TY - JOUR
T1 - Long-Term Follow-up of Normal Tension Glaucoma Patients With TBK1 Gene Mutations in One Large Pedigree
AU - Quist, Tyler S.
AU - Johnson, Chris A.
AU - Robin, Alan L.
AU - Fingert, John H.
N1 - Funding Information:
Other Acknowledgments: The authors gratefully acknowledge the patients that participated in this research project and the expert technical assistance provided by Teresa Kopel, Research Project Coordinator from the University of Iowa, Iowa City, IA.
Funding Information:
Funding/Support: This research was funded in part by the National Eye Institute (NIH R01EY023512 ), Research to Prevent Blindness , and the Hadley-Carver Chair in Glaucoma. Financial Disclosures: Tyler S. Quist has no financial disclosures. Chris A. Johnson is a consultant for Haag-Streit, Centervue, and M & S Technologies. Alan L. Robin is a consultant for Versant Health; has received financial support from the National Institutes of Health and Glaucoma Research Foundation; has received honoraria from Aerie Pharmaceuticals, Inc; is an advisory board member for Aravind Eye Foundation; and is the Executive Vice President of the American Glaucoma Society. John H. Fingert received research support from the National Institutes of Health, The Glaucoma Foundation, and Regeneron Genetics Center and is a consultant for Perfuse Therapeutics. All authors attest that they meet the current ICMJE criteria for authorship.
Funding Information:
Funding/Support: This research was funded in part by the National Eye Institute (NIH R01EY023512), Research to Prevent Blindness, and the Hadley-Carver Chair in Glaucoma. Financial Disclosures: Tyler S. Quist has no financial disclosures. Chris A. Johnson is a consultant for Haag-Streit, Centervue, and M & S Technologies. Alan L. Robin is a consultant for Versant Health; has received financial support from the National Institutes of Health and Glaucoma Research Foundation; has received honoraria from Aerie Pharmaceuticals, Inc; is an advisory board member for Aravind Eye Foundation; and is the Executive Vice President of the American Glaucoma Society. John H. Fingert received research support from the National Institutes of Health, The Glaucoma Foundation, and Regeneron Genetics Center and is a consultant for Perfuse Therapeutics. All authors attest that they meet the current ICMJE criteria for authorship. Other Acknowledgments: The authors gratefully acknowledge the patients that participated in this research project and the expert technical assistance provided by Teresa Kopel, Research Project Coordinator from the University of Iowa, Iowa City, IA.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Purpose: To characterize features of glaucoma associated with a TANK binding kinase 1 (TBK1) gene duplication, which is among the most common molecularly defined causes of normal tension glaucoma (NTG). Design: Retrospective observational case series. Methods: We conducted a retrospective case series, by reviewing medical records of 7 members of a pedigree with NTG caused by TBK1 gene duplications. Clinical features of these patients at diagnosis, throughout management, and at latest follow-up were identified, including age, intraocular pressure (IOP), central corneal thickness (CCT), optic nerve head appearance, and mean deviation (MD) assessed with Humphrey visual field (HVF) testing protocols. Results: At initial diagnosis, the mean age was 35 ± 7 years, IOP was 16 ± 2.1 mm Hg, cup-to-disc (C/D) ratio was 0.9 ± 0.08, and MD assessed via HVF 30-2 and/or 24-2 testing protocols was −9.0 ± 8.9 (range: −1.8 to −27) dB in the 14 study eyes. At initial diagnosis, 4 of 14 eyes (28%) had no visual field defect, 4 (28%) had early visual field defects, and 6 (43%) had severe visual field defects. Patients had a mean follow-up of 21.5 ± 9.0 years and experienced an average reduction of IOP by 28%. Four of 12 eyes (33%) had stable visual fields throughout follow-up, while 8 eyes (67%) had slow-to-moderate progression. The 30-2 and/or 24-2 HVF tests had an average change in MD of −0.53 ± 0.26 dB/year. No eyes had rapid progression with an MD >1.0 dB/year. At final follow-up, the mean IOP was 11.5 ± 2.9, and C/D ratio was 0.94 ± 0.4. At final follow-up, 3 of 14 eyes (21%) had early visual field defects, 4 (29%) had moderate visual field defects, and 7 (50%) had severe visual field defects. Six of 14 eyes (43%) met criteria for legal blindness. Conclusions: We provide the first report of the clinical features and long-term clinical course in a family of NTG patients with TBK1 gene duplications. TBK1-associated glaucoma exhibits classic features of NTG. Patients present with severe disease at a relatively early age and most (67%) have slow-to-moderate progression of their visual field defects. The rate of visual field change appears correlated with the magnitude of IOP, suggesting that it may be advantageous to set extremely low IOP targets for some patients with TBK1-associated glaucoma.
AB - Purpose: To characterize features of glaucoma associated with a TANK binding kinase 1 (TBK1) gene duplication, which is among the most common molecularly defined causes of normal tension glaucoma (NTG). Design: Retrospective observational case series. Methods: We conducted a retrospective case series, by reviewing medical records of 7 members of a pedigree with NTG caused by TBK1 gene duplications. Clinical features of these patients at diagnosis, throughout management, and at latest follow-up were identified, including age, intraocular pressure (IOP), central corneal thickness (CCT), optic nerve head appearance, and mean deviation (MD) assessed with Humphrey visual field (HVF) testing protocols. Results: At initial diagnosis, the mean age was 35 ± 7 years, IOP was 16 ± 2.1 mm Hg, cup-to-disc (C/D) ratio was 0.9 ± 0.08, and MD assessed via HVF 30-2 and/or 24-2 testing protocols was −9.0 ± 8.9 (range: −1.8 to −27) dB in the 14 study eyes. At initial diagnosis, 4 of 14 eyes (28%) had no visual field defect, 4 (28%) had early visual field defects, and 6 (43%) had severe visual field defects. Patients had a mean follow-up of 21.5 ± 9.0 years and experienced an average reduction of IOP by 28%. Four of 12 eyes (33%) had stable visual fields throughout follow-up, while 8 eyes (67%) had slow-to-moderate progression. The 30-2 and/or 24-2 HVF tests had an average change in MD of −0.53 ± 0.26 dB/year. No eyes had rapid progression with an MD >1.0 dB/year. At final follow-up, the mean IOP was 11.5 ± 2.9, and C/D ratio was 0.94 ± 0.4. At final follow-up, 3 of 14 eyes (21%) had early visual field defects, 4 (29%) had moderate visual field defects, and 7 (50%) had severe visual field defects. Six of 14 eyes (43%) met criteria for legal blindness. Conclusions: We provide the first report of the clinical features and long-term clinical course in a family of NTG patients with TBK1 gene duplications. TBK1-associated glaucoma exhibits classic features of NTG. Patients present with severe disease at a relatively early age and most (67%) have slow-to-moderate progression of their visual field defects. The rate of visual field change appears correlated with the magnitude of IOP, suggesting that it may be advantageous to set extremely low IOP targets for some patients with TBK1-associated glaucoma.
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U2 - 10.1016/j.ajo.2020.01.017
DO - 10.1016/j.ajo.2020.01.017
M3 - Article
C2 - 31987900
AN - SCOPUS:85082702324
SN - 0002-9394
VL - 214
SP - 52
EP - 62
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -