Andre J. Witkin

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.

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.

Ultrahigh resolution optical coherence tomography in non‐exudative age related macular degeneration

Aim: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT). Methods: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of ∼3 μm axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed. Results: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT. Conclusion: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Microstructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical coherence tomography.

Background: Histopathological studies of acute multiple evanescent white dot syndrome (MEWDS) have not been reported because of the transient and benign nature of the disease. Ultrahigh resolution optical coherence tomography (UHR-OCT), capable of high resolution in vivo imaging, offers a unique opportunity to visualize retinal microstructure in the disease. Methods: UHR-OCT images of the maculae of five patients with MEWDS were obtained and analyzed. Diagnosis was based on clinical presentation, examination, visual field testing, and angiography. Results: UHR-OCT revealed disturbances in the photoreceptor inner/outer segment junction (IS/OS) in each of the five patients (six eyes) with MEWDS. In addition, thinning of the outer nuclear layer was seen in the case of recurrent MEWDS, suggesting that repeated episodes of MEWDS may result in photoreceptor atrophy. Conclusions: Subtle disruptions of the photoreceptor IS/OS are demonstrated in all eyes affected by MEWDS. UHR-OCT may be a useful adjunct to diagnosis and monitoring of MEWDS.

Vision Loss After Intravitreal Ocriplasmin: Correlation of Spectral-Domain Optical Coherence Tomography and Electroretinography

IMPORTANCE Clinical trials indicate that visual impairment is significantly greater in patients receiving ocriplasmin than placebo. The mechanism of this symptom has not been explained. We report a patient with persistent darkening of her vision after intravitreal ocriplasmin and describe ancillary testing findings that may yield insights into the effects of ocriplasmin and the cause of this symptom. OBSERVATIONS We describe a 71-year-old woman with symptomatic vitreomacular traction who received intravitreal ocriplasmin and experienced darkening of vision in dim illumination for 4 months, despite improvement in visual acuity and release of symptomatic vitreomacular traction. We demonstrate that disruption of photoreceptor inner segment-outer segment (ellipsoid) layer on SD-OCT and reduced ERG amplitudes correspond to the patients symptom of darkened vision. The ERG demonstrated a greater reduction in scotopic function compared with photopic function. CONCLUSIONS AND RELEVANCE On the basis of these findings, it is possible that ocriplasmin may have a diffuse enzymatic effect on photoreceptors or the retinal pigment epithelium that is not limited to areas of vitreomacular adhesion. The rod photoreceptors may be more susceptible than cone photoreceptors to the effects of ocriplasmin. Further work is needed to understand mechanisms of visual impairment after ocriplasmin.

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.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.

PURPOSE To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN Retrospective case series. SUBJECTS Eleven eyes of 6 patients from 6 different institutions. METHODS Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

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.

CHARACTERIZING THE EFFECT OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ON TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To use optical coherence tomography angiography (OCTA) to characterize the effects of anti-VEGF injections on treatment-naive choroidal neovascularization (CNV). Methods: From August 2014 to May 2015, treatment-naive eyes with CNV were scanned using a prototype OCTA system on a commercially available SD-OCT device (Optovue Inc, Fremont, CA). Optical coherence tomography angiography scans were obtained before anti-VEGF injection and at follow-up visits. The CNV area and greatest linear dimension (GLD) were measured along with the maximum retinal pigment epithelial detachment (RPED) height. Changes in subretinal and/or intraretinal fluid were also assessed. Results: Six eyes of six patients with treatment-naive CNV were included. Diagnoses included neovascular age-related macular degeneration, idiopathic polypoidal choroidal vasculopathy, CNV secondary to central serous chorioretinopathy and multifocal choroiditis, and macular telangiectasia Type 2 with subretinal neovascularization. After treatment, all patients with fluid on OCT initially showed a decrease in the amount of fluid. Five of six patients demonstrated decreases in CNV GLD and area with an average reduction of 23.6% and 29.8% respectively. Conclusion: Both CNV greatest linear dimension and area measured using OCTA decreased after anti-VEGF treatment in most patients. Optical coherence tomography angiography may be a useful tool for monitoring and quantifying the response of CNV to treatment.

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.