Nadia K. Waheed

IMAGE ARTIFACTS IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe image artifacts of optical coherence tomography (OCT) angiography and their underlying causative mechanisms. To establish a common vocabulary for the artifacts observed. Methods: The methods by which OCT angiography images are acquired, generated, and displayed are reviewed as are the mechanisms by which each or all of these methods can produce extraneous image information. A common set of terminology is proposed and used. Results: Optical coherence tomography angiography uses motion contrast to image blood flow and thereby images the vasculature without the need for a contrast agent. Artifacts are very common and can arise from the OCT image acquisition, intrinsic characteristics of the eye, eye motion, image processing, and display strategies. Optical coherence tomography image acquisition for angiography takes more time than simple structural scans and necessitates trade-offs in flow resolution, scan quality, and speed. An important set of artifacts are projection artifacts in which images of blood vessels seem at erroneous locations. Image processing used for OCT angiography can alter vascular appearance through segmentation defects, and because of image display strategies can give false impressions of the density and location of vessels. Eye motion leads to discontinuities in displayed data. Optical coherence tomography angiography artifacts can be detected by interactive evaluation of the images. Conclusion: Image artifacts are common and can lead to incorrect interpretations of OCT angiography images. Because of the quantity of data available and the potential for artifacts, physician interaction in viewing the image data will be required, much like what happens in modern radiology practice.

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PURPOSE To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. DESIGN Retrospective noncomparative interventional case series. PARTICIPANTS All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. METHODS Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. MAIN OUTCOME MEASURES Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. RESULTS A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. CONCLUSIONS Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

A review of optical coherence tomography angiography (OCTA)

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging technique that generates volumetric angiography images in a matter of seconds. This is a nascent technology with a potential wide applicability for retinal vascular disease. At present, level 1 evidence of the technology’s clinical applications doesn’t exist. In this paper, we introduce the technology, review the available English language publications regarding OCTA, and compare it with the current angiographic gold standards, fluorescein angiography (FA) and indocyanine green angiography (ICGA). Finally we summarize its potential application to retinal vascular diseases. OCTA is quick and non-invasive, and provides volumetric data with the clinical capability of specifically localizing and delineating pathology along with the ability to show both structural and blood flow information in tandem. Its current limitations include a relatively small field of view, inability to show leakage, and proclivity for image artifact due to patient movement/blinking. Published studies hint at OCTA’s potential efficacy in the evaluation of common ophthalmologic diseases such age related macular degeneration (AMD), diabetic retinopathy, artery and vein occlusions, and glaucoma. OCTA can detect changes in choroidal blood vessel flow and can elucidate the presence of choroidal neovascularization (CNV) in a variety of conditions but especially in AMD. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) in diabetic eyes and detection of subtle microvascular abnormalities in diabetic and vascular occlusive eyes. Optic disc perfusion in glaucomatous eyes is notable as well on OCTA. Further studies are needed to more definitively determine OCTA’s utility in the clinical setting and to establish if this technology may offer a non-invasive option of visualizing the retinal vasculature in detail.

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.

Visual outcome in herpes simplex virus and varicella zoster virus uveitis: A clinical evaluation and comparison

PURPOSE To compare clinical characteristics and outcomes in patients with uveitis caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). DESIGN Retrospective comparative study. PARTICIPANTS Forty patients with HSV uveitis and 24 patients with VZV uveitis. METHODS A retrospective study of 40 patients with HSV and 24 patients with VZV uveitis was performed. The patients were followed between May 1987 and September 1999 (median follow-up time, 46 months). The diagnosis of HSV uveitis was made clinically and serologically, and the diagnosis of VZV uveitis was made clinically. MAIN OUTCOME MEASURES Clinical presentation of the disease, ocular complications, visual acuity, surgical and medical treatments needed. RESULTS Both populations were comparable for gender and age at disease onset. The course of the disease tended to be remitting and recurrent in HSV patients and chronic in VZV patients (P = 0.046). The most frequent ocular complication in both groups was secondary glaucoma (54% HSV, 38% VZV). Twenty-five percent of VZV patients developed posterior pole complications (cystoid macular edema, epiretinal membrane, papillitis, retinal fibrosis, and detachment) compared with 8% of HSV patients (P = 0.069). Treatment modalities selected were generally similar in the two groups, although periocular and systemic steroids were required more frequently in HSV patients (60% versus 25%; P = 0.01). Surgical procedures were required with similar frequency in both populations. The percentage of eyes that were legally blind at end of follow-up was also comparable (HSV, 20%; VZV, 21%). The visual outcome was similar in the studied populations. CONCLUSIONS This study represents the only direct comparison of HSV and VZV uveitis patients reported in the literature. HSV patients were more likely to be treated with periocular and systemic steroids, and VZV patients were more likely to develop posterior pole complications (a finding of borderline significance). Other parameters evaluated in this study were not statistically different in the two patient groups.