Baseline Fourier-Domain Optical Coherence Tomography Structural Risk Factors for Visual Field Progression in the Advanced Imaging for Glaucoma Study.

PURPOSE: To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. DESIGN: Multicenter cohort study. METHODS: Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. RESULTS: A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. CONCLUSION: Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model.

Is There Any Role for the Choroid in Glaucoma?

The choroid is part of the uveal tract and is a heavily vascularized bed that also contains connective tissue and melanin pigment. Given the role of the choroidal vasculature in the blood supply of the anterior laminar and prelaminar regions of the optic nerve head, the peripapillary choroid might be a relevant target for investigation in patients with glaucoma. The purpose of this paper is to critically review the current understanding of potential role of the choroid in the pathogenesis of glaucomatous damage.

Surgical outcomes of inflammatory glaucoma: a comparison of trabeculectomy and glaucoma-drainage-device implantation.

PURPOSE: Our aim was to compare surgical outcomes of trabeculectomy and nonvalved glaucoma-drainage-device (GDD) implantation in eyes with chronic inflammatory glaucoma and uncontrolled intraocular pressure (IOP). METHODS: A retrospective chart review was conducted on patients with glaucomatous optic neuropathy, chronic anterior or posterior segment inflammation, and ≥6 months postoperative follow-up. All eyes underwent trabeculectomy with either antifibrotic therapy or implantation of a Baerveldt GDD (Abbott Laboratories Inc., Abbott Park, IL, USA). Failure was defined as IOP >21 mmHg, <20 % reduction below baseline or IOP <5 mmHg on two consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light-perception vision. Statistical methods consisted of Student's t tests, χ(2) test, and Kaplan-Meier time to failure analysis. RESULTS: Nineteen trabeculectomies of 42 patients were followed for a mean of 31 ± 23 and 23 GDD eyes for a mean of 39 ± 19 months (P = 0.22). At last follow-up, mean IOP (11.83 ± 4.59 and 13.15 ± 6.11 mmHg, P = 0.45) and number of glaucoma medications (1.28 ± 1.56 and 1.26 ± 1.25, P = 0.97) were similar between the trabeculectomy and GDD groups. The frequency and types of postoperative complications in both groups were similar. The cumulative probability of failure after 5 years of follow-up was significantly greater in trabeculectomy eyes (62 %) compared with GDD eyes (25 %) (P = 0.006). CONCLUSIONS: Nonvalved tube-shunt surgery was more likely to maintain IOP control and avoid reoperation than trabeculectomy with antifibrotic therapy in eyes with chronic inflammatory glaucoma.

Reproducibility of retinal oxygen saturation in normal and treated glaucomatous eyes.

AIM: To measure the reproducibility of retinal oxygen saturation (SaO2) levels among treated glaucomatous eyes and normal controls in a prospective non-randomised study. METHODS: Patients with perimetric glaucoma (PG) and normal controls were included. Exclusion criteria for both groups included visual acuity <20/30, unreliable visual fields, thyroidopathies, hemoglobinopathies, cardiovascular and pulmonary diseases. Retinal oximetry was performed twice consecutively on one randomly selected eye of PG and normal controls using spectrophotometric retinal oximeter (SRO; Oxymap ehf., Iceland). Four main retinal vessel pairs were analysed separately. Coefficients of variability (CoV), coefficients of repeatability (CoR) and intraclass correlation coefficients (ICCs) in arteries (a.SaO2) and veins (v.SaO2) were calculated. RESULTS: 23 PG (mean age 68.3±10.8 years) and 22 normal subjects (mean age 61.5±18.2 years; p=0.14) were included. The intraocular pressure and mean ocular perfusion pressure in glaucoma (14.4±4.2 mm Hg; 45.8±5.8 mm Hg) and controls (14.3±3.3 mm Hg; 45.8±6.1 mm Hg) were similar (p >0.05). In the PG group, the a.SaO2 had a CoV of 1.6%, a CoR of 4.7 and an ICC of 0.97; the v.SaO2 had a CoV of 5.9%, a CoR of 8.7 and an ICC of 0.96. In normals, the a.SaO2 had a CoV of 0.98%, a CoR of 3.3 and an ICC of 0.97; the v.SaO2 had a CoV of 4.8%, a CoR of 7.7 and an ICC of 0.93. CONCLUSIONS: Retinal oximetry measurements using SRO are highly reproducible in both treated glaucomatous and normal eyes.

Short-term enhancement of visual field sensitivity in glaucomatous eyes following surgical intraocular pressure reduction.

PURPOSE: To examine the hypothesis that surgical intraocular pressure (IOP) reduction leads to enhancement of visual field (VF) sensitivity in glaucomatous eyes. DESIGN: Prospective case-control study. METHODS: Patients with uncontrolled IOP requiring trabeculectomy or aqueous drainage device were enrolled. Controls consisted of medically treated glaucoma patients with stable IOP and no change in medical therapy during follow-up. Two baseline preoperative VFs and 3 follow-up VF examinations at 1, 2, and 3 months postoperatively were used for analysis. The same number of VF examinations measured within an 18-month interval was used for control eyes. VF locations with significant change were defined as exceeding 95% test-retest confidence limits based upon the mean sensitivity using the 2 baseline VF exams. The number of significantly changing locations per eye and changes in mean and pattern standard deviation (PSD) from the mean baseline fields were compared between groups using a Poisson generalized estimating equation model. RESULTS: Thirty eyes of 30 surgically treated glaucoma patients and 41 eyes of 28 stable controls were enrolled. Postoperative IOP was decreased at follow-up 3 compared with baseline (P < .001) in the surgical eyes, but was similar in control eyes (P = .92). At follow-up 3, the number of test locations improving in central (P = .014) and peripheral (P = .019) VF locations was significantly greater in the surgical eyes. The number of eyes with improved PSD at follow-up 3 was significantly greater in the surgical eyes compared with controls (P = .02). CONCLUSIONS: Short-term enhancement of central and peripheral VF sensitivity occurs after surgical reduction of IOP in glaucomatous eyes and may represent a potential biomarker for retinal ganglion cell response to therapeutic interventions in glaucoma.

Retinal blood flow in glaucomatous eyes with single-hemifield damage.

PURPOSE: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere. DESIGN: Prospective, nonrandomized, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls. METHODS: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed. MAIN OUTCOME MEASURES: Total and hemispheric RS, RBF, RNFL, and GCC values. RESULTS: The total RBF (34.6±12.2 µl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 µl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 µl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 µm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 µm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 µl/minute), RNFL (103.7 ± 20.6 µm), and GCC (83.6 ± 10.1 µm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 µl/minute, 124.8 ± 9.6 µm, and 96.1 ± 5.7 µm, respectively). CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

The impact of topical mydriatic ophthalmic solutions on retinal vascular reactivity and blood flow.

The impact of mydriatic agents on the standardized provocation of retinal vascular reactivity has not been systematically investigated. Our aim was to investigate the effect of commonly used mydriatic agents on the provoked vascular response of retinal arterioles. One eye was randomly selected for mydriasis from 10 healthy volunteers (age 23.3 ± 4.9 years). A single drop of: 1% tropicamide (T), or a combination of 0.8% tropicamide and 5% phenylephrine (TP), or 1% cyclopentolate (C) were instilled into the volunteers lower fornix at each of three visits. Volunteers underwent a standardized isocapnic hyperoxic provocation. Four retinal hemodynamic measurements were acquired with the Canon Laser Blood Flowmeter at equivalent positions on the superior temporal arteriole (STA) and inferior temporal arteriole (ITA) at baseline, during provocation and after recovery. Statistical analysis was performed using linear mixed-effect models. Pre- and post-dilation measurements indicated that pupil diameter increased with use of T, TP, C (all <0.001), while systolic blood pressure, diastolic blood pressure and intraocular pressure did not change significantly (all >0.05). In response to a standardized isocapnic hyperoxic challenge, blood vessel diameter, blood velocity and flow decreased in both the STA and ITA relative to baseline. Comparison between the change elicited by isocapnic hyperoxic gas stimuli with respect to blood vessel diameter, blood velocity, blood flow, were equivalent for each mydriatic agent in the STA (p = 0.66, p = 0.99, p = 0.99, respectively) and the ITA (p = 0.85, p = 0.80, p = 0.66, respectively). Furthermore, comparison between the change in the STA and ITA with respect to the above parameters showed equivalent responses in both vessels for each mydriatic agent: T (p = 0.92, p = 0.99, p = 0.35; respectively), TP (p = 0.89, p = 0.96, p = 0.62; respectively), and C (p = 0.87, p = 0.35, p = 0.56; respectively). The provoked retinal vascular reactivity response to standardized isocapnic hyperoxia was equivalent irrespective of the agent used to achieve mydriasis.

The impact of surgical intraocular pressure reduction on visual function using various criteria to define visual field progression.

PURPOSE: To examine the impact of surgical intraocular pressure (IOP) reduction on visual function using various methods to define visual field (VF) progression. METHODS: A retrospective chart review was conducted on consecutive glaucoma patients who underwent surgical IOP reduction between January 1, 2002 and December 31, 2007. All subjects had glaucomatous optic neuropathy, a minimum of 5 preoperative and 5 postoperative VFs, and were followed for a minimum of 2 years both before and after surgery. VF progression was determined using guided progression analysis, linear regression analysis of the visual field index, and individual sensitivity values using Progressor software. RESULTS: Seventeen eyes of 17 patients (mean age 77.9±9.9 y) were enrolled. Subjects were followed for a mean 5.8±2.4 years before surgery and 4.5±1.5 years after surgery. The mean postoperative IOP (11.3±4.2 mm Hg) and medications (1.3±1.3) were significantly (P<0.001 and P=0.01) reduced compared with before surgery (18.0±3.9 mm Hg, 2.4±0.9, respectively). The number of eyes judged to have VF progression using any method during the postoperative period (3 of 17, 17.6%) was significantly (P=0.03) reduced compared with the preoperative period (9 of 17 eyes, 52.9%). Using visual field index criteria, 8 eyes were judged to have preoperative VF progression and 1 eye had persistent VF progression during the postoperative period. None of the eyes judged to have preoperative VF progression using Early Manifest Glaucoma Trial (n=4) and Progressor criteria (n=1) demonstrated persistent VF progression during the postoperative period. Among eyes with preoperative VF progression, the postoperative slope of mean deviation (-0.21±0.23 dB/y) was significantly (P=0.03) reduced compared with before surgery (-1.01±0.23 dB/y). CONCLUSIONS: Despite differences in the criteria used to define VF progression, glaucoma surgical IOP reduction significantly reduces the incidence and rate of VF progression.

Glaucoma Diagnosis and Monitoring Using Advanced Imaging Technologies.

Advanced ocular imaging technologies facilitate objective and reproducible quantification of change in glaucoma but at the same time, impose new challenges on scientists and clinicians for separating true structural change from imaging noise. This review examines time-domain and spectral-domain optical coherence tomography, confocal scanning laser ophthalmoscopy and scanning laser polarimetry technologies and discusses the diagnostic accuracy and the ability of each technique for evaluation of glaucomatous progression. A broad review of the current literature reveals that objective assessment of retinal nerve fiber layer, ganglion cell complex and optic nerve head topography may improve glaucoma monitoring when used as a complementary tool in conjunction with the clinical judgment of an expert.

Retinal nerve fiber layer atrophy is associated with visual field loss over time in glaucoma suspect and glaucomatous eyes.

PURPOSE: To compare prospectively detection of progressive retinal nerve fiber layer thickness (RNFL) atrophy identified using time-domain optical coherence tomography with visual field progression using standard automated perimetry in glaucoma suspect and preperimetric glaucoma patients or perimetric glaucoma patients. DESIGN: Prospective, longitudinal clinical trial. METHODS: Eligible eyes with 2 years or more of follow-up underwent time-domain optical coherence tomography and standard automated perimetry every 6 months. The occurrence of visual field progression was defined as the first follow-up visit reaching a significant (P < .05) negative visual field index slope over time. RNFL progression or improvement was defined as a significant negative or positive slope over time, respectively. Specificity was defined as the number of eyes with neither progression nor improvement, divided by the number of eyes without progression. Cox proportional hazard ratios were calculated using univariate and multivariate models with RNFL loss as a time-dependent covariate. RESULTS: Three hundred ten glaucoma suspect and preperimetric glaucoma eyes and 177 perimetric glaucoma eyes were included. Eighty-nine eyes showed visual field progression and 101 eyes showed RNFL progression. The average time to detect visual field progression in those 89 eyes was 35 ± 13 months, and the average time to detect RNFL progression in those 101 eyes was 36 ± 13 months. In multivariate Cox models, average and superior RNFL losses were associated with subsequent visual field index loss in the entire cohort (every 10-µm loss; hazard ratio, 1.38; P = .03; hazard ratio, 1.20; P = .01; respectively). Among the entire cohort of 487 eyes, 42 had significant visual field index improvement and 55 had significant RNFL improvement (specificity, 91.4% and 88.7%, respectively). CONCLUSIONS: Structural progression is associated with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may predict subsequent standard automated perimetry loss.

Retinal oximetry using ultrahigh-resolution optical coherence tomography.

BACKGROUND: The purpose of this study was to investigate the repeatability of retinal oximetry using slit-lamp adapted ultrahigh-resolution optical coherence tomography (SL-UHR-OCT). METHODS: SL-UHR-OCT was developed and fringe patterns were obtained for a major retinal artery and a major retinal vein. A-scans at the central wavelengths of 805 nm and 855 nm were analyzed for calculating optical density ratios (ODRs), from which the percentage oxygen saturation was calculated. Measurements were made on two occasions for each person. Repeatability and coefficients of repeatability were calculated. RESULTS: The mean ODRs of the artery were 0.79 ± 0.86 and 0.88 ± 0.97 in sessions 1 and 2, respectively. The mean ODRs of the vein were -0.08 ± 0.69 and 0.14 ± 0.77 between the two sessions, and were significantly lower than that of the artery (P < 0.05). The coefficients of repeatability were 1.44 and 1.81 for the artery and vein, respectively. The mean oxygen saturation of the major retinal artery was 94% ± 45% and 98% ± 51% in sessions 1 and 2, respectively, and the mean oxygen saturation of the major retinal vein was 48% ± 36% and 60% ± 40% between sessions. CONCLUSION: Optical coherence tomographic oximetry for evaluating retinal oxygen saturation was subject to variation, although the averaged measurements in repeated sessions were matched. Further work on reducing variation will be needed.

Relationship among visual field, blood flow, and neural structure measurements in glaucoma.

PURPOSE: To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. METHODS: Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. RESULTS: Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). CONCLUSIONS: There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

A validated risk calculator to assess risk and rate of visual field progression in treated glaucoma patients.

PURPOSE: The purpose of our study is to develop and validate a model to predict visual field (VF) outcomes in patients with treated glaucoma. METHODS: Data from 587 eyes with treated glaucoma evaluated in a cohort were used to develop two equations to predict VF outcomes, one estimating the risk of progression (%) and another estimating the global rate of VF sensitivity change (decibels [dB]/year). These equations, which included variables associated with VF progression in a multivariable model, then were tested in another cohort (n = 62 eyes) followed for at least 4 years. Agreement, discrimination, and calibration of the model in the validation sample were assessed as main outcome measures. RESULTS: The mean difference between observed and predicted global rates of sensitivity change was 0.13 dB/year (95% confidence interval [CI] = 0.06 to 0.18 dB/year) and the mean difference between observed and predicted final VF mean deviation (MD) values was 0.37 dB (95% CI = 0.00 to 0.75 dB). The predictive model had moderate discriminative ability to estimate VF progression in the independent sample (c-index of 0.78, 95% CI = 0.59 to 0.97). CONCLUSIONS: To our knowledge, this is the first attempt to generate and validate a risk model for patients with treated glaucoma. The prediction model showed moderate accuracy in estimating future VF outcomes in an independent glaucoma population, and may be useful for the objective assessment of risk of progressive VF loss.

Detection of progressive retinal nerve fiber layer thickness loss with optical coherence tomography using 4 criteria for functional progression.

PURPOSE: To compare the rates of retinal nerve fiber layer (RNFL) thickness loss using optical coherence tomography (OCT) in progressing versus nonprogressing eyes using 4 methods to define functional progression. METHODS: Normal and glaucomatous eyes with ≥3 years of follow up were prospectively enrolled. Standard automated perimetry (Swedish Interactive Threshold Algorithm Standard 24-2) and OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, CA) imaging were performed every 6 months in glaucomatous eyes. OCT imaging was performed annually in normal eyes. Functional progression was determined using early manifest glaucoma trial criterion, visual field index (VFI), Progressor software, and the 3-omitting method. RESULTS: Seventy-six eyes (46 glaucoma and 30 normal) of 38 patients were enrolled with a mean follow-up of 43.9 ± 5.02 months (range: 36 to 48 mo). Eleven eyes progressed using Progressor criterion, 5 eyes using VFI, 2 eyes using the 3-omitting method, and 2 eyes using Early Manifest Glaucoma Trial criterion. The annual rate of average RNFL loss (µm/y) was significantly greater (P<0.05) in progressing versus nonprogressing eyes using Progressor (-1.0 ± 1.3 vs. 0.02 ± 1.6), VFI (-2.1 ± 1.1 vs. -0.002 ± 1.4), and the 3-omitting method (-2.2 ± 0.2 vs. -0.1 ± 1.5). Mean rate (µm/y) of average and superior RNFL thickness change was similar (P>0.05) in nonprogressing glaucomatous eyes compared with normal eyes. Using linear mixed-effect models, mean (P<0.001) and peak (P=0.01) intraocular pressure were significantly associated with rate of average RNFL atrophy in glaucomatous eyes. CONCLUSIONS: Despite differences in criteria used to judge functional progression, eyes with standard automated perimetry progression have significantly greater rates of RNFL loss measured using OCT compared with nonprogressing eyes.

Relative magnitude of vascular reactivity in the major arterioles of the retina.

The relative magnitude of vascular reactivity to inhaled gas stimuli in the major retinal arterioles has not been systematically investigated. The purpose of this study was to compare the magnitude of retinal vascular reactivity in response to inhaled gas provocation at equivalent measurement sites in the superior-, and inferior-, temporal retinal arterioles (STA, ITA). One randomly selected eye of each of 17 healthy volunteers (age 24.4 ± 4.7) was prospectively enrolled. Volunteers were connected to a sequential gas delivery circuit and a computer-controlled gas blender (RespirAct™, Thornhill Research Inc., Canada) and underwent an isocapnic hyperoxic challenge i.e. P(ET)O(2) of 500 mm Hg with P(ET)CO(2) maintained at 38 mm Hg during baseline and hyperoxia. Four retinal hemodynamic measurements were acquired using bi-directional laser Doppler velocimetry and simultaneous vessel densitometry (Canon Laser Blood Flowmeter, CLBF-100, Japan) at equivalent positions on the STA and ITA. Statistical analysis was performed using linear mixed-effect models. During the hyperoxic phase, the vessel diameter (STA p=0.004; ITA p=0.003), blood velocity (STA p<0.001; ITA p<0.001) and flow (STA p<0.001; ITA p<0.001) decreased in both the STA and the ITA relative to baseline. The diameter, velocity and flow were equivalent between STA and ITA at baseline and during hyperoxia; and their magnitude of change remained comparable with hyperoxia (p>0.05). The magnitude of retinal arteriolar vascular reactivity in response to isocapnic hyperoxic inhaled gas challenge was not significantly different between the STA and ITA. However, the correlation analysis did not reveal a significant relationship between the percentage changes in diameter, velocity and flow of the STA and ITA and did not demonstrate equal responses from the STA and ITA to gas provocation.

Use of colour Doppler imaging in ocular blood flow research.

The main objective of this report is to encourage consistent quality of testing and reporting within and between centres that use colour Doppler imaging (CDI) for assessment of retrobulbar blood flow. The intention of this review is to standardize methods in CDI assessment that are used widely, but not to exclude other approaches or additional tests that individual laboratories may choose or continue to use.

The impact of retardance pattern variability on nerve fiber layer measurements over time using GDx with variable and enhanced corneal compensation.

PURPOSE: To examine the impact of retardance pattern variability on retinal nerve fiber layer (RNFL) measurements over time using scanning laser polarimetry with variable (GDxVCC) and enhanced corneal compensation (GDxECC; both by Carl Zeiss Meditec, Inc., Dublin, CA). METHODS: Glaucoma suspect and glaucomatous eyes with 4 years of follow-up participating in the Advanced Imaging in Glaucoma Study were prospectively enrolled. All eyes underwent standard automated perimetry (SAP), GDxVCC, and GDxECC imaging every 6 months. SAP progression was determined with point-wise linear regression analysis of SAP sensitivity values. Typical scan score (TSS) values were extracted as a measure of retardance image quality; an atypical retardation pattern (ARP) was defined as TSS < 80. TSS fluctuation over time was measured using three parameters: change in TSS from baseline, absolute difference (maximum minus minimum TSS value), and TSS variance. Linear mixed-effects models that accommodated the association between the two eyes were constructed to evaluate the relationship between change in TSS and RNFL thickness over time. RESULTS: Eighty-six eyes (51 suspected glaucoma, 35 glaucomatous) of 45 patients were enrolled. Twenty (23.3%) eyes demonstrated SAP progression. There was significantly greater fluctuation in TSS over time with GDxVCC compared with GDxECC as measured by absolute difference (18.40 ± 15.35 units vs. 2.50 ± 4.69 units; P < 0.001), TSS variance (59.63 ± 87.27 units vs. 3.82 ± 9.63 units, P < 0.001), and change in TSS from baseline (-0.83 ± 11.2 vs. 0.25 ± 2.9, P = 0.01). The change in TSS over time significantly (P = 0.006) influenced the TSNIT average RNFL thickness when measured by GDxVCC but not by GDxECC. CONCLUSIONS: Longitudinal images obtained with GDxECC have significantly less variability in TSS and retardance patterns and have reduced bias produced by ARP on RNFL progression assessment.

The impact of intraocular pressure reduction on retinal ganglion cell function measured using pattern electroretinogram in eyes receiving latanoprost 0.005% versus placebo.

PURPOSE: To evaluate the impact of intraocular (IOP) reduction on retinal ganglion cell (RGC) function measured using pattern electroretinogram optimized for glaucoma (PERGLA) in glaucoma suspect and glaucomatous eyes receiving latanoprost 0.005% versus placebo. METHODS: This was a prospective, placebo-controlled, double masked, cross-over clinical trial. One randomly selected eye of each subject meeting eligibility criteria was enrolled. At each visit, subjects underwent five diurnal measurements between 8:00 am and 4:00 pm consisting of Goldmann IOP, and PERGLA measurements. A baseline examination was performed following a 4-week washout period, and repeat examination after randomly receiving latanoprost or placebo for 4-weeks. Subjects were then crossed over to receive the alternative therapy for 4 weeks following a second washout period, and underwent repeat examination. Linear mixed-effect models were used for the analysis. RESULTS: Sixty-eight eyes (35 glaucoma, 33 glaucoma suspect) of 68 patients (mean age 67.4 ± 10.6 years) were enrolled. The mean IOP (mmHg) after latanoprost 0.005% therapy (14.9 ± 3.8) was significantly lower than baseline (18.8 ± 4.7, p<0.001) or placebo (18.0 ± 4.3), with a mean reduction of -20 ± 13%. Mean PERGLA amplitude (µV) and phase (π-radian) using latanoprost (0.49 ± 0.22 and 1.71 ± 0.22, respectively) were similar (p > 0.05) to baseline (0.49 ± 0.24 and 1.69 ± 0.19) and placebo (0.50 ± 0.24 and 1.72 ± 0.23). No significant (p > 0.05) diurnal variation in PERGLA amplitude was observed at baseline, or using latanoprost or placebo. Treatment with latanoprost, time of day, and IOP were not significantly (p > 0.05) associated with PERGLA amplitude or phase. CONCLUSION: Twenty percent IOP reduction using latanoprost monotherapy is not associated with improvement in RGC function measured with PERGLA.

Quantification of change in axonal birefringence following surgical reduction in intraocular pressure.

BACKGROUND AND OBJECTIVE: the purpose of this study was to examine the hypothesis that retinal nerve fiber layer (RNFL) birefringence increases following surgical reduction of intraocular pressure (IOP). PATIENTS AND METHODS: twenty-six glaucomatous eyes requiring trabeculectomy or drainage implant were enrolled. Optical coherence tomography (OCT), scanning laser polarimetry (SLP), and IOP measurements were performed preoperatively and 3 months postoperatively. The OCT and SLP images were aligned using a new algorithm that aligns the vessels in an OCT image to those in the corresponding SLP reflectance image. The SLP retardance values at the location of the OCT scan circle were then extracted using the OCT scan circle position inferred by the algorithm. Sixty-four corresponding RNFL segments were extracted from SLP and OCT to calculate RNFL birefringence. A significant birefringence change was defined as 1.96 times the weighted test-retest standard deviation in four contiguous segments. RESULTS: preoperative IOP (19.3 ± 6.1 mm Hg) was significantly (P < .001) lower than postoperative IOP (10.4 ± 3.7 mm Hg). Average birefringence magnitude did not change (P = .19) postoperatively. Localized birefringence magnitude increased significantly in 6 (23%) eyes and decreased significantly in 7 (27%) eyes. CONCLUSION: in this cohort, variable changes in localized birefringence were observed following surgical reduction of IOP.