Tonography demonstrates reduced facility of outflow of aqueous humor in myocilin mutation carriers.
OBJECTIVE
To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography.


METHODS
Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography.


RESULTS
Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant.


CONCLUSIONS
Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.
Wilkinson
Colleen H
CH
Center for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisbourne Street, East Melbourne, Australia 3002.
van der Straaten
David
D
Craig
Jamie E
JE
Coote
Michael A
MA
McCartney
Paul J
PJ
Stankovich
Jim
J
Stone
Edwin M
EM
Mackey
David A
DA
D001082:Aqueous Humor / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D018450:Disease Progression; D005136:Eye Proteins / Q000235:genetics*; D005901:Glaucoma / Q000235:genetics / Q000503:physiopathology; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000503:physiopathology*; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin