Optical Coherence Tomography Minimum Intensity as an Objective Measure for the Detection of Hydroxychloroquine Toxicity.

Purpose: As optical coherence tomography (OCT) minimum intensity (MI) analysis provides a quantitative assessment of changes in the outer nuclear layer (ONL), we evaluated the ability of OCT-MI analysis to detect hydroxychloroquine toxicity. Methods: Fifty-seven predominantly female participants (91.2% female; mean age, 55.7 ± 10.4 years; mean time on hydroxychloroquine, 15.0 ± 7.5 years) were enrolled in a case-control study and categorized into affected (i.e., with toxicity, n = 19) and unaffected (n = 38) groups using objective multifocal electroretinographic (mfERG) criteria. Spectral-domain OCT scans of the macula were analyzed and OCT-MI values quantitated for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A two-sample U-test and a cross-validation approach were used to assess the sensitivity and specificity of toxicity detection according to OCT-MI criteria. Results: The medians of the OCT-MI values in all nine of the ETDRS subfields were significantly elevated in the affected group relative to the unaffected group (P < 0.005 for all comparisons), with the largest difference found for the inner inferior subfield (P < 0.0001). The receiver operating characteristic analysis of median MI values of the inner inferior subfields showed high sensitivity and high specificity in the detection of toxicity with area under the curve = 0.99. Conclusions: Retinal changes secondary to hydroxychloroquine toxicity result in increased OCT reflectivity in the ONL that can be detected and quantitated using OCT-MI analysis. Analysis of OCT-MI values demonstrates high sensitivity and specificity for detecting the presence of hydroxychloroquine toxicity in this cohort and may contribute additionally to current screening practices.

Projection artifact removal improves visualization and quantitation of macular neovascularization imaged by optical coherence tomography angiography.

PURPOSE: To visualize and quantify the size and vessel density of macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) with a projection artifact removal algorithm. DESIGN: Multicenter, observational study. PARTICIPANTS: Subjects with MNV in at least one eye. METHODS: Patients were imaged using either a swept-source OCT angiography (SS-OCTA) prototype system or a spectral-domain OCT angiography (SD-OCTA) prototype system. The optical microangiography (OMAG) algorithm was used to generate the OCTA images. Projection artifacts from the overlying retinal circulation were removed from the OMAG OCTA images using a novel algorithm. Following removal of the projection artifacts from the OCTA images, we assessed the size and vascularity of the MNV. Concurrent fluorescein angiography (FA) and indocyanine green angiography (ICGA) images were used to validate the artifact-free OMAG images whenever available. MAIN OUTCOME MEASURES: Size and vascularity of MNV imaged with OCTA before and after the use of a projection-artifact removal algorithm. RESULTS: A total of 30 subjects (40 eyes) diagnosed with MNV were imaged. Five patients were imaged before and after intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Following the use of the projection artifact removal algorithm, we found improved visualization of the MNV. Lesion sizes and vascular densities were more easily measured on all the artifact-free OMAG images. In eyes treated with vascular endothelial growth factor inhibitors, vascular density was reduced in all five eyes after treatment, and in four eyes, the size of the MNV decreased. One of five patients showed a slight increase in lesion size, but a decrease in vascular density. CONCLUSIONS: OCTA imaging of MNV using the OMAG algorithm combined with removal of projection artifacts resulted in improved visualization and measurements of the neovascular lesions. OMAG with projection artifact removal should be useful for assessing the response of MNV to treatment using OCTA imaging.

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 µm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen.

PURPOSE: The ability to detect reticular pseudodrusen (RPD)/subretinal drusenoid deposits (SDDs) using 12×12-mm widefield en face swept-source optical coherence tomography (SS-OCT) imaging was compared with conventional multimodal imaging (color, fundus autofluorescence (FAF), and infrared reflectance [IR] imaging) in eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with nonexudative AMD were prospectively enrolled in an SS-OCT imaging study at the Bascom Palmer Eye Institute. METHODS: On the same day, all participants underwent color, FAF, and IR fundus imaging, as well as imaging with a prototype Zeiss 100 kHz SS-OCT instrument (Carl Zeiss Meditec Inc, Dublin, CA). Two masked graders assessed the presence, absence, or uncertainty of RPD/SDDs on conventional multimodal images and separately on 4 different SS-OCT en face images derived from the same volumetric dataset. The results from grading the conventional images and the SS-OCT en face images were compared. MAIN OUTCOME MEASURES: Agreement in the detection of RPD/SDDs using different imaging modalities. RESULTS: A total of 307 eyes (209 patients) were graded for the presence or absence of RPD/SDDs. The agreement between SS-OCT and multimodal imaging was 83%. The difference in RPD/SDD detection with either image modality was not statistically significant (P = 0.21). The sensitivity of SS-OCT in RPD/SDD detection was 83%, and when using conventional imaging, the sensitivity was 75%. When using SS-OCT imaging alone, 10% of RPD/SDD cases would be missed, and when using conventional imaging alone, 14% of RPD/SDD cases would be missed. The presence of RPD/SDD was confirmed retrospectively in 48 of 52 cases once the overall grading was unmasked and the graders reevaluated the conventional multimodal images and the widefield SS-OCT en face images. CONCLUSIONS: All 4 imaging modalities used together provided the best strategy for the detection of RPD/SDDs. However, when using widefield en face SS-OCT slab imaging alone, the detection of RPD/SDDs was at least as good as conventional imaging.

Optical Coherence Tomography Angiography of Asymptomatic Neovascularization in Intermediate Age-Related Macular Degeneration.

PURPOSE: To determine whether angiography with swept-source (SS) optical coherence tomography (OCT) identifies subclinical type 1 neovascularization in asymptomatic eyes with intermediate age-related macular degeneration (iAMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Patients with asymptomatic iAMD in one eye and neovascular age-related macular degeneration (AMD) in their fellow eye. METHODS: The patients underwent SS OCT angiography (OCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA), and the images from these 3 angiographic techniques were compared. MAIN OUTCOME MEASURES: Identification of subclinical type 1 neovascularization with SS OCTA in asymptomatic eyes with iAMD. RESULTS: Eleven consecutive patients with iAMD in one eye and neovascular AMD in their fellow eye were imaged with FA, ICGA, and SS OCTA between August 2014 and September 2015. Clinical examination of the 11 eyes revealed drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on routine OCT imaging. Ten of the 11 eyes had no evidence of leakage on FA and 1 eye had questionable fluorescein leakage. Indocyanine green angiography revealed the presence of central macular plaques in 3 of the 11 asymptomatic eyes with iAMD, and SS OCTA revealed unambiguous type 1 neovascularization corresponding to the plaques in all 3 eyes. Optical coherence tomography angiography did not identify neovascularization in the remaining 8 eyes. CONCLUSIONS: Swept-source OCTA identified type 1 neovascularization corresponding to ICGA plaques in asymptomatic eyes with iAMD. The ability of OCTA to provide noninvasive, fast, detailed, depth-resolved identification of nonexudative neovascular lesions in eyes with iAMD suggests the need for a new classification system that distinguishes between neovascular and nonneovascular iAMD.

SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF NEOVASCULAR MACULAR TELANGIECTASIA TYPE 2.

BACKGROUND/PURPOSE: To image subretinal neovascularization in proliferative macular telangiectasia Type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). METHODS: Patients with macular telangiectasia Type 2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1,050 nm swept-source OCT prototype system. The OMAG algorithm generated en face flow images from three retinal layers, and the region bounded by the outer retina and Bruch membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared with images from fluorescein angiography and indocyanine green angiography. RESULTS: Three eyes with neovascular macular telangiectasia Type 2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch membrane. Optical coherence tomography based microangiography images identified these abnormal vessels better than fluorescein angiography and were comparable to the images obtained using indocyanine green angiography. In all 3 cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the 2 cases with indocyanine green angiography imaging. In 1 case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, and the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. CONCLUSION: Optical coherence tomography based microangiography imaging provided detailed, depth-resolved information about subretinal neovascularization in macular telangiectasia Type 2 eyes demonstrating superiority to fluorescein angiography imaging, and similarities to indocyanine green angiography imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy.

Characterizing the Impact of Off-Axis Scan Acquisition on the Reproducibility of Total Retinal Thickness Measurements in SDOCT Volumes.

PURPOSE: Off-axis acquisition of spectral domain optical coherence tomography (SDOCT) images has been shown to increase total retinal thickness (TRT) measurements. We analyzed the reproducibility of TRT measurements obtained using either the retinal pigment epithelium (RPE) or Bruch's membrane as reference surfaces in off-axis scans intentionally acquired through multiple pupil positions. METHODS: Five volumetric SDOCT scans of the macula were obtained from one eye of 25 normal subjects. One scan was acquired through a central pupil position, while subsequent scans were acquired through four peripheral pupil positions. The internal limiting membrane, the RPE, and Bruch's membrane were segmented using automated approaches. These volumes were registered to each other and the TRT was evaluated in 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions. The reproducibility of the TRT obtained using the RPE was computed using the mean difference, coefficient of variation (CV), and the intraclass correlation coefficient (ICC), and compared to those obtained using Bruch's membrane as the reference surface. A secondary set of 1545 SDOCT scans was also analyzed in order to gauge the incidence of off-axis scans in a typical acquisition environment. RESULTS: The photoreceptor tips were dimmer in off-axis images, which affected the RPE segmentation. The overall mean TRT difference and CV obtained using the RPE were 7.04 ± 4.31 µm and 1.46%, respectively, whereas Bruch's membrane was 1.16 ± 1.00 µm and 0.32%, respectively. The ICCs at the subfoveal TRT were 0.982 and 0.999, respectively. Forty-one percent of the scans in the secondary set showed large tilts (> 6%). CONCLUSIONS: RPE segmentation is confounded by its proximity to the interdigitation zone, a structure strongly affected by the optical Stiles-Crawford effect. Bruch's membrane, however, is unaffected leading to a more robust segmentation that is less dependent upon pupil position. TRANSLATIONAL RELEVANCE: The way in which OCT images are acquired can independently affect the accuracy of automated retinal thickness measurements. Assessment of scan angle in a clinical dataset demonstrates that off-axis scans are common, which emphasizes the need for caution when relying on automated thickness parameters when this component of scan acquisition is not controlled for.

Widefield En Face Optical Coherence Tomography Imaging of Subretinal Drusenoid Deposits.

BACKGROUND AND OBJECTIVE: To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans. PATIENTS AND METHODS: Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SS-OCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 µm and positioned at distances up to 55 µm above the retinal pigment epithelium (RPE). A montage of 6 × 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 × 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images. RESULTS: A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-µm thick slab with boundaries from 35 to 55 µm above the RPE. CONCLUSION: Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future.

Effect of ranibizumab on high-speed indocyanine green angiography and minimum intensity projection optical coherence tomography findings in neovascular age-related macular degeneration.

PURPOSE: The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. METHODS: High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. RESULTS: After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. CONCLUSION: Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

Swept-source OCT angiography of macular telangiectasia type 2.

BACKGROUND AND OBJECTIVE: To evaluate the central macular microvascular network in patients with macular telangiectasia type 2 (MacTel2) using optical coherence tomography (OCT)-based microangiography (OMAG). PATIENTS AND METHODS: Prospective, observational study of patients with MacTel2 evaluated using a swept-source OCT (SS-OCT) prototype. OMAG was performed using a 3 mm × 3 mm central foveal raster scan. The algorithm segmented the retina into three layers. Microvascular distribution was depicted as en face images, and qualitative information was compared to fluorescein angiography (FA) images. RESULTS: OMAG detected abnormal microvasculature in all MacTel2 eyes, predominantly in the middle retinal layers with neovascularization in the outer retina. These vessels correlated well with the FA alterations. The abnormal temporal, juxtafoveal microvasculature in MacTel2 became apparent as the disease progressed and in later stages tended to extend circumferentially, with anastomotic vessels temporally. CONCLUSION: OMAG provided detailed, depth- resolved information about the perifoveal macular microvasculature in MacTel2. In most cases, images were better using OMAG than FA. The OMAG images demonstrated that most of the leakage seen on FA appeared to arise from the abnormal perifoveal microvasculature in the middle retinal layer.

OCT minimum intensity as a predictor of geographic atrophy enlargement.

PURPOSE: We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin. METHODS: The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-µm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins. RESULTS: A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity. CONCLUSIONS: The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. (ClinicalTrials.gov number, NCT00935883.).

Predicting the progression of geographic atrophy in age-related macular degeneration with SD-OCT en face imaging of the outer retina.

BACKGROUND AND OBJECTIVE: Spectral-domain optical coherence tomography (SD-OCT) en face imaging was used to measure the growth of geographic atrophy (GA) and identify baseline anatomic changes in the outer retina in eyes with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: In this prospective study, eyes were imaged using 200 × 200 and 512 × 128 A-scan raster patterns. Outer retinal anatomy was visualized using en face imaging of a 20-µm thick slab encompassing the inner segment/outer segment (IS/OS) band. RESULTS: En face SD-OCT imaging of the IS/OS region revealed a bilaterally symmetrical pattern of outer retinal disruption extending beyond the borders of GA that accurately predicted the progression of GA over 1 year in 13 of 30 eyes (43.3%). In the remaining cases, the area of disruption was much larger than the area of progression. CONCLUSION: En face imaging of the outer retina can predict the growth of GA in some eyes. Due to the bilateral symmetry of these findings, this imaging strategy may identify a genetic subset of patients in whom photoreceptor loss precedes the progression of GA. These areas with outer retinal disruption should be followed in clinical trials designed to test treatments for dry AMD.

Comparison of geographic atrophy measurements from the OCT fundus image and the sub-RPE slab image.

PURPOSE: To compare two different approaches to measuring areas of geographic atrophy (GA) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Fifty eyes with GA were imaged with an SD-OCT instrument. OCT fundus images and sub- retinal pigment epithelium (RPE) slab images were generated. Three graders manually drew the GA boundaries on both en face images. An automated algorithm was used to segment the GA boundaries from the sub-RPE slabs. RESULTS: The agreement between the three manual measurements on both OCT fundus images (ICC = .998) and sub-RPE slabs (ICC = .999) was excellent. Area measurements from OCT fundus images and sub-RPE slabs were highly correlated. The agreement between manual and automated measurements on the sub-RPE slabs was very good (ICC = .795). CONCLUSION: Both OCT fundus images and sub-RPE slab images proved useful for measuring GA in age-related macular degeneration. The automated algorithm typically provided useful measurements of GA area from the sub-RPE slabs.

Automated characterization of pigment epithelial detachment by optical coherence tomography.

PURPOSE: To assess the accuracy of automated classification of pigment epithelial detachments (PED) by using a software algorithm applied to spectral-domain optical coherence tomography (SD-OCT) scans. METHODS: HD-OCT (Cirrus; Carl Zeiss Meditec, Dublin, CA) volume scans (512 × 128) were retrospectively collected from 46 eyes of 33 patients with evidence of PED in the setting of age-related macular degeneration (AMD, n = 28) or central serous chorioretinopathy (CSCR, n = 5). In these eyes, 168 PEDs were automatically detected with a system-associated tool (Cirrus HD-OCT RPE Elevation Analysis; Carl Zeiss Meditec). Two independent, certified Doheny Image Reading Center (DIRC) OCT graders classified these PEDs into three categories--serous, drusenoid, or fibrovascular--via inspection of the B-scans. Manual classification results served as the gold standard for comparisons with automated classification. For automated classification, interindividual variation in intensities was normalized in all images. Individual A-scans within the detected PEDs were then automatically classified into one of three categories based on the mean internal intensity and the standard deviation of the internal intensity: mean intensity <30 (serous type); mean intensity ≥30 but <60 or mean intensity ≥30 and SD ≥30 (fibrovascular type); or mean intensity ≥60 and SD < 30 (drusenoid type). Individual PEDs were then automatically classified into the same three categories based on the predominant type of A-scan within the PED. For mixed PEDs (many A-scans of each type), a risk index for neovascularization was computed based on the percentage of fibrovascular A-scans. In addition, a confidence index was computed for each PED based on its mathematical distance from the PED category boundaries. RESULTS: Among the 168 PEDs, the DIRC graders classified 16 as serous, 88 as fibrovascular, and 64 as drusenoid PEDs. The automated algorithm classified 14 as serous, 96 as fibrovascular, and 58 as drusenoid PEDs. The sensitivity and specificity values for automated classification according to type of PED were 88% and 100% for serous, 76% and 64% for fibrovascular, and 58% and 81% for drusenoid, respectively. CONCLUSIONS: Automated classification of PEDs using internal reflectivity characteristics appears to be sensitive for detecting serous and fibrovascular PEDs. Automated classification and quantification of PEDs may be a useful tool in future studies for stratifying PEDs according to risk and possibly predicting the risk of advanced AMD.

Quantitative assessment of photoreceptor recovery in atypical multiple evanescent white dot syndrome.

Multiple evanescent white dot syndrome (MEWDS) is part of a spectrum of disease entities known as acute zonal occult outer retinopathy-complex that share photoreceptor disruption as a cardinal feature. Optical coherence tomography (OCT) allows for qualitative assessment of the integrity of the photoreceptor layer via examination of the junction between the photoreceptor inner and outer segments. A patient with atypical MEWDS who demonstrated disruption of the inner segment/outer segment junction during the acute phase of the disease is described. The change in photoreceptor architecture and abnormalities on fundus autofluorescence imaging and microperimetry were restored to normal following resolution of the disease. Using a novel OCT-based method of quantitatively measuring photoreceptor outer segment length, the authors show that photoreceptor outer segment length appears decreased acutely with restoration to normal following disease resolution. OCT can assess photoreceptor recovery, both qualitatively and quantitatively, in patients with MEWDS features.

Comparing retinal thickness measurements from Cirrus spectral domain- and Stratus time domain-optical coherence tomography.

PURPOSE: The purpose of this study was to compare retinal measurements obtained using spectral domain-optical coherence tomography with measurements obtained using time domain-optical coherence tomography. METHODS: Three hundred and seventy subjects were recruited at three university-based and one community-based retina practice for a cross-sectional observational study. For each subject, one eye was enrolled as the study eye. A Stratus Fast Macular scan was performed, and a Cirrus 200 x 200 Macular Cube scan was performed. Both instruments segment the acquired images to generate retinal thickness values and report averages measured in nine subfields defined by the Early Treatment Diabetic Retinopathy Study. These average values were compared with each other quantitatively using linear regression and Bland-Altman plots. RESULTS: Of the recruited subjects, 283 had acceptable images taken on the same day with both the Cirrus and Stratus devices. Mean differences between the instruments were noted in all subfields for all disease categories and ranged from 29 microm (outer superior subfield) to 54 microm (central subfield). CONCLUSION: Differences between time domain and spectral domain measurements of retinal thickness depend on pathology and location. Comparisons across instruments should be made with caution.

Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema.

PURPOSE: The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. METHODS: Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. RESULTS: Mean retinal thickness and PROS length were 298 mum to 381 microm and 30 microm to 32 mum, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. CONCLUSION: Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects.