedigree with a TBK1 gene duplication. Clinical features such as IOP, central corneal thickness (CCT), optic nerve head appearance and Humphrey visual field findings were followed from diagnosis to the latest follow-up (March 1985–May 2018).


    Mean age at time of diagnosis was 35 (range 22–46 years), with an IOP of 21 mm Hg or less at presentation and throughout follow-up; the average initial IOP was 16 mm Hg. The average CCT was 506 μm (range 463–541 μm) and the average cup-to-disc ratio was 0.9 (range 0.8–0.99). At the initial visit, 1 eye met the criteria for legal blindness. The first visual field mean deviation was, on average, -9.0, with 29% of eyes having no field defects, 29% with early field defects and 43% with severe field defects.

    Topical medication, laser trabeculoplasty and/or trabeculectomy led to a mean 28% IOP reduction in 3 eyes. None of the family members had fast progression (>1 dB/year). Four eyes (33%) had stable visual fields with a 22% reduction in IOP. Three eyes (25%) had slow progression (<0.5 dB/year) with a 45% IOP reduction. Two of these eyes progressed despite having an IOP of 10 mm Hg or less. Five eyes (42%) progressed at a moderate rate (0.5–1 dB/year) and demonstrated a 30.5% IOP reduction; 3 of these eyes received trabeculectomies.


    This study is limited by its small sample size and gaps in follow-up visits.

    Clinical significance

    This study presents a few clinical points. Physicians must be more cautious and observant when managing young patients with glaucoma. Despite slow progression in this subgroup, this progression can become clinically significant when following a young patient over decades. Genetic mutations and family history must also be considered in this patient population. Finally, based on stabilized disease in 1 case in which IOP reduced to 10 mm Hg or less, lower IOP may slow disease progression.