Correlation between optic disc perfusion and glaucomatous severity in patients with open-angle glaucoma: an optical coherence tomography angiography study.

PURPOSE: To explore how optic disc perfusion varies in patients with open-angle glaucoma (OAG) and how this correlates with glaucoma severity. METHODS: We performed a prospective and cross-sectional observational study that included 62 eyes from 62 patients with OAG, divided into three groups according to their visual field (VF) results, and 20 eyes from 20 normal control subjects. Optic disc perfusion was studied using optical coherence tomography angiography (angio-OCT), and flow index and vessel density were determined. The VF, mean deviation (MD), pattern standard deviation (PSD), retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness were also recorded. The potential associations between disc perfusion and VF defects or structural loss were analyzed. RESULTS: In OAG patients, the disc flow index and vessel density were significantly lower than in normal controls (all p<0.001) and were correlated with the severity of glaucoma. In OAG eyes, the flow index and vessel density were significantly correlated with MD, RNFL, and GCC thickness (all p<0.01), but were not in the normal controls. The receiver operating characteristic (ROC) curve analysis also revealed that disc flow index and vessel density had the power to differentiate normal eyes from eyes with OAG (under the ROC curves: 0.82 and 0.80, respectively). CONCLUSIONS: Angiograms demonstrated a reduced disc flow index and vessel density in glaucoma, and this reduction was closely related to GCC thickness. This indicated that measurement of disc perfusion by angio-OCT might be important for the monitoring of glaucoma.

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.

An Analysis of the Effect of ABCA4 p.Asn1868Ile Genotypes on Retinal Structure in 26,558 Participants in the UK Biobank.

Purpose: To determine whether the ABCA4 retinopathy-associated variant p.Asn1868Ile (c.5603A>T) is associated with retinal structure or subclinical disease among the general population. Methods: UK Biobank participants of European ancestry with available spectral-domain optical coherence tomography (OCT) passing quality control metrics and exome sequencing data were included. Regression analyses using both linear and recessive models tested for the association between the p.Asn1868Ile variant and total retinal thickness, clinically relevant segmented layer thicknesses, and visual acuity. Further regression analyses were performed with automated quality control metrics to determine if the p.Asn1868Ile variant is associated with poor quality or abnormal scans. Results: Retinal layer segmentation and sequencing data for the p.Asn1868Ile variant were available for 26,558 participants, following exclusions. We identified no significant association between the p.Asn1868Ile variant and retinal thickness, any of the segmented layers, or visual acuity. There was also no significant difference for homozygous p.Asn1868Ile when tested under the assumption of a recessive model. No association was identified for any of the quality control metrics, and a χ2 test showed that participants with the p.Asn1868Ile variant were not more likely to be excluded during quality control due to poor quality scans (P = 0.56). Conclusions: The p.Asn1868Ile variant does not appear to affect the retinal structure or have pathogenic or subclinical effects on its own within the general population. The variant is likely to require other specific cis- or trans-acting modifying factors to cause ABCA4 retinopathy.

Associations Between HbA1c Across the Normal Range, Diagnosed, and Undiagnosed Diabetes and Retinal Layer Thickness in UK Biobank Cohort.

Purpose: The purpose of this study was to investigate the association between glycated hemoglobin (HbA1c) levels and retinal sub-layer thicknesses in people with and without diabetes. Methods: We included 41,453 UK Biobank participants aged 40 to 69 years old. Diabetes status was defined by self-report of diagnosis or use of insulin. Participants were categorized into groups: (1) those with HbA1c <48 mmol/mol were subdivided into quintiles according to normal range of HbA1c; (2) those previously diagnosed with diabetes with no evidence of diabetic retinopathy; and (3) undiagnosed diabetes: >48 mmol/mol. Total macular and retinal sub-layer thicknesses were derived from spectral-domain optical coherence tomography (SD-OCT) images. Multivariable linear regression was used to evaluate the associations between diabetes status and retinal layer thickness. Results: Compared with participants in the second quintile of the normal HbA1c range, those in the fifth quintile had a thinner photoreceptor layer thickness (-0.33 µm, P = 0.006). Participants with diagnosed diabetes had a thinner macular retinal nerve fiber layer (mRNFL; -0.58 µm, P < 0.001), photoreceptor layer thickness (-0.94 µm, P < 0.001), and total macular thickness (-1.61 µm, P < 0.001), whereas undiagnosed diabetes participants had a reduced photoreceptor layer thickness (-1.22 µm, P = 0.009) and total macular thickness (-2.26 µm, P = 0.005). Compared to participants without diabetes, those with diabetes had a thinner mRNFL (-0.50 µm, P < 0.001), photoreceptor layer thickness (-0.77 µm, P < 0.001), and total macular thickness (-1.36 µm, P < 0.001). Conclusions: Participants with higher HbA1c in the normal range had marginally thinner photoreceptor thickness, whereas those with diabetes (including undiagnosed diabetes) had meaningfully thinner retinal sublayer and total macular thickness. Translational Relevance: We showed that early retinal neurodegeneration occurs in people whose HbA1c levels are below the current diabetes diagnostic threshold; this might impact the management of pre-diabetes individuals.

High-speed, miniaturized fluorescence microscopy in freely moving mice.

A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca(2+) dynamics.

Noninvasive volumetric imaging and morphometry of the rodent retina with high-speed, ultrahigh-resolution optical coherence tomography.

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.

Ultrahigh-resolution optical coherence tomography in patients with decreased visual acuity after retinal detachment repair.

OBJECTIVE: To assess microstructural changes in the retina that may explain incomplete visual recovery after anatomically successful repair of rhegmatogenous retinal detachments (RD) using ultrahigh-resolution optical coherence tomography (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Seventeen patients with decreased visual acuity after RD repair. Twelve patients had macula-involving and 5 had macula-sparing RDs. METHODS: The UHR OCT prototype capable of approximately 3 mum axial resolution was developed for clinical use. The UHR OCT images through the center of the fovea in 17 patients with visual complaints after RD surgery were obtained. Patients were either postoperative patients from the New England Eye Center or tertiary referrals. Baseline visual acuity, preoperative lens status, location of retinal detachment, macular involvement, and postoperative visual acuity were recorded. MAIN OUTCOME MEASURES: The UHR OCT images after RD repair. RESULTS: The UHR OCT images were obtained 1 to 84 months (median, 5 months) postoperatively. The mean preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.37 (Snellen equivalent, 20/390). The mean postoperative logMAR visual acuity was 0.48 (Snellen equivalent, 20/60). Anatomical abnormalities that were detected included distortion of the photoreceptor inner/outer segments (IS/OS) junction in 14 of 17 patients (82%), epiretinal membranes in 10 of 17 patients (59%), residual subretinal fluid in 3 of 17 patients (18%), and cystoid macular edema in 2 of 17 patients (12%). Of the 5 patients with preoperative macula-on detachments, 4 had distortion of the outer retina after RD repair. CONCLUSIONS: The higher resolution of UHR OCT facilitates imaging of the IS/OS junction. Therefore, UHR OCT is able to confirm prior histopathologic findings that damage to photoreceptor outer segments may occur as a consequence of retinal detachment. This may explain poor postoperative visual acuity in eyes with anatomically successful repair.

Redefining lamellar holes and the vitreomacular interface: an ultrahigh-resolution optical coherence tomography study.

OBJECTIVES: To define optical coherence tomographic (OCT) criteria for the diagnosis of a lamellar macular hole, and to increase understanding of lamellar hole pathogenesis by examining fine anatomic features using ultrahigh-resolution optical coherence tomography (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Nineteen eyes of 18 patients with lamellar holes were imaged with UHR OCT between 2002 and 2004. METHODS: A UHR OCT system was developed for use in the ophthalmology clinic. All 6 UHR OCT images for each eye imaged were examined. Lamellar holes were diagnosed based on a characteristic OCT appearance. Criteria for the OCT diagnosis of a lamellar hole were as follows: (1) irregular foveal contour; (2) break in the inner fovea; (3) intraretinal split; and (4) intact foveal photoreceptors. From 1205 eyes of 664 patients imaged with UHR OCT, and retrospectively reviewed, 19 eyes of 18 patients were diagnosed with a lamellar hole based on these criteria. All 19 eyes were also imaged with standard resolution OCT. Their charts were retrospectively reviewed. MAIN OUTCOME MEASURES: Standard and ultrahigh-resolution OCT images. RESULTS: On chart review, clinical diagnosis of a lamellar hole was made in only 7 of 19 eyes (37%). Twelve of 19 eyes (63%) had an epiretinal membrane (ERM) on clinical examination. Ten of 19 eyes (53%) had a posterior vitreous detachment. On UHR OCT, 17 of 19 eyes (89%) had ERMs. Eleven ERMs had an unusual thick appearance on UHR OCT. Due to poor visual acuity, 4 eyes underwent vitrectomy. Only 1 of 4 surgeries (25%) was visually and anatomically successful. Another eye improved visually, but a lamellar hole persisted. One eye progressed to a full-thickness macular hole preoperatively, which reopened after surgery. One eye developed a full-thickness hole postoperatively. CONCLUSIONS: The diagnosis of a lamellar hole can be made based on OCT criteria, which could be applied to both standard and ultrahigh-resolution OCT. The increased resolution of UHR OCT sheds light on the pathogenesis of the lamellar hole. Epiretinal membranes were visualized on UHR OCT in the majority of eyes. Many ERMs had an unusual thick appearance on UHR OCT, which may represent either trapped vitreous or posterior hyaloid, and may help stabilize retinal anatomy. Conversely, ERM contraction may play a role in lamellar hole formation. Vitrectomy surgery was anatomically and visually successful in only 1 of 4 patients, suggesting caution when performing vitrectomy on lamellar holes.

Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography.

OBJECTIVE: To investigate the capabilities of ultrahigh-resolution optical coherence tomography (UHR OCT); to compare with the commercially available OCT standard-resolution system, StratusOCT, for imaging of idiopathic juxtafoveal retinal telangiectasis (IJT); and to demonstrate that UHR OCT provides additional information on disease morphology, pathogenesis, and management. DESIGN: Retrospective, observational, interventional case series. PARTICIPANTS: Nineteen eyes of 10 patients diagnosed with IJT in at least one eye. METHOD: All patients were imaged with UHR OCT and StratusOCT at the same visit. A subset of patients was also imaged before and after treatment of IJT. MAIN OUTCOME MEASURES: Ultrahigh- and standard-resolution cross-sectional tomograms of IJT pathology. RESULTS: Using both standard- and ultrahigh-resolution OCT, we identified the following features of IJT: (1) a lack of correlation between retinal thickening on OCT and leakage on fluorescein angiography, (2) loss and disruption of the photoreceptor layer, (3) cystlike structures in the foveola and within internal retinal layers such as the inner nuclear or ganglion cell layers, (4) a unique internal limiting membrane draping across the foveola related to an underlying loss of tissue, (5) intraretinal neovascularization near the fovea, and (6) central intraretinal deposits and plaques. In 63% of cases, the presence of abnormal vessels and a discontinuity of the photoreceptor layer correlated with visual acuity. CONCLUSIONS: Ultrahigh-resolution OCT improves visualization of the retinal pathology associated with IJT and allows identification of new features associated with it. Some of these features, such as discontinuity of the photoreceptor layer, are revealed only by UHR OCT.

High-definition and 3-dimensional imaging of macular pathologies with high-speed ultrahigh-resolution optical coherence tomography.

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.

Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography.

OBJECTIVE: To report normal macular thickness measurements in healthy eyes using the latest commercially available optical coherence tomography (OCT) mapping software, version 3.0, from the Stratus OCT (OCT3). METHODS: Thirty-seven eyes from 37 healthy subjects underwent a complete ophthalmologic examination, including OCT. Six radial scans, 6 mm in length and centered on the fovea, were obtained using the OCT3. Retinal thickness was automatically calculated by OCT mapping software. Measurements were displayed as the mean and standard deviation for each of the 9 regions defined in the Early Treatment Diabetic Retinopathy Study. RESULTS: Foveal thickness (mean thickness in the central 1000-microm diameter area) and central foveal thickness (mean thickness at the point of intersection of 6 radial scans) on the OCT3 were 212 +/- 20 and 182 +/- 23 microm, respectively. Macular thickness measurements were thinnest at the center of the fovea, thickest within 3-mm diameter of the center, and diminished toward the periphery of the macula. The temporal quadrant was thinner than the nasal quadrant. Central foveal thickness was also manually determined as 170 +/- 18 microm, approximately 12 microm less than the value automatically obtained from the OCT3 software. There was no correlation between age and foveal thickness (P = .80). CONCLUSIONS: Mean foveal thickness measurements were 38 to 62 microm thicker than previously reported values, while mean central foveal thickness measurements were 20 to 49 microm thicker than previously published values. This discrepancy should be considered when interpreting OCT scans.

Ultrahigh-resolution optical coherence tomography of surgically closed macular holes.

OBJECTIVE: To evaluate retinal anatomy using ultrahigh-resolution optical coherence tomography (OCT) in eyes after successful surgical repair of full-thickness macular hole. METHODS: Twenty-two eyes of 22 patients were diagnosed as having macular hole, underwent pars plana vitrectomy, and had flat/closed macular anatomy after surgery, as confirmed with biomicroscopic and OCT examination findings. An ultrahigh-resolution-OCT system developed for retinal imaging, with the capability to achieve approximately 3-microm axial resolution, was used to evaluate retinal anatomy after hole repair. RESULTS: Despite successful closure of the macular hole, all 22 eyes had macular abnormalities on ultrahigh-resolution-OCT images after surgery. These abnormalities were separated into the following 5 categories: (1) outer foveal defects in 14 eyes (64%), (2) persistent foveal detachment in 4 (18%), (3) moderately reflective foveal lesions in 12 (55%), (4) epiretinal membranes in 14 (64%), and (5) nerve fiber layer defects in 3 (14%). CONCLUSIONS: With improved visualization of fine retinal architectural features, ultrahigh-resolution OCT can visualize persistent retinal abnormalities despite anatomically successful macular hole surgery. Outer foveal hyporeflective disruptions of the junction between the inner and outer segments of the photoreceptors likely represent areas of foveal photoreceptor degeneration. Moderately reflective lesions likely represent glial cell proliferation at the site of hole reapproximation. Thin epiretinal membranes do not seem to decrease visual acuity and may play a role in reestablishing foveal anatomy after surgery.

Ultra-high resolution optical coherence tomography assessment of photoreceptors in retinitis pigmentosa and related diseases.

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.

Ultrahigh-resolution optical coherence tomography of canthaxanthine retinal crystals.

A case of crystalline retinopathy caused by prolonged ingestion of an oral tanning agent containing canthaxanthine is described. Color fundus photography and ultrahigh-resolution optical coherence tomography were performed.

Assessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography.

PURPOSE: To assess photoreceptor morphology in patients with Stargardt's disease and fundus flavimaculatus using ultrahigh-resolution optical coherence tomography (UHR-OCT) and correlate it with visual acuity (VA). METHODS: This was a prospective observational case series. Fourteen patients with Stargardt's disease (nine women, five men; average age, 39 years; range, 27-53) were examined. A clinically viable UHR-OCT system employing a new, compact titanium sapphire laser was used, enabling a 3-microm axial resolution in the retina. All patients received a full ophthalmic examination, including fluorescein angiography. Outcome was judged by central transverse photoreceptor loss, central foveal thickness, VA, central atrophy according to fluorescein angiography, and fundus autofluorescence. RESULTS: UHR-OCT was capable of visualizing and quantifying regions of central transverse photoreceptor (PR) loss. All Stargardt patients with central atrophy had a complete loss of the central photoreceptor layer in the foveal region (mean transverse photoreceptor loss, 4390 +/- 2270 microm; range, 530-9240 microm). Patients without clinically evident central atrophy had an intact photoreceptor layer centrally, but had small, focal parafoveal defects. A correlation was detected between VA and transverse PR loss (Spearman rho=-0.60, P=0.03), which was confirmed on logistic regression analysis (R2=0.49, P=0.0001). Central foveal thickness was reduced in patients with Stargardt's disease (85 +/- 40 microm; range, 58-280 microm). The correlation was statistically significant with VA (Spearman rho=0.43, P=0.04), but not with transverse PR loss (Spearman rho=-0.23, P >>0.05). Linear regression analysis showed a statistically significant association of central foveal thickness with VA (R2=0.51, P=0.0001), but not with transverse PR loss (P >>0.05). The extent of atrophy seen in fluorescein angiography correlated with VA and transverse PR loss (Spearman rho=-0.51, P=0.007; Spearman rho=0.77, P=0.0001). Similar correlations were found with the maximum transverse diameter of fundus autofluorescence (Spearman rho=-0.72, P=0.008; Spearman rho=0.77, P=0.003). CONCLUSIONS: Ultrahigh-resolution OCT demonstrates excellent visualization of intraretinal morphology and enables quantification of the photoreceptor layer. Thus, for the first time, an in vivo visualization and quantification of transverse, central photoreceptor loss and correlation with visual function is possible. Lower VA corresponds to a greater transverse photoreceptor loss, which also correlates with the extent of changes seen in fluorescein angiography and in fundus autofluorescence. Furthermore, reduced retinal thickness (i.e., atrophy of retinal layers) does not correlate with the transverse extent of PR loss. Thus, it seems that although there may be progressive atrophy of intraretinal layers, an intact photoreceptor layer leads to better VA. UHR-OCT may present a viable alternative to the assessment of central visual function, due to the easy, objective, and noninvasive data acquisition. Therefore, UHR-OCT could be of future use in judging patients' prognoses in Stargardt's disease.

Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography.

PURPOSE: To demonstrate high-speed, ultrahigh-resolution, 3-dimensional optical coherence tomography (3D OCT) and new protocols for retinal imaging. METHODS: Ultrahigh-resolution OCT using broadband light sources achieves axial image resolutions of approximately 2 microm compared with standard 10-microm-resolution OCT current commercial instruments. High-speed OCT using spectral/Fourier domain detection enables dramatic increases in imaging speeds. Three-dimensional OCT retinal imaging is performed in normal human subjects using high-speed ultrahigh-resolution OCT. Three-dimensional OCT data of the macula and optic disc are acquired using a dense raster scan pattern. New processing and display methods for generating virtual OCT fundus images; cross-sectional OCT images with arbitrary orientations; quantitative maps of retinal, nerve fiber layer, and other intraretinal layer thicknesses; and optic nerve head topographic parameters are demonstrated. RESULTS: Three-dimensional OCT imaging enables new imaging protocols that improve visualization and mapping of retinal microstructure. An OCT fundus image can be generated directly from the 3D OCT data, which enables precise and repeatable registration of cross-sectional OCT images and thickness maps with fundus features. Optical coherence tomography images with arbitrary orientations, such as circumpapillary scans, can be generated from 3D OCT data. Mapping of total retinal thickness and thicknesses of the nerve fiber layer, photoreceptor layer, and other intraretinal layers is demonstrated. Measurement of optic nerve head topography and disc parameters is also possible. Three-dimensional OCT enables measurements that are similar to those of standard instruments, including the StratusOCT, GDx, HRT, and RTA. CONCLUSION: Three-dimensional OCT imaging can be performed using high-speed ultrahigh-resolution OCT. Three-dimensional OCT provides comprehensive visualization and mapping of retinal microstructures. The high data acquisition speeds enable high-density data sets with large numbers of transverse positions on the retina, which reduces the possibility of missing focal pathologies. In addition to providing image information such as OCT cross-sectional images, OCT fundus images, and 3D rendering, quantitative measurement and mapping of intraretinal layer thickness and topographic features of the optic disc are possible. We hope that 3D OCT imaging may help to elucidate the structural changes associated with retinal disease as well as improve early diagnosis and monitoring of disease progression and response to treatment.

Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular pathology.

OBJECTIVE: To compare ultrahigh-resolution optical coherence tomography (UHR OCT) with standard-resolution OCT for imaging macular diseases, develop baselines for interpreting OCT images, and identify situations where UHR OCT can provide additional information on disease morphology. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two eyes of 555 patients with different macular diseases including macular hole, macular edema, central serous chorioretinopathy, age-related macular degeneration (AMD), choroidal neovascularization, epiretinal membrane, retinal pigment epithelium (RPE) detachment, and retinitis pigmentosa. METHODS: A UHR ophthalmic OCT system that achieves 3-microm axial image resolution was developed for imaging in the ophthalmology clinic. Comparative studies were performed with both UHR OCT and standard 10-microm-resolution OCT. Standard scanning protocols of 6 radial 6-mm scans through the fovea were obtained with both systems. Ultrahigh-resolution OCT and standard-resolution OCT images were correlated with standard ophthalmic examination techniques (dilated ophthalmoscopy, fluorescein angiography, indocyanine green angiograms) to assess morphological information contained in the images. MAIN OUTCOME MEASURES: Ultrahigh-resolution and standard-resolution OCT images of macular pathologies. RESULTS: Correlations of UHR OCT images, standard-resolution images, fundus examination, and/or fluorescein angiography were demonstrated in full-thickness macular hole, central serous chorioretinopathy, macular edema, AMD, RPE detachment, epiretinal membrane, vitreal macular traction, and retinitis pigmentosa. Ultrahigh-resolution OCT and standard-resolution OCT exhibited comparable performance in differentiating thicker retinal layers, such as the retinal nerve fiber, inner and outer plexiform, and inner and outer nuclear. Ultrahigh-resolution OCT had improved performance differentiating finer structures or structures with lower contrast, such as the ganglion cell layer and external limiting membrane. Ultrahigh-resolution OCT confirmed the interpretation of features, such as the boundary between the photoreceptor inner and outer segments, which is also visible in standard-resolution OCT. The improved resolution of UHR OCT is especially advantageous in assessing photoreceptor morphology. CONCLUSIONS: Ultrahigh-resolution OCT enhances the visualization of intraretinal architectural morphology relative to standard-resolution OCT. Ultrahigh-resolution OCT images can provide a baseline for defining the interpretation of standard-resolution images, thus enhancing the clinical utility of standard OCT imaging. In addition, UHR OCT can provide additional information on macular disease morphology that promises to improve understanding of disease progression and management.

Ultrahigh-resolution optical coherence tomography in glaucoma.

OBJECTIVE: Optical coherence tomography (OCT) has been shown to be a valuable tool in glaucoma assessment. We investigated a new ultrahigh-resolution OCT (UHR-OCT) imaging system in glaucoma patients and compared the findings with those obtained by conventional-resolution OCT. DESIGN: Retrospective comparative case series. PARTICIPANTS: A normal subject and 4 glaucoma patients representing various stages of glaucomatous damage. TESTING: All participants were scanned with StratusOCT (axial resolution of approximately 10 mum) and UHR-OCT (axial resolution of approximately 3 microm) at the same visit. MAIN OUTCOME MEASURE: Comparison of OCT findings detected with StratusOCT and UHR-OCT. RESULTS: Ultrahigh-resolution OCT provides a detailed cross-sectional view of the scanned retinal area that allows differentiation between retinal layers. These UHR images were markedly better than those obtained by the conventional-resolution OCT. CONCLUSIONS: Ultrahigh-resolution OCT provides high-resolution images of the ocular posterior segment, which improves the ability to detect retinal abnormalities due to glaucoma.

Ultrahigh resolution optical coherence tomography in macular dystrophy.

PURPOSE: To visualize and investigate intraretinal changes in macular dystrophies with ultrahigh resolution optical coherence tomography (UHR OCT). DESIGN: Prospective observational case series. METHODS: setting: Department of Ophthalmology and Center for Biomedical Engineering and Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria. patients: Thirteen patients (23 eyes) with adult-onset foveomacular vitelliform dystrophy (AOFVD) and 14 patients (27 eyes) with Stargardt's disease (SD) or fundus flavimaculatus (FF). OBSERVATIONS: Imaging using a compact, new generation UHR OCT system, achieving considerably improved visualization of intraretinal layers, especially the photoreceptor layer. main outcome measures: UHR OCT tomograms visualizing intraretinal differences in morphology of AOFVD and SD/FF as location and extension of deposits and loss of photoreceptors. Central foveal thickness defined as distance between internal limiting membrane and photoreceptors/retinal pigment epithelium interface. RESULTS: Patients with AOFVD had a mostly intact photoreceptor layer, a central foveal thickness of 142 +/- 23 microm as well as subretinal deposits. Patients with SD generally had a diffuse degenerative change with a visible reduction in thickness of all intraretinal layers, resulting in a corresponding reduction of central foveal thickness (94 +/- 38 microm) and central loss of photoreceptors (PRs). Comparative central foveal thickness of patients with AOFVD and SD/FF was significantly different (P < .001). Patients with FF had pigment epithelial deposits and paracentral focal photoreceptor loss. CONCLUSIONS: UHR OCT is a clinically feasible tool for examining intraretinal changes, in particular photoreceptor atrophy in macular dystrophies and, therefore, has the potential to be an adequate imaging system for monitoring the course of disease.

Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair.

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.