Christopher A. Girkin

Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography

OBJECTIVE To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA). DESIGN Prospective instrument validation study. PARTICIPANTS One eye each from 10 normal subjects and 10 glaucoma patients. METHODS Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model. MAIN OUTCOME MEASURES RNFL thickness. RESULTS The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%). CONCLUSION With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.

Radiation Optic Neuropathy after Stereotactic Radiosurgery

PURPOSE The purpose of the study is to report the occurrence of optic neuropathy after stereotactic radiosurgery for perichiasmal tumors. METHODS Records of four patients with visual deterioration after stereotactic radiosurgery were reviewed, including clinical findings, neuroimaging results, and treatment methods. RESULTS Optic neuropathy developed 7 to 30 months after gamma knife radiosurgery. All patients experienced an abrupt change in visual function. Clinical findings indicated anterior visual pathway involvement. Patterns of field loss included nerve fiber bundle and homonymous hemianopic defects. Gadolinium-enhanced magnetic resonance imaging (MRI) showed swelling and enhancement of the affected portion of the visual apparatus in three patients. Systemic corticosteroids were administered in all patients and one partially recovered. One patient also received hyperbaric oxygen without improvement. CONCLUSIONS Although rare, optic neuropathy may follow radiosurgery to lesions near the visual pathways. Careful dose planning guided by MRI with restriction of the maximal dose to the visual pathways to less than 8 Gy will likely reduce the incidence of this complication.

Is there an association between pre-existing sleep apnoea and the development of glaucoma?

Aim: To determine if sleep apnoea is associated with an increased risk of developing glaucoma. Methods: This was a nested case-control study. Patients seen at the Veterans Affairs Medical Center (BVAMC) in Birmingham, Alabama, with newly diagnosed glaucoma (cases) between 1997 through 2001 were selected (n = 667) and age matched with non-glaucomatous controls (n = 6667). Patient information was extracted from the BVAMC data files containing demographic, clinical, and medication information. An index date was assigned to the glaucoma subjects corresponding to the time of diagnosis. Patients who had a glaucoma diagnosis before the observation period of the study were excluded. 10 controls were randomly selected for each case and matched on age (plus or minus 1 year) and an encounter on or before the index date of the matched case. Ihe main outcome measures were crude and adjusted relative risks for the association between the previous diagnosis of sleep apnoea and the development glaucoma. Adjustment was performed for the associations of diabetes, lipid metabolism disorders, hypertension, cardiovascular disease, cerebrovascular disease, arterial disease, and migraines. Results: Individuals who developed glaucoma were more likely to have a previous sleep apnoea diagnosis relative to control subjects. However, this finding was of borderline significance at an alpha of 0.05 (p value = 0.06, odds ratio = 2.20, 95% confidence intervals 0.967 to 5.004). Following adjustment for other potential risk factors, no significant difference was seen (p value = 0.18, odds ratio = 1.80, 95% confidence interval 0.76 to 4.23). Conclusions: This nested case-control study does not support a large impact of sleep apnoea on the eventual development of glaucoma relative to other putative risk factors.

Optical coherence tomography of the retina and optic nerve – a review

Optical coherence tomography (OCT) is a rapid non‐contact method that allows in vivo imaging of the retina, optic nerve head and retinal nerve fibre layer (RNFL). Since its introduction in Ophthalmology approximately a decade ago, the use of this technology has disseminated into the clinical practice. OCT has proven to be a useful ancillary tool for assessing retinal diseases because of its capability to provide cross‐sectional images of the retina, and also to perform quantitative analysis of retinal morphology. In glaucoma, the OCT represents one of the methods capable of documenting and analysing optic disc and RNFL morphology in attempt to diagnose and monitor glaucomatous optic neuropathy. Recently, the spectral domain OCT became available, a new technique that allowed major improvements particularly regarding image acquisition speed and image resolution. Future studies will address how these major technological advances will impact the use of the OCT in research and clinical practice.

The African descent and glaucoma evaluation study (ADAGES): Design and baseline data

OBJECTIVE To identify factors accounting for differences in glaucoma onset and rate of progression between individuals of African descent and European descent. DESIGN A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured. RESULTS Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79). CONCLUSIONS Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group. Trial Registration clinicaltrials.gov Identifier: NCT00221923.

Variation in optic nerve and macular structure with age and race with spectral-domain optical coherence tomography.

PURPOSE To evaluate the effects of age and race on optic disc, retinal nerve fiber layer (RNFL), and macular measurements with spectral-domain optical coherence tomography (SD OCT). DESIGN Cross-sectional observational study. PARTICIPANTS Three hundred fifty adult subjects without ocular disease. METHODS Data from SD OCT imaging of the optic nerve head, peripapillary RNFL, and macula of 632 eyes from 350 subjects without ocular disease were imaged with SD OCT. Multivariate models were used to determine the effect of age and race on quantitative measurements of optic disc, RNFL, and macula. MAIN OUTCOME MEASURES Optic nerve, RNFL, and macular measurements with SD OCT across racial strata and age. RESULTS For optic nerve parameters, participants of European descent had significantly smaller optic disc area than other groups (P<0.0001), and Indian participants had significantly smaller rim area than other groups (P<0.0001). Indian and Hispanic participants had thicker global RNFL measurements than other groups (P<0.0001). Participants of African descent were associated with thinner inner retinal thickness in the macula (P<0.0001). Age was associated with several parameters, with rim area reducing by 0.005 mm(2)/year, RNFL thickness reducing by 0.18 μm/year, and inner retinal thickness reducing by 0.1 μm/year (P<0.0001 for all age associations). CONCLUSIONS Optic nerve, RNFL, and macular measurements with SD OCT all varied across racial groups and with age. These differences are important in defining the range of normal variation in differing populations and should be considered in the use of these instruments in the detection of optic nerve and macular disease across these population groups. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

The Post-Illumination Pupil Response Is Reduced in Glaucoma Patients

PURPOSE The post-illumination pupil response (PIPR), which is driven by the intrinsic response of melanopsin-containing, intrinsically photosensitive retinal ganglion cells, has previously been characterized in healthy eyes. The present study examined whether the PIPR is affected in patients with glaucoma compared with healthy subjects. METHODS Sixteen glaucoma patients (mean age, 63.7 years) were tested by presenting a 60°, 10-second light stimulus (13 log quanta/cm(2)/s retinal irradiance) of either 470 nm (blue) or 623 nm (red) to one eye after dilation. The consensual pupil response of the fellow undilated eye was recorded by infrared pupillometry for 50 seconds after light offset. These pupillary responses were compared with those of 19 age-matched controls (mean age, 59 years). RESULTS The glaucoma patients displayed a net PIPR (blue PIPR minus red PIPR) that was significantly (t-test, P < 0.001) smaller (0.6 mm, SEM 0.12; P < 0.05) than in age-matched controls (1.3 mm, SEM 0.16; P < 0.001). For the patient population, the magnitude of the net PIPR was inversely correlated with the measured visual field loss (mean deviation) of the tested eye. CONCLUSIONS This study demonstrates that there is a significant decrease in the ipRGC-mediated PIPR in glaucomatous patients when compared to age-matched controls. As the severity of the glaucomatous neuropathy increases, there is a correlated decrease in the PIPR. Therefore, this test has the potential for use as a clinical tool in evaluating patients with glaucoma.

Post-illumination Pupil Response in Subjects without Ocular Disease

PURPOSE A sustained pupilloconstriction is often observed after the cessation of a bright visual stimulus. This post-illumination pupil response (PIPR) is produced by the intrinsically photosensitive retinal ganglion cells (ipRGCs). The present study was designed to examine the characteristics of the PIPR in a normal population without ocular disease. METHODS Thirty-seven subjects (mean age, 48.6 years) were tested by presenting a 60 degrees, 10-second light stimulus (13 log quanta/cm(2)/s retinal irradiance) and recording pupillary responses for 50 seconds after light cessation. The light stimuli (470 [blue] and 623 [red] nm) were presented by an optical system to one eye after dilation, while the consensual pupil response of the fellow, undilated eye was recorded by infrared pupillometry. RESULTS A positive PIPR was seen in all subjects tested. The population average of the PIPR for 470-nm light was 1.5 mm (SEM 0.10, P < 0.05) and the net PIPR (blue PIPR minus red PIPR) was 1.4 mm (SEM 0.09, P < 0.0001). The net PIPR correlated positively with baseline pupil diameter (P < 0.05), but not significantly with age, race, or sex (P > 0.05) in the test population. CONCLUSIONS All normal subjects displayed a significant PIPR for a 10-second, 470-nm light stimulus, but not a 623-nm stimulus, which is consistent with the proposed melanopsin-mediated response. In most normal individuals, the amplitude of the PIPR was substantial. This test has the potential to be used as a tool in evaluating subjects with inner retinal dysfunction or melanopsin-related disorders.

African Descent and Glaucoma Evaluation Study (ADAGES): III. Ancestry Differences in Visual Function in Healthy Eyes

OBJECTIVE To investigate differences in visual function between the healthy eyes of people of African (AD) and European descent (ED). METHODS Visual function was assessed in 393 AD and 367 ED participants selected from the African Descent and Glaucoma Evaluation Study and the Diagnostic Innovations in Glaucoma Study. Participants had normal appearance of the optic disc and intraocular pressure of less than 22 mm Hg. Each participant had 2 reliable 24-2 standard automated perimetry tests, and most had short-wavelength automated perimetry and frequency-doubling technology tests. The generalized estimating equation was used to adjust for intereye correlations. Results were adjusted for age, vertical cup-disc ratio, disc size, central corneal thickness, and presence of high blood pressure. RESULTS The AD participants were younger (mean [SD] age, 46.2 [13.2] years) than the ED participants (age, 49.5 [16.6] years) (P = .003). The AD participants had worse mean deviation and pattern standard deviation and more points triggered as abnormal on the total and pattern deviation plots compared with ED participants on all tests (P < .05). A larger percentage of AD participants had confirmed abnormal glaucoma hemifield test results on standard automated perimetry only. CONCLUSIONS People of AD have significantly worse performance than people of ED on all tests of visual function. Additional research using longitudinal data is needed to determine the cause of these small but significant ancestry differences in visual function.

Estimating the Rate of Retinal Ganglion Cell Loss in Glaucoma

PURPOSE To present and evaluate a new method of estimating rates of retinal ganglion cell (RGC) loss in glaucoma by combining structural and functional measurements. DESIGN Observational cohort study. METHODS The study included 213 eyes of 213 glaucoma patients followed up for an average of 4.5 ± 0.8 years with standard automated perimetry visual fields and optical coherence tomography. A control group of 33 eyes of 33 glaucoma patients underwent repeated tests over a short period to test the specificity of the method. An additional group of 52 eyes from 52 healthy subjects followed up for an average of 4.0 ± 0.7 years was used to estimate age-related losses of RGCs. Estimates of RGC counts were obtained from standard automated perimetry and optical coherence tomography, and a weighted average was used to obtain a final estimate of the number of RGCs for each eye. The rate of RGC loss was calculated for each eye using linear regression. Progression was defined by a statistically significant slope faster than the age-expected loss of RGCs. RESULTS From the 213 eyes, 47 (22.1%) showed rates of RGC loss that were faster than the age-expected decline. A larger proportion of glaucomatous eyes showed progression based on rates of RGC loss rather than based on isolated parameters from standard automated perimetry (8.5%) or optical coherence tomography (14.6%; P < .01), while maintaining similar specificities in the stable group. CONCLUSIONS The rate of RGC loss estimated from combining structure and function performed better than either isolated structural or functional measures for detecting progressive glaucomatous damage.