Objective: To investigate the temporal relationship between optic nerve head (ONH) surface depression and retinal nerve fiber layer (RNFL) thinning measured by confocal scanning laser ophthalmoscopy (CSLO) and spectral-domain optical coherence tomography (SD-OCT), respectively, during the course of glaucoma progression. Design: Prospective, longitudinal study. Participants: A total of 146 eyes of 90 patients with glaucoma and 70 normal eyes of 35 healthy individuals followed for an average of 5.4 years (range, 48.0-76.6 months). Methods: Eyes were imaged by CSLO (Heidelberg Retinal Tomograph [HRT]; Heidelberg Engineering, GmbH, Dossenheim, Germany) and SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec AG, Dublin, CA) at approximately 4-month intervals for measurement of ONH surface topography and RNFL thickness, respectively. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA) with HRT and Guided Progression Analysis (GPA) with Cirrus HD-OCT, respectively. The survival probabilities were compared with a Cox proportional hazards model. Main Outcome Measures: Number of eyes with progressive ONH and RNFL changes and the sequence of changes. Results: A total of 3238 OCT and 3238 CSLO images obtained in the same follow-up visits were analyzed. At a specificity of 94.3% (4 eyes showed ONH surface depression and 4 eyes showed RNFL thinning in the normal group), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had evidence of both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected before RNFL thinning, with a median lag time of 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival probability of eyes with ONH surface depression was significantly worse than eyes with RNFL thinning (P = 0.002). Conclusions: With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma. A time window for therapeutic intervention may exist on detection of ONH surface depression before there is observable RNFL thinning in glaucoma.

Purpose To evaluate long-term, longitudinal displacement of the optic nerve head (ONH) and anterior lamina cribrosa surfaces in glaucoma patients imaged with spectral-domain optical coherence tomography (SD OCT). Design Prospective study. Participants A total of 173 eyes of 108 subjects (88 with glaucoma and 20 normal subjects) followed for a mean of 5.3 years. Methods The optic disc was imaged with SD OCT at approximately 4-month intervals, and the ONH surface depth (ONHSD), anterior lamina cribrosa surface depth (ALCSD), and prelaminar tissue thickness (PTT) were measured. The reproducibility coefficients of ONHSD, ALCSD, and PTT were calculated from 2 baseline measurements of the glaucoma group. Change in ONHSD/ALCSD/PTT was confirmed when the differences between the first baseline and the latest 2 consecutive follow-up visits were greater than the corresponding reproducibility coefficient. Factors associated with ONHSD and ALCSD changes were identified with linear mixed modeling. Main Outcome Measures Proportion of eyes with ONHSD/ALCSD change. Results Within the glaucoma group, 23.9% (33 eyes) had confirmed ONHSD change (15.2% with posterior and 8.7% with anterior displacement) and 24.6% (34 eyes) had confirmed ALCSD change (12.3% with posterior and 12.3% with anterior displacement). Some 9.4% (13 eyes) showed a decrease in PTT, and 2.2% (3 eyes) showed an increase in PTT. The specificity for detection of ONHSD/ALCSD/PTT change was 91.4% (95% confidence interval [CI], 77.6-97.0), 82.9% (95% CI, 67.3-91.9), and 94.3% (95% CI, 81.4-98.4), respectively. There were no significant differences in the proportion of eyes with visual field progression or history of filtration surgery between the groups with anterior and posterior displacement of ONH/anterior laminar surfaces (P ≥ 0.678). For each millimeter of mercury increase in the average intraocular pressure (IOP) during follow-up, the ONH and anterior laminar surfaces displaced posteriorly by 1.6 μm and 2.0 μm, respectively. An older age was associated with a decrease in magnitude of posterior displacement of the ONH and anterior laminar surfaces (P ≤ 0.009). Conclusions The ONH and anterior laminar surfaces displaced not only posteriorly but also anteriorly (with reference to Bruch's membrane opening) in a significant portion of glaucoma patients. The magnitude of change was related to age and the averaged IOP during follow-up.

Background: The loss of RGCs expressing Thy-1 after optic nerve injury has an initial phase of rapid decline followed by a longer phase with slower reduction rate. This study used longitudinal retinal imaging of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) to determine how the α2-adrenergic agonist brimonidine influences loss of Thy1 promoter activation. Methods. Baseline images of the fluorescent retinal neurons in 30 Thy1-CFP mice were obtained using a modified confocal scanning laser ophthalmoscope. Next, brimonidine (100 ug/kg, IP) was administered either one time immediately after optic nerve crush, or immediately after optic nerve crush and then every 2 days for four weeks. A control group received a single saline injection immediately after optic nerve crush. All animals were imaged weekly for four weeks after optic nerve crush. Loss of fluorescent retinal neurons within specific retinal areas was determined by counting. Results: At one week after optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was 44±7% of baseline in control mice, 51±6% after one brimonidine treatment, and 55±6% after brimonidine treatment every other day (P<0.05 for both brimonidine treatment groups compared to the control group). Subsequently, the number of fluorescent retinal neurons in the group that received one treatment differed insignificantly from the control group. In contrast, the number of fluorescent retinal neurons in the group that received repeated brimonidine treatments was greater than the control group by 28% at two weeks after crush and by 32% at three weeks after crush (P<0.05 at both time points). Rate analysis showed that brimonidine slowed the initial rate of fluorescent cell decline in the animals that received multiple treatments (P<0.05). Differences in the rate of loss among the treatment groups were insignificant after the second week. Conclusion: Repeated brimonidine treatments protect against loss of fluorescence within fluorescent retinal neurons of Thy1-CFP mice after optic nerve crush. As most of fluorescent retinal neurons in this system are RGCs, these findings indicate that repeated brimonidine treatments may protect RGC health following optic nerve crush. © 2013 Dai et al.; licensee BioMed Central Ltd.