Mehreen Adhi

Optical coherence tomography – current and future applications

Purpose of review Optical coherence tomography (OCT) has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high-resolution, cross-sectional images of the retina, retinal nerve fiber layer and the optic nerve head. This review discusses the present applications of the commercially available spectral-domain OCT (SD-OCT) systems in the diagnosis and management of retinal diseases, with particular emphasis on choroidal imaging. Future directions of OCT technology and their potential clinical uses are discussed. Recent findings Analysis of the choroidal thickness in healthy eyes and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies has been successfully achieved using SD-OCT devices with software improvements. Future OCT innovations such as longer-wavelength OCT systems including the swept-source technology, along with Doppler OCT and en-face imaging, may improve the detection of subtle microstructural changes in chorioretinal diseases by improving imaging of the choroid. Summary Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the posterior segment of the eye. Further improvements in both hardware and software technologies should further advance the clinicians ability to assess and manage chorioretinal diseases.

Spectral-Domain Optical Coherence Tomography Angiography of Choroidal Neovascularization

PURPOSE To describe the characteristics as well as the sensitivity and specificity of detection of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) using spectral-domain optical coherence tomography. DESIGN Observational, retrospective study. PARTICIPANTS Seventy-two eyes of 61 subjects (48 eyes of 43 subjects with CNV, 24 eyes of 18 subjects without CNV). METHODS Patients imaged using the prototype AngioVue OCTA system (Optovue, Inc, Fremont, CA) between August 2014 and October 2014 at New England Eye Center were assessed. Patients in whom CNV was identified on OCTA were evaluated to define characteristics of CNV on OCTA: size using greatest linear dimension (small, <1 mm; medium, 1-2 mm; large, >2 mm), appearance (well-circumscribed, poorly circumscribed), and presence of subretinal and intraretinal fluid. Concurrently, an overlapping second cohort of patients who underwent same-day OCTA and fluorescein angiography (FA) for suspected CNV was evaluated to estimate sensitivity and specificity of OCTA in detecting CNV using FA as ground truth. MAIN OUTCOME MEASURES Choroidal neovascularization appearance, CNV size, and presence of subretinal and intraretinal fluid. RESULTS In 48 eyes, CNV was visualized on OCTA. Thirty-one eyes had CNV associated with neovascular age-related macular degeneration. Size of CNV was small in 23% (7/31), medium in 42% (13/31), and large in 35% (11/31). Poorly circumscribed vessels, subretinal fluid, and intraretinal fluid each were seen in 71% (22/31). Seven eyes had CNV associated with central serous chorioretinopathy. Size of CNV was small in 71% (5/7) and large in 29% (2/7). Seventy-one percent (5/7) had well-circumscribed vessels, 86% (6/7) had subretinal fluid, and 14% (1/7) had intraretinal fluid. Thirty eyes with OCTA and same-day FA were evaluated to determine sensitivity and specificity of CNV detection on OCTA. Sensitivity was 50% (4/8) and specificity was 91% (20/22). CONCLUSIONS Using OCTA allows the clinician to visualize CNV noninvasively and may provide a method for identifying and guiding treatment of CNV. The specificity of CNV detection on OCTA compared with FA seems to be high. Future studies with larger sample sizes are needed to elaborate better on the sensitivity and specificity of CNV detection and to illustrate clinical usefulness.

Ultrahigh-Speed Swept-Source OCT Angiography in Exudative AMD

BACKGROUND AND OBJECTIVE To investigate the potential of ultrahigh-speed swept-source optical coherence tomography angiography (OCTA) to visualize retinal and choroidal vascular changes in patients with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS Observational, prospective cross-sectional study. An ultrahigh-speed swept-source prototype was used to perform OCTA of the retinal and choriocapillaris microvasculature in 63 eyes of 32 healthy controls and 19 eyes of 15 patients with exudative AMD. MAIN OUTCOME MEASURE qualitative comparison of the retinal and choriocapillaris microvasculature in the two groups. RESULTS Choroidal neovascularization (CNV) was clearly visualized in 16 of the 19 eyes with exudative AMD, located above regions of severe choriocapillaris alteration. In 14 of these eyes, the CNV lesions were surrounded by regions of choriocapillaris alteration. CONCLUSION OCTA may offer noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, which may assist in diagnosis and monitoring.

EN FACE ENHANCED-DEPTH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY FEATURES OF CHRONIC CENTRAL SEROUS CHORIORETINOPATHY

OBJECTIVE To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR) using a high-speed, enhanced-depth swept-source optical coherence tomography (SS-OCT) prototype. DESIGN Consecutive patients with chronic CSCR were prospectively examined with SS-OCT. PARTICIPANTS Fifteen eyes of 13 patients. METHODS Three-dimensional 6×6 mm macular cube raster scans were obtained with SS-OCT operating at 1050 nm wavelength and 100000 A-lines/sec with 6 μm axial resolution. Segmentation of the RPE generated a reference surface; en face SS-OCT images of the RPE and choroid were extracted at varying depths every 3.5 μm (1 pixel). Abnormal features were characterized by systematic analysis of multimodal fundus imaging, including color photographs, fundus autofluorescence, fluorescein angiography, and indocyanine-green angiography (ICGA). MAIN OUTCOME MEASURES En face SS-OCT morphology of the RPE and individual choroidal layers. RESULTS En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At the level of Sattlers layer, en face SS-OCT documented focal choroidal dilation in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At the level of Hallers layer, these same features were observed in 3 of 15 eyes (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these choroidal vascular abnormalities were seen just below areas of RPE abnormalities. In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS-OCT features corresponded to the neovascular lesions. CONCLUSIONS High-speed, enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of pathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems to be a useful tool in the identification of CNV without the use of angiography. This in vivo documentation of the RPE and choroidal vasculature at variable depths may help elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronic CSCR.

Ultrahigh-Speed, Swept-Source Optical Coherence Tomography Angiography in Nonexudative Age-Related Macular Degeneration with Geographic Atrophy

PURPOSE To investigate ultrahigh-speed, swept-source optical coherence tomography (SSOCT) angiography for visualizing vascular changes in eyes with nonexudative age-related macular degeneration (AMD) with geographic atrophy (GA). DESIGN Observational, prospective, cross-sectional study. PARTICIPANTS A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA. METHODS A 1050-nm, 400-kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris (CC) vasculatures in normal subjects and patients with nonexudative AMD with GA. Optical coherence tomography angiography using variable interscan time analysis (VISTA) was performed to assess CC alteration and differentiate varying degrees of CC flow impairment. MAIN OUTCOME MEASURES Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA. RESULTS In all 12 eyes with GA, OCTA showed pronounced CC flow impairment within the region of GA. In 10 of the 12 eyes with GA, OCTA with VISTA showed milder CC flow impairment extending beyond the margin of GA. Of the 5 eyes exhibiting foveal-sparing GA, OCTA showed CC flow within the region of foveal sparing in 4 of the eyes. CONCLUSIONS The ability of ultrahigh-speed, swept-source OCTA to noninvasively visualize alterations in the retinal and CC vasculatures makes it a promising tool for assessing nonexudative AMD with GA. Optical coherence tomography angiography using VISTA can distinguish varying degrees of CC alteration and flow impairment and may be useful for elucidating disease pathogenesis, progression, and response to therapy.

Analysis of Morphological Features and Vascular Layers of Choroid in Diabetic Retinopathy Using Spectral-Domain Optical Coherence Tomography

IMPORTANCE Diabetic retinopathy (DR) is characterized by microaneurysms, capillary nonperfusion, and ischemia within the retina, ultimately leading to neovascularization and/or macular edema. Evidence suggests that choroidal angiopathy may coexist with retinal vascular damage. Recent advances in spectral-domain optical coherence tomography (SD-OCT) permit an efficient visualization of the choroid. OBJECTIVE To analyze the morphological features and vascular layers of the choroid in patients with DR using SD-OCT. DESIGN A cross-sectional retrospective review identified patients with DR and healthy (control) subjects who underwent 1-line raster scanning from February 1, 2010, through June 30, 2012. Patients were classified into the following 3 groups: nonproliferative DR without macular edema (9 eyes), proliferative DR without macular edema (PDR) (10 eyes), and diabetic macular edema (DME) (14 eyes). Two independent raters experienced in analyzing OCT images evaluated the morphological features and vasculature of the choroid. SETTING New England Eye Center. PARTICIPANTS Thirty-three eyes of 33 patients with DR and 24 eyes of 24 controls. EXPOSURE Diabetic retinopathy. MAIN OUTCOME AND MEASURE Choroidal morphological features and vasculature analysis. RESULTS The choroidoscleral interface had an irregular contour in 8 of 9 eyes with nonproliferative DR (89%), 9 of 10 eyes with PDR (90%), and 13 of 14 eyes with DME (93%) compared with 0 of 24 controls. The thickest point of the choroid was displaced from under the fovea, and focal choroidal thinning was observed in eyes with DR. Mean subfoveal choroidal thickness and mean subfoveal medium choroidal vessel layer and choriocapillaris layer thickness were significantly reduced in eyes with PDR (P < .05) and DME (P < .05) compared with controls. CONCLUSIONS AND RELEVANCE Choroidal morphological features are altered in patients with moderate to severe DR. The subfoveal choroidal thickness and the subfoveal medium choroidal vessel layer and choriocapillaris layer thicknesses are significantly reduced in patients with PDR and DME. To our knowledge, this is the first study to analyze the morphological features and vasculature of the choroid in DR using SD-OCT. These findings may be clinically useful in predicting the progression of DR.

Detection Of Microvascular Changes In Eyes Of Patients With Diabetes But Not Clinical Diabetic Retinopathy Using Optical Coherence Tomography Angiography

Purpose: To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. Methods: Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. Results: Foveal avascular zone size measured 0.348 mm2 (0.1085–0.671) in diabetic eyes and 0.288 mm2 (0.07–0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. Conclusion: Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made.

Association of Choroidal Neovascularization and Central Serous Chorioretinopathy With Optical Coherence Tomography Angiography

IMPORTANCE Choroidal neovascularization (CNV) is a major cause of vision loss in chronic central serous chorioretinopathy (CSCR). Detecting CNV using fluorescein angiography (FA) may be challenging owing to the coexistence of features related to the primary diagnosis of CSCR. Optical coherence tomography angiography (OCTA) allows noninvasive visualization of retinal and choroidal vasculature via motion contrast and may contribute to the unequivocal diagnosis of CNV in this population. OBJECTIVE To evaluate the sensitivity of spectral-domain OCTA in detecting CNV associated with chronic CSCR. DESIGN, SETTING, AND PARTICIPANTS Observational cross-sectional study including 23 patients (27 eyes) who presented at the New England Eye Center between August 1, 2014, and November 30, 2014, with suspected CNV complicating chronic CSCR and underwent standard assessment for CNV diagnosis, including FA imaging. Participants were prospectively recruited to receive imaging tests using prototype OCTA software on a commercially available spectral-domain OCT. Orthogonal registration and the merging of 2 consecutive image sets were used to obtain 3 × 3-mm and 6 × 6-mm OCT angiograms centered at the macula. Two independent readers masked to other imaging findings performed a qualitative analysis on OCTA depictions of vascular flow representing CNV and the morphologic appearance of CNV. MAIN OUTCOMES AND MEASURES Choroidal neovascularization location as well as retinal pigment epithelial detachment internal reflectivity and the presence of subretinal and intraretinal fluid. Sensitivity and specificity of OCTA in detecting CNV were estimated using FA as the standard examination reference. RESULTS Choroidal neovascularization was diagnosed in 8 of 27 eyes (30%) based on FA imaging analysis. Optical coherence tomography angiography and corresponding OCT B-scans detected 100% (8 of 8) of these CNV lesions and correctly excluded 100% (19 of 19) of eyes with CSCR without CNV. Sensitivity was 100% (95% CI, 0.62-1) and specificity was 100% (95% CI, 0.82-1). Morphologic appearance, location, and position of the CNV relative to the retinal pigment epithelium and Bruch membrane were described using OCTA that combined flow and structural information. CONCLUSIONS AND RELEVANCE This study suggests that OCT alone (OCTA and coregistered OCT B-scans) features sensitivity and specificity comparable with FA for the detection of CNV in eyes with chronic CSCR.

Choroidal analysis in healthy eyes using swept-source optical coherence tomography compared to spectral domain optical coherence tomography.

PURPOSE To compare analyses of choroidal thickness and volume in healthy eyes measured concurrently with prototype long-wavelength swept-source optical coherence tomography (OCT) and commercially available spectral-domain optical coherence tomography (OCT) with and without enhanced depth imaging (EDI). DESIGN Prospective cross sectional study. METHODS The study included 19 healthy subjects (19 eyes), who were prospectively recruited to undergo 2 consecutive imaging sessions on the same randomly selected eye using spectral domain OCT and a prototype long-wavelength swept-source OCT. On spectral domain OCT, 2 line scans, 1 with and 1 without EDI, and 1 volumetric scan were obtained. On swept-source OCT, 1 line scan and 1 volumetric scan were obtained. Scan patterns on swept-source OCT were created to simulate those available on Cirrus HD-OCT to keep the time of image acquisition constant. Swept-source OCT volumetric scans were motion corrected using a novel registration algorithm. Choroidal thickness and volume were analyzed. RESULTS The choroidoscleral interface was clearly visualized in 19/19 (100%) of eyes imaged by swept-source OCT, compared to 14/19 (73.6%) and 13/19 (68.4%) eyes imaged by spectral domain OCT, with and without EDI, respectively. There was no significant difference in choroidal thickness measurements on the line scans obtained on either system (P = 0.10). Choroidal volume could not be assessed on volumetric scans from spectral domain OCT. Mean choroidal volume from swept-source OCT volumetric scans was 11.77 ± 3.13 mm(3) (6.43 mm(3)-17.15 mm(3)). CONCLUSION This is the first study that compares simultaneously a prototype long-wavelength swept-source OCT to a commercially available spectral domain OCT for a detailed analysis of choroid in healthy eyes. Swept-source OCT shows potential for better choroidal analysis. Studies using swept-source OCT in diseased eyes will further define this new technologys utility in chorioretinal diseases.

Select Features of Diabetic Retinopathy on Swept-Source Optical Coherence Tomographic Angiography Compared With Fluorescein Angiography and Normal Eyes

IMPORTANCE Optical coherence tomographic angiography (OCTA) is a recently developed noninvasive imaging technique that can visualize the retinal and choroidal microvasculature without the injection of exogenous dyes. OBJECTIVE To evaluate the potential clinical utility of OCTA using a prototype swept-source OCT (SS-OCT) device and compare it with fluorescein angiography (FA) for analysis of the retinal microvasculature in diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Prospective, observational cross-sectional study conducted at a tertiary care academic retina practice from November 2013 through November 2014. A cohort of diabetic and normal control eyes were imaged with a prototype SS-OCT system. The stage of diabetic retinopathy was determined by clinical examination. Imaging was performed using angiographic 3 × 3-mm and 6 × 6-mm SS-OCT scans to generate 3-dimensional en-face OCT angiograms for each eye. Two trained Boston Image Reading Center readers reviewed and graded FA and OCTA images independently. MAIN OUTCOMES AND MEASURES The size of the foveal nonflow zone and the perifoveal intercapillary area on OCTA were measured in both normal and diabetic eyes using Boston Image Reading Center image analysis software. RESULTS The study included 30 patients with diabetes (mean [SD] age, 55.7 [10] years) and 6 control individuals (mean [SD] age, 55.1 [6.4] years). A total of 43 diabetic and 11 normal control eyes were evaluated with OCTA. Fluorescein angiography was performed in 17 of 43 diabetic eyes within 8 weeks of the OCTA. Optical coherence tomographic angiography was able to identify a mean (SD) of 6.4 (4.0) microaneurysms (95% CI, 4.4-8.5), while FA identified a mean (SD) of 10 (6.9) microaneurysms (95% CI, 6.4-13.5). The exact intraretinal depth of microaneurysms on OCTA was localized in all cases (100%). The sensitivity of OCTA in detecting microaneuryms when compared with FA was 85% (95% CI, 53-97), while the specificity was 75% (95% CI, 21-98). The positive predictive value and the negative predictive value were 91% (95% CI, 59-99) and 60% (95% CI, 17-92), respectively. CONCLUSIONS AND RELEVANCE Optical coherence tomographic angiography enables noninvasive visualization of macular microvascular pathology in eyes with diabetic retinopathy. It identified fewer microaneurysms than FA, but located their exact intraretinal depth. Optical coherence tomographic angiography also allowed the precise and reproducible delineation of the foveal nonflow zone and perifoveal intercapillary area. Evaluation of OCTA may be of clinical utility in the evaluation and grading of diabetic eye disease.