Faculty Bibliography

OBJECTIVE: To evaluate intraretinal anatomy in patients with exudative age-related macular degeneration (AMD) using high-speed ultrahigh resolution optical coherence tomography (hsUHR-OCT) before and 1 month after intravitreal injection of ranibizumab. DESIGN: Retrospective case series. PARTICIPANTS: Twelve eyes of 12 patients. METHODS: A broad bandwidth superluminescent diode laser light source and spectral/Fourier domain signal detection were used to create a prototype hsUHR-OCT instrument with 3.5 mum axial image resolution and approximately 25,000 lines/second acquisition speed. Twelve eyes of 12 patients with exudative AMD were imaged with hsUHR-OCT before and 1 month after intravitreal ranibizumab injection. High pixel density and raster-scanned 3-dimensional (3D) OCT data sets were generated. Three-dimensional imaging software was used to calculate subretinal/retinal pigment epithelium fluid volume and volume of the fibrovascular lesion. MAIN OUTCOME MEASURES: Qualitative and quantitative analysis of hsUHR-OCT images and 3D data sets. RESULTS: All eyes had some degree of normalization of macular contour after intravitreal ranibizumab. The inner/outer photoreceptor segment junction visualized on hsUHR-OCT was discontinuous, overlying the fibrovascular lesion in all 12 of 12 eyes both before and after treatment; 9 of 12 eyes had focal areas of thinning of the outer nuclear layer, which remained after treatment. Volumetric measurements were possible in 8 of 12 eyes with 3D-rendering software. Fibrovascular lesion volume did not change significantly after treatment. CONCLUSIONS: hsUHR-OCT is capable of unprecedented imaging speed and resolution, making it a valuable instrument in measuring in vivo intraretinal pathology. All 12 eyes had some normalization of macular contour. Fibrovascular lesion volume did not change significantly 1 month after treatment, suggesting that ranibizumab does not cause much initial regression of preexisting neovascular tissue. Photoreceptor abnormalities remained in all patients after treatment of wet AMD, suggesting that although ranibizumab improves overall retinal architecture, some photoreceptor damage may be irreversible. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

AIMS: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). METHODS: A high-speed, 3.5 mum resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. RESULTS: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. CONCLUSIONS: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

Optical coherence tomography has allowed unprecedented visualization of ocular structures, but the identity of some visible objects within slices remains unknown. This study reconstructs a number of those objects in 3D space, allowing their identification by observation of their 3D morphology. In the case mottling deep within image slices through the optic disc, C-mode imaging provided visualization of the appearance and distribution of laminar pores. In the case of white spots and streaks sometimes observed in image slices through the cornea, C-mode imaging contoured to the path of those white spots allowed their visual identification as nerves extending radially into the cornea from the limbus. White spots observed in ultra-high resolution retinal image slices were identified as blood within retinal capillaries. C-mode contour-corrected imaging of three dimensional structures provided the identification of previously unidentified structures visible in cross-sectional image slices.

The Optical Society (OSA) is pleased to present this special issue of Optics Express on "Optical Coherence Tomography (OCT) in Ophthalmology" as part of the new Interactive Science Publishing (ISP) project. The project is being performed in collaboration with the National Library of Medicine and represents a new paradigm for the publication of digital image and large dataset information.

Ultrahigh resolution optical coherence tomography (OCT) enhances the ability to visualize different intra retinal layers. In age-related macular degeneration (AMD), pathological changes in individual retinal layers, including photoreceptor inner and outer segments and retinal pigment epithelium, can be detected. OCT using spectral / Fourier domain detection enables high speed, volumetric imaging of the macula, which provides comprehensive three-dimensional tomographic and morphologic information. We present a case series of AMD patients, from mild drusen to more advanced geographic atrophy and exudative AMD. Patients were imaged with a research prototype, ultrahigh resolution spectral / Fourier domain OCT instrument with 3.5 microm axial image resolution operating at 25,000 axial scans per second. These cases provide representative volumetric datasets of well-documented AMD pathologies which could be used for the development of visualization and imaging processing methods and algorithms.

PURPOSE: To develop a semiautomated method to visualize structures of interest (SoIs) along their contour within three-dimensional, spectral domain optical coherence tomography (3D SD-OCT) data, without the need for segmentation. METHODS: With the use of two SD-OCT devices, the authors obtained 3D SD-OCT data within 6 x 6 x 1.4-mm and 6 x 6 x 2-mm volumes, respectively, centered on the fovea in healthy eyes and in eyes with retinal pathology. C-mode images were generated by sampling a variable thickness plane semiautomatically modeled to fit the contour of the SoI. Unlike published and commercialized methods, this method did not require retinal layer segmentation, which is known to fail frequently in the presence of retinal pathology. Four SoIs were visualized for healthy eyes: striation of retinal nerve fiber (RNF), retinal capillary network (RCN), choroidal capillary network (CCN), and major choroidal vasculature (CV). Various SoIs were visualized for eyes with retinal pathology. RESULTS: Seven healthy eyes and seven eyes with retinal pathology (cystoid macular edema, central serous retinopathy, vitreoretinal traction, and age-related macular degeneration) were imaged. CCN and CV were successfully visualized in all eyes, whereas RNF and RCN were visualized in all healthy eyes and in 42.8% of eyes with pathologies. Various SoIs were successfully visualized in all eyes with retinal pathology. CONCLUSIONS: The proposed C-mode contour modeling may provide clinically useful images of SoIs even in eyes with severe pathologic changes in which segmentation algorithms fail.

BACKGROUND AND OBJECTIVE: A retrospective cross-sectional study was conducted to demonstrate an analysis of an outer retinal layer reconstructed by the three-dimensional and high-speed spectral domain optical coherence tomography (SD-OCT) instrument. PATIENTS AND METHODS: New measurement protocols for SD-OCT and methods of analysis and visualization of the individual segmented retinal layer reconstructed by SD-OCT were proposed. Three contour maps representing mutual distances between the basal part of the retinal pigment epithelium, the junction between the inner and outer segments of photoreceptors, and a reference contour representing the shape of a healthy retina were introduced. RESULTS: The analysis of the outer retina was performed on pathological eyes. Three cases of central serous chorioretinopathy, age-related macular degeneration, and acute zonal occult outer retinopathy are demonstrated. CONCLUSION: Three contour maps reconstructed for clinical cases demonstrate high variability of observed patterns depending on analyzed pathology. The authors believe this can help to present OCT data simultaneously in a more comprehensive and convenient way to assist in everyday clinical diagnosis.

PURPOSE: To validate velocity measurements produced by spectral domain optical coherence tomography (SD-OCT) in an in vitro laminar flow model. METHODS: A 30-mL syringe filled with skim milk was inserted into a syringe pump. Intravenous (i.v.) tubing connected the syringe within the pump to a glass capillary tube (internal diameter, 0.579 mm) shallowly embedded in agarose gel, then to a collection reservoir. SD-OCT imaging was performed with an anterior segment eye scanner and optics engine coupled with a 100-nm bandwidth broadband superluminescent diode. Scan density of 128 x 128 A-scans was spread over a 4 x 4 mm area, and each A-scan was 2 mm in length. Fifteen sequential stationary A-scans were obtained at each 128 x 128 position, and Doppler shifts were calculated from temporal changes in phase. The beam-to-flow vector Doppler angle was determined from three-dimensional scans. RESULTS: In all reflectance and Doppler images, a clear laminar flow pattern was observed, with v(max) appearing in the center of the flow column. Phase wrapping was observed at all measured flow velocities, and fringe washout progressively shattered reflectance and phase signals beyond the Nyquist limit. The observed percentages of the velocity profile at or below Nyquist frequency was highly correlated with the predicted percentages (R(2)=0.934; P=0.007). CONCLUSIONS: SD-OCT provides objective Doppler measurements of laminar fluid flow in an in vitro flow system in a range up to the Nyquist limit.

BACKGROUND: Glaucoma is a group of diseases characterised by retinal ganglion cell dysfunction and death. Detection of glaucoma and its progression are based on identification of abnormalities or changes in the optic nerve head (ONH) or the retinal nerve fibre layer (RNFL), either functional or structural. This review will focus on the identification of structural abnormalities in the RNFL associated with glaucoma. DISCUSSION: A variety of new techniques have been created and developed to move beyond photography, which generally requires subjective interpretation, to quantitative retinal imaging to measure RNFL loss. Scanning laser polarimetry uses polarised light to measure the RNFL birefringence to estimate tissue thickness. Optical coherence tomography (OCT) uses low-coherence light to create high-resolution tomographic images of the retina from backscattered light in order to measure the tissue thickness of the retinal layers and intraretinal structures. Segmentation algorithms are used to measure the thickness of the retinal nerve fibre layer directly from the OCT images. In addition to these clinically available technologies, new techniques are in the research stages. Polarisation-sensitive OCT has been developed that combines the strengths of scanning laser polarimetry with those of OCT. Ultra-fast techniques for OCT have been created for research devices. The continued utilisation of imaging devices into the clinic is refining glaucoma assessment. In the past 20 years glaucoma has gone from a disease diagnosed and followed using highly subjective techniques to one measured quantitatively and increasingly objectively.

Spectral domain optical coherence tomography (SD-OCT) is an important tool for the diagnosis of various retinal diseases. The measurements available from SD-OCT volumes can be used to detect structural changes in glaucoma patients before the resulting vision loss becomes noticeable. Eye movement during the imaging process corrupts the data, making measurements unreliable. We propose a method to correct for transverse motion artifacts in SD-OCT volumes after scan acquisition by registering the volume to an instantaneous, and therefore artifact-free, reference image. Our procedure corrects for smooth deformations resulting from ocular tremor and drift as well as the abrupt discontinuities in vessels resulting from microsaccades. We test our performance on 48 scans of healthy eyes and 116 scans of glaucomatous eyes, improving scan quality in 96% of healthy and 73% of glaucomatous eyes.