Faculty Bibliography

PURPOSE: To assess photoreceptor integrity in patients with retinitis pigmentosa (RP) and related diseases using ultra-high resolution optical coherence tomography (UHR-OCT) and to correlate foveal photoreceptor loss with visual acuity. DESIGN: Observational case series. METHODS: Nine eyes of nine patients with RP and related diseases were imaged with UHR-OCT at the ophthalmology clinic. Patients were diagnosed based on history, examination, fluorescein angiography, and electroretinography. Concurrently, 36 eyes of 36 normal subjects were imaged with UHR-OCT. Central foveal thickness (CFT) and foveal outer segment/pigment epithelium thickness (FOSPET) were defined and measured on UHR-OCT images in all subjects and were compared between the two groups using unpaired t tests. The two thickness measurements in RP patients were correlated with visual acuity using Pearson correlation and linear regression. RESULTS: UHR-OCT demonstrated macular photoreceptor thinning in all RP patients. The difference in CFT between RP patients and normal subjects was not statistically significant (P = .103), but the difference in FOSPET between the two groups was significant (P = .003). Visual acuity showed a fair correlation with CFT (Pearson r = -0.43, r(2) = 0.187, P = .245) and an excellent correlation with FOSPET (Pearson r = -0.942, r(2) = 0.887, P < .0001). CONCLUSIONS: In the current study using UHR-OCT, a new thickness measurement termed FOSPET is demonstrated to quantify photoreceptor loss. FOSPET was statistically thinner in patients with RP and related diseases than in normal eyes and showed correlation with logMAR visual acuity. FOSPET appears to be a probable predictor of visual acuity in RP.

PURPOSE: To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models. METHODS: A high-speed, ultrahigh-resolution OCT system using spectral, or Fourier domain, detection has been developed for small animal retinal imaging. Imaging is performed with a contact lens and postobjective scanning. An axial image resolution of 2.8 mum is achieved with a spectrally broadband superluminescent diode light source with a bandwidth of approximately 150 nm at approximately 900-nm center wavelength. Imaging can be performed at 24,000 axial scans per second, which is approximately 100 times faster than previous ultrahigh-resolution OCT systems. High-definition and three-dimensional retinal imaging is performed in vivo in mouse and rat models. RESULTS: High-speed, ultrahigh-resolution OCT enabled high-definition, high transverse pixel density imaging of the murine retina and visualization of all major intraretinal layers. Raster scan protocols enabled three-dimensional volumetric imagingand comprehensive retinal segmentation algorithms allowed measurement of retinal layers. An OCT fundus image, akin to a fundus photograph was generated by axial summation of three-dimensional OCT data, thus enabling precise registration of OCT measurements to retinal fundus features. CONCLUSIONS: High-speed, ultrahigh-resolution OCT enables imaging of retinal architectural morphology in small animal models. OCT fundus images allow precise registration of OCT images and repeated measurements with respect to retinal fundus features. Three-dimensional OCT imaging enables visualization and quantification of retinal structure, which promises to allow repeated, noninvasive measurements to track disease progression, thereby reducing the need for killing the animal for histology. This capability can accelerate basic research studies in rats and mice and their translation into clinical patient care.

PURPOSE: Optic nerve head (ONH) structural imaging with state-of-the-art, high-speed, ultra-high-resolution optical coherence tomography (hsUHR-OCT). DESIGN: Observational cohort study. METHODS: ONH centered 3-dimensional (94,371,840 voxel measurements in a 6- x 6- x 1.4-mm tissue volume) hsUHR-OCT data were obtained in one eye from each of six males and nine females normal healthy volunteers (40 +/- 9 years of age). The presence of structures projecting anteriorly from the disk into the vitreous was noted. RESULTS: Structures were noted in 14 of 15 (93%) examined eyes, emanating from the rim of the ONH at the nasal inferior sector, presenting as thin tissue meandering into the vitreous. CONCLUSIONS: Previous technologies provided limited visualization of ONH structures. The ability to scan the entire disk using 3-dimensional OCT (3D-OCT) in a high-density raster pattern reveals a high frequency of persistence of Cloquet's canal in the normal healthy eye.

OBJECTIVE: To assess high-speed ultrahigh-resolution optical coherence tomography (OCT) image resolution, acquisition speed, image quality, and retinal coverage for the visualization of macular pathologies. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Five hundred eighty-eight eyes of 327 patients with various macular pathologies. METHODS: High-speed ultrahigh-resolution OCT images were obtained in 588 eyes of 327 patients with selected macular diseases. Ultrahigh-resolution OCT using Fourier/spectral domain detection achieves approximately 3-mum axial image resolutions, acquisition speeds of approximately 25 000 axial scans per second, and >3 times finer resolution and >50 times higher speed than standard OCT. Three scan protocols were investigated. The first acquires a small number of high-definition images through the fovea. The second acquires a raster series of high-transverse pixel density images. The third acquires 3-dimensional OCT data using a dense raster pattern. Three-dimensional OCT can generate OCT fundus images that enable precise registration of OCT images with the fundus. Using the OCT fundus images, OCT results were correlated with standard ophthalmoscopic examination techniques. MAIN OUTCOME MEASURES: High-definition macular pathologies. RESULTS: Macular holes, age-related macular degeneration, epiretinal membranes, diabetic retinopathy, retinal dystrophies, central serous chorioretinopathy, and other pathologies were imaged and correlated with ophthalmic examination, standard OCT, fundus photography, and fluorescein angiography, where applicable. High-speed ultrahigh-resolution OCT generates images of retinal pathologies with improved quality, more comprehensive retinal coverage, and more precise registration than standard OCT. The speed preserves retinal topography, thus enabling the visualization of subtle changes associated with disease. High-definition high-transverse pixel density OCT images improve visualization of photoreceptor and pigment epithelial morphology, as well as thin intraretinal and epiretinal structures. Three-dimensional OCT enables comprehensive retinal coverage, reduces sampling errors, and enables assessment of 3-dimensional pathology. CONCLUSIONS: High-definition 3-dimensional imaging using high-speed ultrahigh-resolution OCT improves image quality, retinal coverage, and registration. This new technology has the potential to become a useful tool for elucidating disease pathogenesis and improving disease diagnosis and management.

BACKGROUND: Limited data are available to guide optimal positioning of glaucoma drainage devices (GDD) in relation to the limbus and optic nerve. The authors aim to provide guidelines for appropriate and safe GDD implantation. METHOD: The optimal positioning of five different GDD were evaluated using necropsy eyes of varying axial lengths. The dependent variable that was measured was the maximum distance that a GDD could be placed posterior to the limbus while remaining 2 mm away from the optic nerve. RESULTS: The average maximum distance posterior to the limbus of the anterior plate edge ranged between 9.0-15.0 mm in the superotemporal quadrant for the GDD tested. The distances for superonasal, inferonasal, and inferotemporal quadrants ranged between 8.0-14.0 mm, 9.0-14.0 mm, and 11.0-17.0 mm, respectively. The Molteno device could be placed most posteriorly while remaining 2 mm away from the nerve. The Ahmed FP7 and S2 were the least amenable to posterior placement before encroaching on the 2 mm limit. CONCLUSION: The maximum distance that a GDD can be placed posterior to the limbus, before encroachment around the optic nerve, varies between different devices and quadrants of placement. Taking a measurement of the exact distance of the plate from the limbus during GDD surgery is recommended.

Overfiltering blebs can lead to postoperative problems including hypotony maculopathy, decreased vision, and increased ocular discomfort. Many methods have been used in the past with varying results. Various lasers have been used in an attempt to cause localized scarring and fibrosis. We report a treatment technique to noninvasively treat a patient with an overfiltering bleb using trypan blue and a frequency-doubled continuous-wave neodymium:YAG laser emitting green light.

OBJECTIVE: To compare the detection of clinically significant diabetic macular edema (DME) by an optical coherence tomography (OCT) grid scanning protocol and biomicroscopic examination. DESIGN: Retrospective case series. PARTICIPANTS: Outpatients at the Doheny Eye Institute. METHODS: The clinical and imaging records of a consecutive series of 71 eyes of 40 patients referred for DME who underwent OCT using the both the Macular Grid 5 (MG5) scanning protocol (to allow a more evenly distributed sampling of points in the macula) and the standard Fast Macular Thickness Map (FMTM) pattern were reviewed. An automated algorithm was developed to generate a retinal thickness map using the MG5 data, which was then compared with a normative database to identify presumed areas of retinal edema. Clinically significant macular edema (CSME) was also identified by clinical examination and stereoscopic fundus photographs for comparison with the results of the OCT protocols. MAIN OUTCOME MEASURES: Sensitivity and specificity of scanning protocols. RESULTS: Optical coherence tomograms were inspected visually, and automatically detected retinal boundaries were found to be correct in 69 of 71 MG5 scans and in 65 of 71 FMTM scans. Macular Grid 5 scanning was performed twice in each eye, and the repeatability (pooled standard deviation) of the total area of edema was 0.48 mm2 (coefficient of variation, 6.8%). Sensitivity and specificity of the MG5 for detection of CSME relative to the clinical examination were 89% and 86%, respectively, with kappa being 0.74. Macular Grid 5 and FMTM assessment of foveal CSME also showed good agreement, with kappa being 0.68. CONCLUSIONS: The analysis algorithm for the OCT MG5 grid scan seems to be accurate and repeatable. Automated detection of CSME by the MG5 analysis correlated well with the clinical grading and standard OCT analysis (FMTM). Macular Grid 5 provides more information regarding the perifoveal macula than FMTM and may be of value to clinicians in planning treatment and in future studies of macular edema.

OBJECTIVE: To demonstrate the ability to segment and analyze individual intraretinal layers, including the outer retinal complex (ORC; outer nuclear layer and inner and outer segments of the photoreceptor cells), in healthy eyes using images acquired from the latest commercially available optical coherence tomography (OCT) system (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA) and from the ultrahigh resolution OCT (UHR-OCT) prototype. METHODS: Thirty-seven eyes from 37 healthy subjects underwent complete ophthalmologic examination using StratusOCT and UHR-OCT. ORC was identified and measured using a segmentation algorithm. RESULTS: For StratusOCT, mean weighted ORC thickness +/- SD was 91.1 +/- 7.9 microm, and mean weighted total retinal thickness +/- SD was determined to be 258.9 +/- 10.1 microm. For UHR-OCT, mean weighted ORC thickness +/- SD was 96.4 +/- 6.3 microm, and mean weighted total retinal thickness +/- SD was determined to be 263.4 +/- 9.2 mum. There was a higher rate of algorithm failure with UHR-OCT images. CONCLUSIONS: Photoreceptor layer thickness can be calculated by measuring ORC on OCT images using a macular segmentation algorithm. ORC values may serve as a useful objective parameter in determining the efficacy of various therapeutic modalities that target the photoreceptor layer in various diseases.