Optical coherence tomography angiography of the peripapillary retina and optic nerve head in dominant optic atrophy.

Peripapillar and nerve head vessel density (VD) was measured in 10 patients affected by Dominant optic atrophy (DOA) using optical coherence tomography angiography (OCT-A) and compared to the measurements of 15 age- and gender-matched controls. DOA patients showed VD reduction, mostly in the temporal and inferotemporal peripapillary sectors, according to the preferential involvement of the papillomacular bundle. Despite poor best-corrected visual acuity (BCVA), OCT-A revealed good repeatability. VD correlated with functional (mean deviation of visual field and BCVA) and structural (retinal nerve fiber layer thickness) parameters and could be a non-invasive, quantitative tool for the monitoring of the disease and of the therapeutic approaches.

Evaluation of Retinal Nerve Fiber Layer Thickness and Ganglion Cell Complex Progression Rates in Healthy, Ocular Hypertensive, and Glaucoma Eyes With the Avanti RTVue-XR Optical Coherence Tomograph Based on 5-Year Follow-up.

PURPOSE: To determine retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex (GCC) progression rates for healthy eyes and undertreatment ocular hypertensive (OHT) and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography. MATERIALS AND METHODS: Seventeen healthy subjects (34 eyes), 17 medically treated OHT patients (34 eyes), and 67 medically treated glaucoma patients (122 eyes) were imaged prospectively at 6-month intervals (median follow-up 5.3 y, 11 visits). RESULTS: A minimal negative correlation between baseline RNFLT and RNFLT progression was found in the glaucoma group (r=-0.1708, P=0.0493). In the other groups no correlation between baseline RNFLT or GCC and RNFLT or GCC progression was found, respectively. The mean±SD of the rate of change was -0.33±0.51, -0.44±0.62, and -0.69±0.93 µm/y for average RNFLT, and -0.53±0.36, -0.54±0.52, and -0.80±0.78 for average GCC, for the normal, OHT, and glaucoma eyes, respectively (P>0.05 for all between-group comparisons). In the normal group the highest progression rate was -1.52 µm/y for average RNFLT and -1.28 µm/y for average GCC. Despite maximal medical treatment, progression in the glaucoma group exceeded the highest progression rate of the normal group in 18 eyes (14.8%) for average RNFLT and 24 eyes (19.7%) for average GCC. CONCLUSIONS: We determined progression rates for untreated healthy and under treatment OHT and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography. We found that an average RNFLT progression rate faster than -1.5 µm/y, and an average GCC progression rate faster than -1.3 µm/y are strongly suggestive for uncontrolled glaucomatous progression. Detection of uncontrolled structural progression with trend analysis may assist the early detection of fast progressors.

Improving Accuracy of Grading and Referral of Diabetic Macular Edema Using Location and Extent of Hard Exudates in Retinal Photography.

BACKGROUND: Hard exudates (HE) are used as a surrogate marker for sight-threatening diabetic macular edema (DME) in most telemedicine-based screening programs in the world. This study investigates whether proximity of HE to the center of the macula, and extent of HE are associated with greater clinically significant macular edema (CSME) severity. A novel method for associating optical coherence tomography (OCT) scans with CSME was developed. METHODS: Eligible subjects were recruited from a DRS program in a community clinic in Oakland, California. Ocular fundus of each subject was imaged using 3-field 45-degree digital retinal photography and scanned using central 7-line spectral domain OCT. Two certified graders separated subjects into 2 groups, those with and without HE within 500 microns from the center of the macula. A modified DME severity scale, developed from Early Treatment Diabetic Retinopathy Study data and adapted to OCT thickness measurements, was used to stratify CSME into severe and nonsevere levels for all subjects. RESULTS: The probabilities of severe CSME in groups 1 and 2 were 14.4% (95% CI: 8.2%-23.8%) and 9% (95% CI: 2.4%-25.5%), respectively (P = .556). In post hoc analysis, increase in the number of sectors affected by HE within the central zone of the macula was associated with the increase in the probability of being diagnosed with severe CSME. CONCLUSION: We have proposed OCT-based classification of DME into severe and nonsevere CSME. Based on this limited analysis, severity of CSME is related more to extent of HE rather than proximity to the center of the macula.

RETINAL VASCULAR PERFUSION DENSITY MAPPING USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN NORMALS AND DIABETIC RETINOPATHY PATIENTS.

PURPOSE: To describe a new method of retinal vascular perfusion density mapping using optical coherence tomography angiography and to compare current staging of diabetic retinopathy based on clinical features with a new grading scale based on perifoveal perfusion densities. METHODS: A retrospective review was performed on subjects with diabetic retinopathy and age-matched controls imaged with a spectral domain optical coherence tomography system (Optovue XR Avanti, Fremont, CA). Split-spectrum amplitude-decorrelation angiography (SSADA) generated optical coherence tomography angiograms of the superficial retinal capillaries, deep retinal capillaries, and choriocapillaris. Skeletonized optical coherence tomography angiograms were used to create color-coded perfusion maps and capillary perfusion density values for each image. Capillary perfusion density values were compared with clinical staging, and groups were compared using analysis of variance and Kruskal-Wallis analyses. RESULTS: Twenty-one control and 56 diabetic retinopathy eyes were imaged. Diabetic eyes were grouped according to clinical stage. Capillary perfusion density values from each microvascular layer were compared across all groups. Capillary perfusion density values were significantly lower in nearly all layers of all study groups compared with controls. Trend analysis showed a significant decrease in capillary perfusion density values as retinopathy progresses for most layers. CONCLUSION: Quantitative retinal vascular perfusion density mapping agreed closely with grading based on clinical features and may offer an objective method for monitoring disease progression in diabetic retinopathy.

Choroid thickness measurement with RTVue optical coherence tomography in emmetropic eyes, mildly myopic eyes, and highly myopic eyes.

PURPOSE: To evaluate choroid thickness (CT) with RTVue spectral domain optical coherence tomography (SD-OCT) and the effect of age and myopia in eyes without posterior complications.
 METHODS: In this multicenter cross-sectional study, all enrolled patients were over age 18 and divided them in 3 groups based on refraction: emmetropia (+1 D to -1 D), mild myopia (-1 D to -6 D), and high myopia (-6 D to -20 D) groups. Horizontal scans through the fovea were acquired with RTVue OCT (Optovue Inc., Fremont, California, USA). Choroid thickness was measured at 500 µm intervals up to 1,500 µm temporal and nasal to the fovea by 2 graders. Mean CT was calculated based on the average of the 7 locations. Statistical analysis was performed to evaluate CT at each location, the effects of age and myopia, and grader agreement. 
 RESULTS: A total 85 eyes of 85 subjects (30 emmetropic, 24 myopic, and 31 high myopic) were enrolled. Excellent grader agreement was observed with an intraclass correlation coefficient (ICC) >0.97. The mean CT was 248.2±78.5 (µm) for emmetropia (age = 58±18), 247.0±85.4 (µm) for myopia (age = 45±20), and 131.5±70.9 (µm) for high myopia (age = 54±13). The mean CT was not significantly different between emmetropia and myopia groups, which were significantly thicker than high myopia group. The overall slope of age-related change for the mean CT was -1.95 µm/y and the effect of age differed among the groups. CONCLUSIONS: Choroid thickness can be measured from RTVue OCT images with good reproducibility. Age and high myopia appear to negatively affect CT. The age effect may vary with refraction groups.

Enhanced imaging algorithm for scanning laser polarimetry with variable corneal compensation.

PURPOSE: To describe and investigate a method of improving assessment of retinal nerve fiber layer (RNFL) morphology with scanning laser polarimetry (SLP) with variable corneal compensation (VCC). METHODS: By neutralizing anterior segment birefringence with a variable compensator, the current VCC method allows direct measurement of RNFL retardation. In the new method, enhanced corneal compensation (ECC), the variable compensator was set to introduce a "bias" birefringence. This bias was removed mathematically for each individual pixel to produce the RNFL image. In 177 eyes of healthy subjects, patients with glaucoma, and subjects with ocular hypertension, retardation images were obtained with both VCC and ECC. RESULTS: In the tested eyes, images obtained with ECC showed the expected RNFL appearance better than those obtained with VCC. In addition, the typical scan score, which quantifies the amount of atypia, was higher with ECC than with VCC. The amount of residual anterior segment birefringence dropped significantly with ECC in the various groups. Measurements of peripapillary RNFL retardation showed reduced temporal and nasal values with ECC, whereas superior and inferior values were not significantly different between VCC and ECC. The dynamic range appeared to have increased with ECC. The accuracy of the TSNIT (temporal, superior, nasal, inferior, temporal) average and inferior average for detecting glaucoma was higher with ECC than with VCC. CONCLUSIONS: RNFL morphology may be better assessed with the presented ECC method than with standard VCC. ECC may be implemented in the current VCC systems by means of a software upgrade. It may enhance the clinical utility of the GDx VCC in glaucoma management.

Modeling of scanning laser polarimetry images of the human retina for progression detection of glaucoma.

The development of methods to detect slowly progressing diseases is often hampered by the time-consuming acquisition of a sufficiently large data set. In this paper, a method is presented to model the change in images acquired by scanning laser polarimetry, for the detection of glaucomatous progression. The model is based on image series of 23 healthy eyes and incorporates colored noise, incomplete cornea compensation and masking by the retinal blood vessels. Additionally, two methods for detecting progression, taking either one or two follow-up visits into account, are discussed and tested on these simulated images. Both methods are based on Student's t-tests, morphological operations and anisotropic filtering. The images simulated by the model are visually pleasing, show corresponding statistical properties to the real images and are used to optimize the detection methods. The results show that detecting progression based on two follow-up visits greatly improves the sensitivity without adversely affecting the specificity.

Effect of individualized compensation for anterior segment birefringence on retinal nerve fiber layer assessments as determined by scanning laser polarimetry.

PURPOSE: Scanning laser polarimetry estimates retinal nerve fiber layer (RNFL) thickness through measurement of retardation of a polarized laser light passing through the naturally birefringent RNFL and cornea. The commercial instrument, the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies, Inc., San Diego, CA), uses an anterior segment compensator of fixed magnitude and slow polarization axis to eliminate the contribution of the cornea to the total signal. Previous studies have shown up to 30% of patients are not adequately compensated by this method. The aim of this study was to determine the effect of individualized anterior segment compensation using a newly designed variable compensator on estimates of retinal nerve fiber layer thickness compared with those as determined with the fixed compensator in the commercial device. DESIGN: Comparative, observational case series. PARTICIPANTS: Twenty-eight eyes from 14 normal participants and 24 eyes from 12 patients with bilateral glaucoma. METHODS: Using information derived from a scan of the macula, a newly designed variable anterior segment compensator for the GDx was set to neutralize anterior segment birefringence. Normal participants and patients with glaucoma underwent RNFL measurements using the standard (fixed) compensator and the variable compensator. The results were compared using Hotelling's generalized means test and Bonferroni's adjustment for multiple comparisons. MAIN OUTCOME MEASURES: Standard GDx modulation and thickness parameters as determined with the fixed and variable compensators. RESULTS: All thickness values were statistically significantly lower as determined with the variable compensator, with no discernible differences in any of the modulation parameters. CONCLUSIONS: Individualized anterior segment compensation lowers the RNFL thickness values as determined by scanning laser polarimetry compared with those determined with the standard fixed compensator. This may narrow the normal range and increase the discriminating ability of scanning laser polarimetry between normal and disease. However, modulation is less affected, and the modulation parameters may thus prove more useful for distinguishing between normal and glaucoma.

Three-dimensional imaging of the human retina by high-speed optical coherence tomography.

Conventional optical coherence tomography is based on A-scans, i.e., the fast scan direction is the z-direction. While this technique has been successfully demonstrated for two-dimensional cross sectional imaging of various tissues, it is rather slow if three-dimensional information is to be obtained. We report on a new technique that combines the transverse scanning approach of a confocal scanning laser ophthalmoscope with the depth sectioning capability of OCT. A stable high-frequency carrier is generated by use of an acousto optic modulator, and high frame rate is obtained by using a resonant scanning mirror for the priority scan (x-direction). Our prototype instrument records 64 transverse images consisting of 256x128 pixels in 1.2 seconds, thus providing the fastest retinal 3D OCT scanning system reported so far. We demonstrate the capabilities of our system by measuring and imaging the fovea and the optic nerve head region of healthy human volunteers in vivo.

Individualized compensation of anterior segment birefringence during scanning laser polarimetry.

PURPOSE: To describe a method for assessment and individualized compensation of anterior segment birefringence with scanning laser polarimetry. METHODS: A scanning laser polarimeter (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies, Inc., San Diego, CA) was modified to accommodate a variable compensator. The magnitude and axis of anterior segment birefringence of normal eyes were determined from a polarimetry image of the Henle fiber layer. The variable compensator was then adjusted to minimize anterior segment birefringence. Retinal nerve fiber layer (RNFL) and macular measurements were then obtained. Macular images with individualized compensation served to verify the effectiveness of the compensation. To demonstrate individualized compensation, two sets of three images each were obtained from four eyes of four normal subjects. One set was obtained with individualized compensation and another with fixed compensation, as used in the commercial polarimetry system. RESULTS: In the tested eyes, the magnitude of anterior segment birefringence ranged from 21.7 to 86.3 nm, and the slow axis ranged from 5.7 degrees nasally upward to 54.3 degrees nasally downward. The maximum residual retardation resulting from compensation was 70 nm for fixed compensation and 11.5 nm for individualized compensation. The compensation residual directly affected the assessment of the RNFL by scanning laser polarimetry. RNFL images obtained with individualized compensation were more consistent with the expected anatomy of the eye. In the eyes measured, the range of RNFL thicknesses appeared to be narrower with the variable corneal and lens compensator (VCC) compared with the fixed corneal compensator (FCC). CONCLUSIONS: In eyes with a normal macula, the magnitude and axis of anterior segment birefringence can be determined from a polarimetry image of the Henle fiber layer. Individualized anterior segment compensation can be achieved with the described method so that the measured birefringence largely reflects the RNFL birefringence. Whether and how macular diseases affect this method remain to be investigated.