Makoto Aihara

Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy.

PURPOSE To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). DESIGN Observational cohort study. METHODS The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. RESULTS Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). CONCLUSIONS Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.

Episcleral venous pressure of mouse eye and effect of body position

Purpose. To measure the episcleral venous pressure (EVP) of the mouse eye and to investigate the effect of body position on EVP and intraocular pressure (IOP). Methods. A microneedle connected to a pressure transducer was used to measure IOP in NIH Swiss white mice. To measure EVP, a reservoir connected to this transducer allowed modulation of the intracameral pressure by changing its height. As intracameral pressure was gradually lowered, there was an observable reflux of erythrocytes from an episcleral vein into Schlemm’s canal. The IOP at which this occurred was the endpoint of the EVP measurement. EVP and IOP were measured in a horizontal body position (0°) analogous to an awake mouse and at 30° and 60° head-down body position from the horizontal position. EVP was measured twice in each eye of 6 mice. Results. Mean IOP at 0°, 30° and 60° of head-down position was 16.5 ± 0.6, 18.2 ± 0.6, and 19.5 ± 1.8 mmHg, respectively. EVP (horizontal) was 9.6 ± 1.3mmHg (N = 6 eyes). EVP significantly increased with increasing degree of head-down position (SNK test, p < 0.05). EVP at 30° and 60° of head-down position was 11.2 ± 1.3 and 13.3 ± 1.5mmHg, respectively. Conclusions. Mouse EVP was successfully measured based on the detection of erythrocyte reflux from an episcleral vein into Schlemm’s canal. Both EVP and IOP increased with the degree of the head-down body position.

Effect on Diurnal Intraocular Pressure Variation of Eliminating the α-2 Adrenergic Receptor Subtypes in the Mouse

PURPOSE To investigate the effect on circadian variation of intraocular pressure (IOP) of eliminating the alpha2A-, alpha2B-, or the alpha2C-adrenergic receptor subtypes in the mouse. METHODS A microneedle method was used to measure IOP in knockout mice lacking the alpha2A-, alpha2B-, or the alpha2C-receptor (alpha2A-R(-/-), alpha2B-R(-/-), alpha2C-R(-/-)), in wild-type mice of the alpha2B knockout strain (alpha2B-R(+/+)), and in the background strain mice, C57BL/6. All mice were maintained in a 12-hour light-dark cycle commencing at 0600 hours. IOP was measured at 0900 and 2100 hours in the five groups: C57BL/6 (n = 8), alpha2A-R(-/-) (n = 10), alpha2B-R(-/-) (n = 8), alpha2B-R(+/+) (n = 8), and alpha2C-R(-/-) (n = 10). In parallel experiments, eyes from the alpha2A-R(-/-), alpha2B-R(-/-), alpha2C-R(-/-), and C57BL/6 mice were embedded in epoxy resin, and semithin sections were stained with toluidine blue. RESULTS IOP at 0900 hours in B6, alpha2A-R(-/-), alpha2B-R(-/-), alpha2B-R(+/+), and alpha2C-R(-/-) mice was 17.1 +/- 1.8, 17.7 +/- 1.4, 17.1 +/- 2.1, 17.6 +/- 1.3, and 17.3 +/- 0.9 mm Hg, respectively (mean +/- SD). IOP at 2100 hours in the same eyes was 19.6 +/- 1.9, 19.2 +/- 2.2, 20.5 +/- 1.5, 19.7 +/- 0.8, and 21.3 +/- 2.7 mm Hg, respectively. There was no significant difference among these genotypes in IOP measured at either time point (P > 0.05, ANOVA). Within each genotype, IOP at 2100 hours was significantly higher than IOP at 0900 hours (C57BL/6, alpha2B-R(-/-), alpha2B-R(+/+), and alpha2C-R(-/-): P < 0.01; alpha2A-R(-/-): P < 0.05, paired t-test). Differences in the diurnal IOP change among the different genotypes were insignificant (P > 0.05, ANOVA). Histopathologic assessment found minimal differences in the structural organization of the anterior segment among the alpha2A-R(-/-), alpha2B-R(-/-),alpha2C-R(-/-), or C57BL/6 mice. CONCLUSIONS These results indicate that IOP magnitude and circadian variation are minimally altered by the absence of the alpha2A-, alpha2B-, or alpha2C-receptor subtypes in transgenic mice.