Faculty Bibliography

PURPOSE: To compare ultrahigh-resolution optical coherence tomography (UHR-OCT) technology to a standard-resolution OCT instrument for the imaging of macular hole pathology and repair; to identify situations where UHR-OCT provides additional information on disease morphology, pathogenesis, and management; and to use UHR-OCT as a baseline for improving the interpretation of the standard-resolution images. DESIGN: Observational and interventional case series. PARTICIPANTS: Twenty-nine eyes of 24 patients clinically diagnosed with macular hole in at least one eye. METHODS: A UHR-OCT system has been developed and employed in a tertiary-care ophthalmology clinic. Using a femtosecond laser as the low-coherence light source, this new UHR-OCT system can achieve an unprecedented 3-mum axial resolution for retinal OCT imaging. Comparative imaging was performed with UHR-OCT and standard 10-mum resolution OCT in 29 eyes of 24 patients with various stages of macular holes. Imaging was also performed on a subset of the population before and after macular hole surgery. MAIN OUTCOME MEASURES: Ultrahigh- and standard-resolution cross-sectional OCT images of macular hole pathologies. RESULTS: Both UHR-OCT and standard-resolution OCT exhibited comparable performance in differentiating various stages of macular holes. The UHR-OCT provided improved imaging of finer intraretinal structures, such as the external limiting membrane and photoreceptor inner segment (IS) and outer segment (OS), and identification of the anatomy of successful surgical repair. The improved resolution of UHR-OCT enabled imaging of previously unidentified changes in photoreceptor morphology associated with macular hole pathology and postoperative repair. Visualization of the junction between the photoreceptor IS and OS was found to be an important indicator of photoreceptor integrity for both standard-resolution and UHR-OCT images. CONCLUSIONS: Ultrahigh-resolution optical coherence tomography improves the visualization of the macular hole architectural morphology. The increased resolution of UHR-OCT enables the visualization of photoreceptor morphology associated with macular holes. This promises to lead to a better understanding of the pathogenesis of macular holes, the causes of visual loss secondary to macular holes, the timing of surgical repair, and the evaluation of postsurgical outcome. Ultrahigh-resolution optical coherence tomography imaging of macular holes that correspond to known alterations in retinal morphology can be used to interpret retinal morphology in UHR-OCT images. Comparisons of UHR-OCT images with standard-resolution OCT images can establish a baseline for the better interpretation of clinical standard-resolution OCT images. The ability to visualize photoreceptors and their integrity or impairment is an indicator of macular hole progression and surgical outcome.

OBJECTIVE: To introduce the concept of a stage 0 macular hole based on optical coherence tomographic observations of the vitreoretinal interface in fellow eyes of patients with unilateral idiopathic macular holes, and to evaluate the subsequent risk of progression to a full-thickness macular hole. DESIGN: Retrospective observational case series. PARTICIPANTS: Ninety-four patients with a unilateral stage 2, 3, or 4 full-thickness macular hole. METHODS: The medical records of patients with a unilateral macular hole diagnosed between 1994 and 2000 at the New England Eye Center were reviewed. MAIN OUTCOME MEASURE: Development of a full-thickness macular hole in the fellow eye on biomicroscopic fundoscopy or optical coherence tomography (OCT). RESULTS: In 27 (28.7%) of 94 clinically normal fellow eyes, OCT detected an abnormality of the vitreoretinal interface but normal foveal anatomy. The vitreoretinal abnormalities were further subclassified into severe (4 eyes), moderate (8 eyes), and mild (15 eyes) based on the intensity and morphology of the OCT signal. One of the 4 (25%) severe cases progressed to a full-thickness macular hole, 4 of the 8 (50%) moderate cases became full-thickness macular holes, and no (0%) mild cases progressed to a full-thickness macular hole. Severe and moderate eyes seemed to share characteristic features on OCT that increased their risk of macular hole development (stage 0 macular hole). The macular hole-free survival at 48 months was 94% for stage 0-negative patients, versus 54% for stage 0-positive patients. Univariate analysis revealed that the presence of a stage 0 macular hole was significantly associated with an almost 6-fold increase in the risk of macular hole formation (relative risk: 5.8, 95% confidence interval: 1.16-28.61, P = 0.03). CONCLUSIONS: A stage 0 macular hole has a normal biomicroscopic appearance clinically, but has salient features on OCT as a result of oblique vitreous traction. Optical coherence tomographic findings consist of a normal foveal contour and normal retinal thickness and must include the presence of a preretinal, minimally reflective, thin band inserting obliquely on at least one side of the fovea. The presence of a stage 0 macular hole in the fellow eye is a significant risk factor for the development of a second macular hole.

An experimental tracking optical coherence tomography (OCT) system has been clinically tested. The prototype instrument uses a secondary sensing beam and steering mirrors to compensate for eye motion with a closed-loop bandwidth of 1 kHz and tracking accuracy, to within less than the OCT beam diameter. The retinal tracker improved image registration accuracy to <1 transverse pixel (<60 microm). Composite OCT images averaged over multiple scans and visits show a sharp fine structure limited only by transverse pixel size. As the resolution of clinical OCT systems improves, the capability to reproducibly map complex structures in the living eye at high resolution will lead to improved understanding of disease processes and improved sensitivity and specificity of diagnostic procedures.

PURPOSE: A new technique was developed to measure the flow of aqueous humor through the uveoscleral pathway in porcine eyes and to examine whether there is any outflow through the choroid into the vortex veins. METHODS: Enucleated porcine eyes were perfused in vitro under a constant pressure of 10 mm Hg. After total outflow was measured, the episcleral vessels were blocked with cyanoacrylate to eliminate outflow through the conventional pathway. The vortex veins were then blocked, to assess the amount of choroidal drainage. RESULTS: The average outflow in control eyes was found to be 2.8 +/- 0.9 microL/min. After the exit sites of the conventional pathway were blocked, the average outflow decreased to 1.1 +/- 0.5 microL/min. Blocking the vortex veins did not appear to alter uveoscleral outflow further (1.2 +/- 0.8 microL/min). CONCLUSIONS: The results suggest that choroidal drainage into the vortex veins is insignificant in the absence of blood perfusion. No significant washout effects in porcine eyes were observed.

PURPOSE: To investigate the structure-function relationship between optical coherence tomography (OCT) macular retinal and peripapillary nerve fiber layer (NFL) thickness and automated visual field (VF) findings. DESIGN: Cross-sectional observational study. METHODS: Retrospective institutional study where 150 consecutive eyes (101 subjects) from a glaucoma service were included. All the participants had full ophthalmic evaluation, VF testing and prototype OCT scanning at the same visit. Orthogonal OCT macular analysis was obtained to maximize the sampling of the area of interest. Pearson age-adjusted correlation was determined between macular retinal thickness and peripapillary NFL thickness. Area under the receiver operator characteristics (AROC) curves for the association between macular retinal thickness and peripapillary NFL thickness and VF findings were calculated in a subgroup of eyes without VF defect and eyes with VF defect confined to one hemifield. RESULTS: The correlation between macular retinal and peripapillary NFL measurements ranged between r =.27 to.54 for quadrants,.44 to.55 for hemiretina, and.52 for the overall mean. Areas under the receiver operator characteristics for macular thickness were higher in areas corresponding to the VF defect location than the noncorresponding locations. Areas under the receiver operator characteristics for peripapillary NFL thickness were higher than for the macular retinal thickness. Including both macular retinal thickness and peripapillary NFL thickness measurements in the logistic regression model yielded AROCs (range:.69 -.77) similar to those found for the peripapillary NFL alone. CONCLUSION: Macular retinal thickness, as measured by OCT, was capable of detecting glaucomatous damage and corresponded with peripapillary NFL thickness; however, peripapillary NFL thickness had higher sensitivity and specificity for the detection of VF abnormalities.

BACKGROUND AND OBJECTIVE: Comparison of nerve fiber layer (NFL) thickness and macular retinal thickness measurements in two different commercial optical coherence tomography (OCT) machines with the same and different super luminescent diode lasers (SLDs). PATIENTS AND METHODS: Thirty eyes of 30 subjects were studied, with each eye scanned on two different OCT machines on the same day. Three 3.4-mm diameter circumpapillary NFL scans and six 6-mm radial scans centered on the fovea were obtained. Macular volumes were calculated from the central 3.45 mm of the 6 radial scans. RESULTS: The first study (identical SLDs of 850 nm) included 10 eyes of 10 subjects for mean NFL thickness and 6 eyes of 6 subjects for macular volume. There was no systematic difference between the measurements on the two machines for NFL (difference = 5.6 microm, standard error [SE] = 3.8, P= .18) or macular volume (difference = -0.003 mm3, SE = 0.064, P = .96). The second study (SLDs of 850 and 820 nm) included 20 eyes of 20 subjects. There was no significant difference between the two machines for mean NFL (difference = 3.4 microm, SE = 2.9, P= 0.26) or macular volume (difference = -.017 mm3, SE = 0.017, P= .33). For the smaller areas of the macular scan, several (including the outer ring) showed a significant systematic difference between measurements at the two wavelengths, but even these had at most 12% of the total variance attributable to the different wavelengths. CONCLUSION: Our study indicates that OCT measurements of NFL thickness do not differ much when the device or the wavelength of the SLD is changed. Some measurements of the macular thickness in specific areas may differ systematically for different wavelengths, but in most cases the difference is small.

PURPOSE: The measurement reproducibility of the third generation of commercial optical coherence tomography, OCT-3 (StratusOCT, software ver. A2, Carl Zeiss Meditec Inc., Dublin, CA) was investigated. The nerve fiber layer (NFL) thickness, macula thickness map, and optic nerve head (ONH) parameters in normal eyes were studied. METHODS: Ten normal subjects were imaged six times (three before and three after dilation) per day, and the series was repeated on three different days. The order of the scans before pupil dilation was randomized in each of the 3 days of scanning. After pupil dilation, the scans were also randomized in each of the 3 days of scanning. Each series was performed separately for standard-density (128 A-scans per macular and ONH image and 256 A-scans per NFL image) and high-density (512 A-scans per image for all three scan types) scanning. RESULTS: The mean macular thickness was 235 +/- 9.8 micro m. A-scan density (or image acquisition speed) had a statistically significant effect (P < 0.05) on the reproducibility of the mean macular thickness, macular volume, and a few sectors of the macular map. No significant dilation effect was found for any of the macular parameters. The best intraclass correlation coefficient (ICC; 94%) for macular scans was found for dilated high-density scanning, with an intervisit SD of 2.4 micro m and an intravisit SD of 2.2 micro m. The mean NFL thickness for standard scanning was 98 +/- 9 micro m. NFL reproducibility showed mixed results and had interactions between scan density and dilation for some parameters. For most of the NFL parameters, reproducibility was better with dilated standard-density scanning. The mean NFL thickness ICC for dilated standard scanning was 79%, with an intervisit SD of 2.5 micro m and an intravisit SD of 1.6 micro m. For the ONH analysis, the reproducibility was better for dilated standard-density scanning for almost all the parameters, except for disc area, horizontal integrated rim volume, and vertical integrated rim area, which were better before dilation. The best reproducibility was found for cup-to-disc ratio (ICC = 97%, with intervisit SD of 0.04 micro m and intravisit SD of 0.02 micro m). CONCLUSIONS: StratusOCT demonstrated reproducible measurements of NFL thickness, macular thickness, and optic nerve head parameters. The best reproducibility was found for dilated standard scanning for NFL and ONH parameters and for dilated high-density scanning for macular parameters.

Structural assessment using the imaging technologies discussed herein provides reproducible quantitative measurements of posterior segment ocular structures. These measurements have been found to provide useful data for glaucoma detection in various regions of the posterior segment. Further studies are needed to evaluate the utility of these technologies for pre-perimetric glaucoma detection and for monitoring glaucoma progression over an extended period.

Ultrasound biomicroscopy technology has become an indispensable tool in qualitative and quantitative assessment of the anterior segment. Advances in soft-ware design and algorithms will improve theoretical understanding of the pathophysiology of anterior segment disorders. Future applications of quantitative techniques will yield important information regarding mechanisms of angle closure, improving understanding of the dynamic functions of the iris,accommodation, presbyopia, and other aspects of anterior segment physiology and pathophysiology.