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Research Letter |

Sequential Optical Coherence Tomographic Angiography for Diagnosis and Treatment of Choroidal Neovascularization in Multifocal Choroiditis FREE

Caroline R. Baumal, MD1,2; Talisa E. de Carlo, BA1,2,3,4; Nadia K. Waheed, MD, MPH1,2; David A. Salz, MD1,2; Andre J. Witkin, MD1,2; Jay S. Duker, MD1,2
[+] Author Affiliations
1New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts
2Vitreoretinal Service, Tufts Medical Center, Tufts University, Boston, Massachusetts
3Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge
4Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge
JAMA Ophthalmol. 2015;133(9):1087-1090. doi:10.1001/jamaophthalmol.2015.1946.
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Published online

Accurate diagnosis of choroidal neovascularization (CNV) is critical to ensure timely anti–vascular endothelial growth factor therapy and preclude loss of visual acuity. Dye-based angiography is the gold standard for CNV diagnosis; however, it is invasive, is associated with risk of allergy, and may be limited by availability. Optical coherence tomography (OCT) angiography (OCTA) is a noninvasive, non–dye-based modality that generates en face images (OCT angiograms) of retinal and choroidal vascular layers.14 This is one of the first reports, to our knowledge, describing the clinical utility of OCTA to diagnose CNV in multifocal choroiditis where dye-based angiography was equivocal, then using sequential OCTA imaging to evaluate response to anti–vascular endothelial growth factor therapy.

A woman in her early 40s presented with acute vision loss in her left eye of 2 days’ duration. Her medical and travel histories were noncontributory. She was a glaucoma suspect based on optic nerve appearance. Best-corrected visual acuity was 20/20 OD and 20/40 OS. The right eye was normal with the exception of mild peripapillary atrophy and a cup-disc ratio of 0.7. In the left eye, there was mild 1+ cellular reaction in the anterior chamber and vitreous. There was a mildly elevated, hypopigmented deep chorioretinal lesion in the left fovea (Figure 1A) without associated fluid, hemorrhage, or exudate and scattered, small punctate and linear yellow deep choroidal lesions peripherally. Fluorescein angiography demonstrated early hyperfluorescence and late staining of the chorioretinal spots and staining of peripheral retinal veins (Figure 1B-D). Indocyanine green angiography revealed peripheral hypofluorescent spots and a pinpoint dot of late hyperfluorescence in the fovea (Figure 1E and F). Conventional spectral-domain OCT (Cirrus; Carl Zeiss Meditec) demonstrated an elevated foveal lesion beneath the retinal pigment epithelium with thickening and loss of distinct margins of the overlying ellipsoid and interdigitation bands but no fluid (Figure 2A). Multifocal choroiditis was diagnosed based on clinical and angiographic findings. Systemic testing results including the Venereal Disease Research Laboratory test, lysozyme, angiotensin-converting enzyme, purified protein derivative, and chest radiography were normal.

Place holder to copy figure label and caption
Figure 1.
Conventional Imaging of Choroidal Neovascularization

A, Fundus photograph of the chorioretinal lesion lacking hemorrhage or fluid. B-D, Early-phase hyperfluorescence of the lesion at 20 seconds (B), staining at 1 minute (C), and hyperfluorescent peripheral spots at 5 minutes (D) on fluorescein angiography. E and F, Hypofluorescence of the lesion at 1 minute (E) and pinpoint late hyperfluorescence at 10 minutes (F) on indocyanine green angiography.

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Figure 2.
Optical Coherence Tomography (OCT) and Sequential OCT Angiography (OCTA) of Choroidal Neovascularization

A-C, Cirrus OCT (A) and en face OCTA (B) revealed choroidal neovascularization, with subretinal fluid (arrowhead) present on Optovue B-scan (C). D-F, One week following the first treatment with bevacizumab, choroidal neovascularization was resolving on Cirrus OCT (D) and OCTA (E and F), with trace fluid (arrowhead in F). G and H, Four weeks following the first treatment with bevacizumab, OCTA showed decreased size and vascularity in choroidal neovascularization (arrowhead in G). I and J, Four weeks following the second treatment with bevacizumab, choroidal neovascularization (arrowhead in I) was barely visible on OCTA. C, F, H, and J, En face OCTA segmentation of the outer retina images is shown between the outer aspect of the inner nuclear layer (green line) and Bruch’s membrane (red line).

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The foveal lesion was clinically suspect for CNV; however, this was not conclusive after dye-based angiography and spectral-domain OCT. Retinal vascular imaging with the prototype AngioVue OCTA software on the commercially available Avanti spectral-domain OCT device (Optovue) was performed. The 3 × 3-mm OCT angiogram demonstrated a lacy network of vessels in the outer retina scan, confirming the presence of CNV as this location is devoid of vessels in healthy eyes (Figure 2B). One week after treatment with intravitreal bevacizumab (1.25 mg/0.05 mL), OCTA revealed reduction in size and density of the CNV complex (Figure 2E and F). Sequential OCTA following the first (Figure 2G and H) and second (Figure 2I and J) treatments with bevacizumab revealed progressive, near-complete resolution of flow through the CNV. The lesion appeared inactive clinically without leakage on fluorescein angiography after the second treatment with bevacizumab. The patient has subsequently been observed without recurrence for 5 months with resolved symptoms and visual acuity of 20/25 OS.

Diagnosis of CNV may be challenging if typical features are not apparent and angiographic signs are equivocal. This may be more likely in eyes with early CNV or secondary to causes other than age-related maculopathy such as myopia or multifocal choroiditis.5 The use of OCTA enables noncontact imaging of retinal and choroidal vasculature based on motion contrast via mapping erythrocyte movement over time by comparing sequential OCT B-scans in a given cross section.1,3,4 The OCT angiogram and corresponding OCT B-scans are coregistered to enable simultaneous imaging of blood flow with structural features.3,4 While conventional fluorescein angiography provides dynamic retinal blood flow images, OCTA delivers static information by delineating the vasculature features, including size of the abnormal vasculature.6 This case highlights the potential utility of OCTA to characterize CNV size and pattern and to demonstrate reduction of size and density of flow through CNV after anti–vascular endothelial growth factor treatment.

Corresponding Author: Caroline R. Baumal, MD, New England Eye Center, Tufts University School of Medicine, 800 Washington St, Box 450, Boston, MA 02111 (cbaumal@gmail.com).

Published Online: June 25, 2015. doi:10.1001/jamaophthalmol.2015.1946.

Author Contributions: Dr Baumal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Baumal, de Carlo, Waheed, Witkin, Duker.

Acquisition, analysis, or interpretation of data: de Carlo, Salz, Witkin.

Drafting of the manuscript: Baumal, Witkin.

Critical revision of the manuscript for important intellectual content: de Carlo, Waheed, Salz, Witkin, Duker.

Administrative, technical, or material support: Salz, Witkin, Duker.

Study supervision: Baumal, Waheed, Salz, Witkin, Duker.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Baumal reported serving as a consultant for Allergan and receiving a travel grant from Optovue. Dr Waheed reported serving as a consultant for Iconic Therapeutics; serving on the speakers bureau for Thrombogenics; and receiving research support from Carl Zeiss Meditec. Dr Duker reported serving as a consultant for and receiving research support from Carl Zeiss Meditec and Optovue. No other disclosures were reported.

Funding/Support: This work was supported in part by an unrestricted grant to the New England Eye Center, Tufts University School of Medicine from Research to Prevent Blindness and by the Massachusetts Lions Club.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This article was presented in part at the Atlantic Coast Retina Club 2015 Meeting; January 9, 2015; Boston, Massachusetts.

Jia  Y, Bailey  ST, Wilson  DJ,  et al.  Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014;121(7):1435-1444.
PubMed   |  Link to Article
Spaide  RF, Klancnik  JM  Jr, Cooney  MJ.  Retinal vascular layers in macular telangiectasia type 2 imaged by optical coherence tomographic angiography. JAMA Ophthalmol. 2015;133(1):66-73.
PubMed   |  Link to Article
Spaide  RF, Klancnik  JM  Jr, Cooney  MJ.  Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50.
PubMed   |  Link to Article
de Carlo  TE, Bonini Filho  MA, Chin  AT,  et al.  Spectral domain optical coherence tomography angiography (OCTA) of choroidal neovascularization [published online March 17, 2015]. Ophthalmology. doi:10.1016/j.ophtha.2015.01.029.
Kotsolis  AI, Killian  FA, Ladas  ID, Yannuzzi  LA.  Fluorescein angiography and optical coherence tomography concordance for choroidal neovascularisation in multifocal choroiditis. Br J Ophthalmol. 2010;94(11):1506-1508.
PubMed   |  Link to Article
Moult  E, Choi  W, Waheed  NK,  et al.  Ultrahigh-speed swept-source OCT angiography in exudative AMD. Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):496-505.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 2.
Optical Coherence Tomography (OCT) and Sequential OCT Angiography (OCTA) of Choroidal Neovascularization

A-C, Cirrus OCT (A) and en face OCTA (B) revealed choroidal neovascularization, with subretinal fluid (arrowhead) present on Optovue B-scan (C). D-F, One week following the first treatment with bevacizumab, choroidal neovascularization was resolving on Cirrus OCT (D) and OCTA (E and F), with trace fluid (arrowhead in F). G and H, Four weeks following the first treatment with bevacizumab, OCTA showed decreased size and vascularity in choroidal neovascularization (arrowhead in G). I and J, Four weeks following the second treatment with bevacizumab, choroidal neovascularization (arrowhead in I) was barely visible on OCTA. C, F, H, and J, En face OCTA segmentation of the outer retina images is shown between the outer aspect of the inner nuclear layer (green line) and Bruch’s membrane (red line).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 1.
Conventional Imaging of Choroidal Neovascularization

A, Fundus photograph of the chorioretinal lesion lacking hemorrhage or fluid. B-D, Early-phase hyperfluorescence of the lesion at 20 seconds (B), staining at 1 minute (C), and hyperfluorescent peripheral spots at 5 minutes (D) on fluorescein angiography. E and F, Hypofluorescence of the lesion at 1 minute (E) and pinpoint late hyperfluorescence at 10 minutes (F) on indocyanine green angiography.

Graphic Jump Location

Tables

References

Jia  Y, Bailey  ST, Wilson  DJ,  et al.  Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014;121(7):1435-1444.
PubMed   |  Link to Article
Spaide  RF, Klancnik  JM  Jr, Cooney  MJ.  Retinal vascular layers in macular telangiectasia type 2 imaged by optical coherence tomographic angiography. JAMA Ophthalmol. 2015;133(1):66-73.
PubMed   |  Link to Article
Spaide  RF, Klancnik  JM  Jr, Cooney  MJ.  Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50.
PubMed   |  Link to Article
de Carlo  TE, Bonini Filho  MA, Chin  AT,  et al.  Spectral domain optical coherence tomography angiography (OCTA) of choroidal neovascularization [published online March 17, 2015]. Ophthalmology. doi:10.1016/j.ophtha.2015.01.029.
Kotsolis  AI, Killian  FA, Ladas  ID, Yannuzzi  LA.  Fluorescein angiography and optical coherence tomography concordance for choroidal neovascularisation in multifocal choroiditis. Br J Ophthalmol. 2010;94(11):1506-1508.
PubMed   |  Link to Article
Moult  E, Choi  W, Waheed  NK,  et al.  Ultrahigh-speed swept-source OCT angiography in exudative AMD. Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):496-505.
PubMed   |  Link to Article

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