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We developed an optical coherence photoacoustic microscopy (OC-PAM) system, which can accomplish optical coherence tomography (OCT) and photoacoustic microscopy (PAM) simultaneously by using a single pulsed broadband light source. With a center wavelength of 800 nm and a bandwidth of 30 nm, the system is suitable for imaging the retina. Generated from the same group of photons, the OCT and PAM images are intrinsically registered in the lateral directions. To test the capabilities of the system on multimodal ophthalmic imaging, we imaged the retina of pigmented rats. The OCT images showed the retinal structures with quality similar to conventional OCT, while the PAM images revealed the distribution of absorbers in the retina. Since the absorption of hemoglobin is relatively weak at around 800 nm, the NIR PAM signals are generated mainly from melanin in the posterior segment of the eye, thus providing melanin-specific imaging of the retina.

Photoacoustic ophthalmoscopy (PAOM) is a new retinal imaging technology that offers the unique capability to measure optical absorption in the retina. Because PAOM is compatible with optical coherence tomography, scanning laser ophthalmoscopy, and autofluorescence imaging, registered multimodal images can be acquired from a single device at comparable resolution for comprehensive anatomic and functional retinal characterizations. Therefore, PAOM is anticipated to have applications in both research and clinical diagnosis of many blinding diseases. The authors explain the basic principles of the photoacoustic effect and imaging. Then, different types of photoacoustic microscopy are introduced and compared. Finally, the current status of photoacoustic imaging in animal eyes is presented and the prospects of future development of PAOM are suggested., (Copyright 2011, SLACK Incorporated.)

Background and Objective: Diabetic macular edema has several patterns on optical coherence tomography. This retrospective study aimed to assess which retinal layers show thickness changes in type 1 diffuse diabetic macular edema with preserved vision., Patients and Methods: Eleven eyes with diffuse diabetic macular edema on optical coherence tomography and eight control eyes with 20/20 best-corrected visual acuity were enrolled. Optical coherence tomography images were segmented using an algorithm of the authors' design (OCTRIMA): regional thickness data in the central area, pericentral rings, and peripheral rings were obtained for the retinal cellular layers., Results: The retinal nerve fiber layer showed no changes, the ganglion cell and inner plexiform composite layer and the ganglion cell complex were thicker only in the pericentral regions, and all other layers were thicker in all regions in diffuse diabetic macular edema. Macular thickness was normal in the peripheral region., Conclusion: The results show that the outer retina in the foveal area is the most affected in diffuse diabetic macular edema., (Copyright 2010, SLACK Incorporated.)

Purpose: To reveal three-dimensional (3-D) information about the retinal structures of birds of prey in vivo., Methods: An ultra-high resolution spectral-domain optical coherence tomography (SD-OCT) system was built for in vivo imaging of retinas of birds of prey. The calibrated imaging depth and axial resolution of the system were 3.1 mm and 2.8 μm (in tissue), respectively. 3-D segmentation was performed for calculation of the retinal nerve fiber layer (RNFL) map., Results: High-resolution OCT images were obtained of the retinas of four species of birds of prey: two diurnal hawks (Buteo platypterus and Buteo brachyurus) and two nocturnal owls (Bubo virginianus and Strix varia). These images showed the detailed retinal anatomy, including the retinal layers and the structure of the deep and shallow foveae. The calculated thickness map showed the RNFL distribution. Traumatic injury to one bird's retina was also successfully imaged., Conclusions: Ultra-high resolution SD-OCT provides unprecedented high-quality 2-D and 3-D in vivo visualization of the retinal structures of birds of prey. SD-OCT is a powerful imaging tool for vision research in birds of prey.

We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 microm and 26.71 microm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 microm and 0.6 and 1.76 microm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R(2)>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.

We have developed a non-invasive photoacoustic ophthalmoscopy (PAOM) for in vivo retinal imaging. PAOM detects the photoacoustic signal induced by pulsed laser light shined onto the retina. By using a stationary ultrasonic transducer in contact with the eyelids and scanning only the laser light across the retina, PAOM provides volumetric imaging of the retinal micro-vasculature and retinal pigment epithelium at a high speed. For B-scan frames containing 256 A-lines, the current PAOM has a frame rate of 93 Hz, which is comparable with state-of-the-art commercial spectral-domain optical coherence tomography (SD-OCT). By integrating PAOM with SD-OCT, we further achieved OCT-guided PAOM, which can provide multi-modal retinal imaging simultaneously. The capabilities of this novel technology were demonstrated by imaging both the microanatomy and microvasculature of the rat retina in vivo.

We determine the reliability and reproducibility of retinal thickness measurements with a custom-built OCT retinal image analysis software (OCTRIMA). Ten eyes of five healthy subjects undergo repeated standard macular thickness map scan sessions by two experienced examiners using a Stratus OCT device. Automatic/semi automatic thickness quantification of the macula and intraretinal layers is performed using OCTRIMA software. Intraobserver, interobserver, and intervisit repeatability and reproducibility coefficients, and intraclass correlation coefficients (ICCs) per scan are calculated. Intraobserver, interobserver, and intervisit variability combined account for less than 5% of total variability for the total retinal thickness measurements and less than 7% for the intraretinal layers except the outer segment/ retinal pigment epithelium (RPE) junction. There is no significant difference between scans acquired by different observers or during different visits. The ICCs obtained for the intraobserver and intervisit variability tests are greater than 0.75 for the total retina and all intraretinal layers, except the inner nuclear layer intraobserver and interobserver test and the outer plexiform layer, intraobserver, interobserver, and intervisit test. Our results indicate that thickness measurements for the total retina and all intraretinal layers (except the outer segment/RPE junction) performed using OCTRIMA are highly repeatable and reproducible.

Purpose: To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography., Methods: Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-microm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients., Results: Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium-Bruch's membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47-1.68%; standard deviation, 0.55%)., Conclusion: The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

A prototype 6-microm axial resolution spectral domain optical coherence tomography (SD-OCT) device was used to image the retina of a patient with uncontrolled diabetes mellitus who had proliferative diabetic retinopathy with subhyaloid hemorrhage. A raster scan pattern with 128 B-scans covering a 6 X 6 X 2-mm volume of the retina was obtained. SD-OCT showed the presence of blood localized between the internal limiting membrane and the posterior hyaloid face and allowed visualization of the cross sectional retinal architecture and the vitreoretinal interface at different horizontal levels that could be registered with the color fundus photograph. SD-OCT provided useful information about the relationship of the hemorrhage to the posterior hyaloid and the retina.

Purpose: To study the inner surface of the retina in the presence of epiretinal membranes (ERMs) using a prototype spectral-domain optical coherence tomography (SD-OCT) device., Design: Small case series, performed in the Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, from August 2005 through December 2006., Method: An 8-microm axial-resolution SD-OCT instrument was used to scan the eyes of patients diagnosed with ERM. The ERM and the internal limiting membrane (ILM) were segmented separately to evaluate the traction caused by the ERM on the retina. It was then possible to reconstruct the ILM and ERM surfaces in 3-dimensional space and to obtain corresponding retinal thickness maps., Results: SD-OCT B scans showed the points of attachment of the ERM to the ILM. Segmented surface maps of the ERM produced very smooth sheets, whereas those of the ILM presented wrinkles under and around the ERM., Conclusions: SD-OCT revealed the geometry of retinal traction in eyes with ERM and may be useful in understanding further the pathologic features of these lesions.

The development of improved segmentation algorithms for more consistently accurate detection of retinal boundaries is a potentially useful solution to the limitations of existing optical coherence tomography (OCT) software. We modeled artifacts related to operator errors that may normally occur during OCT imaging and evaluated their influence on segmentation results using a novel segmentation algorithm. These artifacts included: defocusing, depolarization, decentration, and a combination of defocusing and depolarization. Mean relative reflectance and average thickness of the automatically extracted intraretinal layers was then measured. Our results show that defocusing and depolarization errors together have the greatest altering effect on all measurements and on segmentation accuracy. A marked decrease in mean relative reflectance and average thickness was observed due to depolarization artifact in all intraretinal layers, while defocus resulted in a less-marked decrease. Decentration resulted in a marked but not significant change in average thickness. Our study demonstrates that care must be taken for good-quality imaging when measurements of intraretinal layers using the novel algorithm are planned in future studies. An awareness of these pitfalls and their possible solutions is crucial for obtaining a better quantitative analysis of clinically relevant features of retinal pathology.

To determine whether bevacizumab could improve visual acuity and optical coherence tomography outcomes in a patient with macular edema from central retinal vein occlusion, an intravitreal injection of bevacizumab (1.0 mg) was given. Prior intravitreal injections of triamcinolone acetonide resulted in vision improvement but worsening cataract and borderline glaucoma. Within 1 week of the bevacizumab injection, visual acuity improved from 20/200 to 20/50 and optical coherence tomography revealed resolution of the cystic maculopathy. The improvements were maintained for at least 4 weeks. Intravitreal injections of bevacizumab may provide another treatment option for patients with macular edema from vein occlusions.

Purpose: To quantitatively evaluate the retinal microvasculature in human subjects with retinal venous occlusions (RVO) using optical coherence tomography angiography (OCTA). Design: Retrospective, cross-sectional, observational case series. Participants: Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO, 24 unaffected fellow eyes, and 26 controls). Methods: OCTA was performed on a prototype, spectral domain-OCTA system in the 3x3mm central macular region. Custom software was used to quantify morphology and density of retinal capillaries using four quantitative parameters. The vasculature of the segmented retinal layers and nonsegmented whole retina were analyzed. Main outcome measures: Fractal dimension (FD), vessel density (VD), skeletal density (SD), and vessel diameter index (VDI) within the segmented retinal layers and nonsegmented whole retina vasculature. Results: Nonsegmented analysis of RVO eyes demonstrated significantly lower FD (1.64±0.01 vs 1.715±0.002; p<0.001), VD (0.32±0.01 vs 0.432±0.002; p<0.001), and SD (0.073±0.004 vs 0.099±0.001; p<0.001) compared to controls. Compared to the fellow eye, FD, VD and SD were lower (p<0.001), and VDI was higher (p<0.001). FD, VD, and SD progressively decreased as the extent (or type) of RVO increased (control vs BRVO vs CRVO; p<0.001). In the unaffected fellow eye FD, VD and SD showed significant differences when compared to control eyes or affected RVO eyes (p<0.001). Conclusions: Quantitative OCTA of the central 3x3mm macular region demonstrates significant differences in capillary density and morphology among subjects with BRVO and CRVO compared to controls or unaffected fellow eyes in all vascular layers. The unaffected fellow eyes also demonstrate significant differences when compared to controls. OCTA allows for noninvasive, layer-specific, quantitative evaluation of RVO-associated microvascular changes. [ABSTRACT FROM AUTHOR]

Purpose: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD).Design: Retrospective interventional case series.Methods: Ninety eyes (88 patients) with AMD and predominantly classic subfoveal CNV treated with PDT using verteporfin were identified by a laser log and retrospectively reviewed. Optical coherence tomography and fluorescein angiography (FA) were performed before treatment and at subsequent follow-up examinations in all eyes. Optical coherence tomography findings were evaluated and compared with corresponding FA.Results: A five-stage OCT classification of eyes treated with PDT was created from the evaluation of 79 total eyes (77 patients). Stage I (two eyes) is recognized within the first week of treatment and demonstrates an acute inflammatory response with increased subretinal fluid. Stage II (28 eyes) represents the restoration of a near-normal fovea contour with diminished subretinal fluid occurring 1 to 4 weeks after treatment. Stage III (79 eyes) occurs between 4 to 12 weeks following treatment and is subdivided into two categories based on the amount of subretinal fibrosis and fluid present. Stage IIIa (15 eyes) contains a greater subretinal fluid to fibrosis ratio indicating an active CNV process. Lesions in stage IIIb (64 eyes) less actively leak and have more prominent fibrosis with minimal intraretinal fluid. Cystoid macular edema defines a stage IV lesion (11 eyes). In stage V lesions (19 eyes) the subretinal fluid resolves with thinning of the retina as well as fibrosis merging with the retinal pigment epithelial layer (RPE).Conclusion: Optical coherence tomography appears to be useful in monitoring the retinal changes that occur following PDT of CNV and may assist in understanding the changes observed on angiography. [ABSTRACT FROM AUTHOR]