Monitoring Ischemic Changes in Retinal Vasculitis With Optical Coherence Tomography Angiography

Abstract

Purpose:

This article illustrates the ability of optical coherence tomography angiography (OCTA) to aid in the diagnostic workup and management of occlusive retinal vasculitis over time.

Methods:

A case presentation is discussed.

Results:

In this case, OCTA helped define the extent and evolution of superficial and deep retinal capillary plexus occlusion and reperfusion over the treatment course.

Conclusions:

OCTA detects blood flow and maps retinal vasculature at the capillary level without the use of intravenous dye. Serial image acquisition can reveal patterns of ischemia and reperfusion in retinal vascular conditions as they evolve and respond to therapy, providing more granular information regarding the status of the retinal microvasculature that may guide treatment.

Introduction

Optical coherence tomography angiography (OCTA) is a noninvasive volumetric imaging modality developed in 2006 ¹ that remains in the early stages of clinical application discovery in the evaluation of ocular vasculature. The technique compares differences in back-scattered light intensity between sequential optical coherence tomography (OCT) images to deduce and map blood flow. ² Its natural application is the assessment of cross-sectional and longitudinal vascular changes in various ophthalmic diseases known or suspected to pathologically alter blood flow. Indeed, OCTA has helped elucidate degrees of vascular occlusion in a variety of inflammatory diseases such as Behçet disease, ³ Vogt-Koyanagi-Harada disease, ⁴ and acute macular neuroretinopathy. ⁵ OCTA may also be used to evaluate the impact of treatment on the restoration of blood flow. ⁶ We present the first reported case to our knowledge of mixed connective tissue disease (MCTD)–associated retinal vasculitis monitored by OCTA with findings characteristic of occlusive vasculitis that demonstrated improvement in pathologic blood flow over the course of systemic and local treatment.

Methods

Case Report

A 28-year-old woman with a history of hypothyroidism and amblyopia of the left eye presented with 4 days of progressively blurry vision, left eye greater than the right, amid intermittent headaches, fevers, and chills. Her vision was 20/25 OD and 20/150 OS, and findings from her pupillary examination were unremarkable. Her intraocular pressure was 10 mm Hg bilaterally. Confrontational visual fields showed bilateral nonspecific constriction. Results from an anterior segment examination were unremarkable. Dilated fundus examination revealed bilateral macular edema, hemorrhages, scattered cotton wool spots, and peripheral vascular sclerosis and sheathing without vitritis or optic nerve edema (Figure 1, A and B). OCT demonstrated hyperreflectivity suggestive of oncosis and edema in both eyes with subfoveal fluid in the left eye (Figure 1, I and J). Fluorescein angiography (FA) showed diffuse retinal small-vessel nonperfusion with late vascular leakage, which was consistent with bilateral active occlusive vasculitis (Figure 1, E and F).

Figure 1.

(A and B) Fundus photographs show macular edema, cotton wool spots, and hemorrhages surrounding the retinal arcades and in the macula, as well as vascular sheathing and sclerosis. (C and D) Fundus photographs show improvement in these changes at 5-month follow-up. (E and F) Fluorescein angiography (FA) shows occlusive retinal vasculitis with late vascular leakage in both eyes without disc leakage. (G and H) Follow-up FA at 5 months shows some improvement in areas of macular capillary nonperfusion and vascular leakage. (I and J) Initial optical coherence tomography (OCT) images show intraretinal edema and hyperreflectivity (diffusely and in areas also focally in the inner nuclear layer) in both eyes and subretinal fluid under the fovea in the left eye. (K and L) Follow-up OCT at 5 months shows improvement in the edematous changes with retinal thinning.

Results

An extensive rheumatologic workup ensued. Chest x-ray, contrast-enhanced magnetic resonance imaging of the brain and orbits, and magnetic resonance angiography of the head and neck were unremarkable. Laboratory tests revealed anemia (hemoglobin, 10.6 g/dL; reference range, 11.7-15.3 g/dL), elevated globulins (4.4 g/dL; reference range, 2.0-3.7 g/dL), and an elevated erythrocyte sedimentation rate (69 mm/h; reference range, 0-30 mm/h) and were positive for antinuclear antibodies (1:1280, discrete speckled) and weakly positive for lupus anticoagulants (dilute Russell viper venom time). Quantiferon gold (Qiagen) was indeterminate and test results for a purified protein derivative were negative. Remaining serologic workup findings, including for C-reactive protein, complement 3 and complement 4, rheumatoid factor, cyclic citrullinated peptide, angiotensin-converting enzyme, cardiolipin antibody, double-stranded DNA antibody, cytoplasmic-staining antineutrophil cytoplasmic antibodies, perinuclear- or nuclear-staining antineutrophil cytoplasmic antibodies, ribonucleoprotein, anti-Sjögren syndrome A and anti-Sjögren syndrome B, Smith antibody, Lyme disease, rapid plasma reagin, HIV, hepatitis B virus, and hepatitis C virus, were negative.

The rheumatology department initiated systemic immunosuppressant therapy, including mycophenolate and high-dose oral prednisone (60 mg/d) for suspected MCTD. One week later, the patient’s vision was 20/40 OD and 20/600 OS. OCTA showed extensive bilateral superficial and deep retinal capillary dropout (Figures 2 and 3, A and D). After discontinuing systemic therapy against medical advice, she was treated locally with sub-Tenon triamcinolone injections (30 mg), 2 (right eye) and 3 (left eye) weeks after presentation. Her vision improved to 20/20 OD and 20/30 OS at 5-month follow-up. OCTA was used on follow-up to monitor retinal perfusion and determine therapy response (Figure 1, C, D, G, H, K, and L; Figures 2 and 3, B, C, E, and F), guiding management of retinal vasculitis.

Figure 2.

(A, B, and C) Optical coherence tomography angiography (OCTA) images of the superficial retinal capillary plexus in the right eye at 1 week, 10 weeks, and 5 months posttreatment initiation show gradual improvement in areas of macular capillary nonperfusion. (D, E, and F) Corresponding OCTA maps of the deep retinal capillary plexus show no obvious areas of reperfusion throughout the follow-up period.

Figure 3.

(A, B, and C) Optical coherence tomography angiography (OCTA) images of the superficial retinal capillary plexus in the left eye at 1 week, 10 weeks, and 5 months posttreatment initiation show gradual improvement in areas of macular capillary nonperfusion and intraretinal edema. (D, E, and F) Corresponding OCTA maps of the deep retinal capillary plexus likewise show temporal improvement in retinal edema and capillary dropout.

Conclusions

Thirty percent of patients with MCTD show findings consistent with retinal vasculitis on FA, including staining of thickened vessel walls and progressive vascular leakage, which is a higher incidence than that observed in patients with Sjögren disease or systemic lupus erythematosus. ⁷ The mechanism of these vascular changes is unknown, and although some patients respond well to low-dose oral prednisolone alone, ⁸ others have shown poor visual outcomes despite multiple high-dose immunosuppressants, especially when complicated by larger vascular occlusions. ⁹

FA is the classic criterion-standard diagnostic tool for assessing occlusive and nonocclusive, inflammatory vascular changes. Over the past decade, OCTA has been increasingly used as a supplementary tool and for some cases proposed as a noninvasive alternative to FA for evaluating and monitoring retinal and choroidal vasculopathies in a variety of conditions from diabetes to sympathetic ophthalmia. ^10,11 Although FA allows for the dynamic assessment of clues to inflammation such as vascular leakage, it is time consuming, invasive, and does not allow one to individually evaluate changes in retinal vascular beds in different planes. OCTA, in contrast, allows one to differentially assess occlusive changes in multiple planes of vascular beds. For example, Khairallah et al demonstrated capillary dropout in both the superficial and deep retinal capillary plexus in a patient with West Nile virus–associated chorioretinitis that persisted a month later despite improvement in vision and ischemic retinal whitening lesions on topical immunosuppressive therapy. ¹² OCTA allowed Somkijrungroj and colleagues to propose relative deep capillary plexus nonperfusion as a mechanism underlying vision loss in Behçet disease even among patients with normal-appearing foveal avascular zones on FA. ³ Aggarwal et al and Liu and colleagues used OCTA to monitor improvement in retinal capillary disruption in patients with acute macular neuroretinopathy with and without treatment with oral steroids, respectively. ^5,6

OCTA of our patient showed improvement in her superficial and deep capillary plexus deficits with a granularity finder than could be provided by FA months after treatment while her vision and other retinal lesions also improved. OCT was inadequate to monitor her posttreatment improvement of edema and accurately observe the degree of active ischemia and vasculitis. OCTA, in contrast, was better equipped to monitor these changes and the patient’s response to treatment. It is also more feasible and less invasive than obtaining FAs at each follow-up visit, producing measurable differences in ischemia and blood flow that can guide treatment decisions. It is worth mentioning, however, that there are a number of limitations to OCTA, including the need for adequate fixation during image acquisition, image artifacts (eg, projection artifact or signal corresponding to more superficial vessels than it appears), the static nature of the images acquired, and the inability to demonstrate vascular leakage.

To date this is the first reported case to our knowledge of MCTD-associated vasculitis monitored by OCTA, and it may serve as a novel means for monitoring the disease in the future. This diagnostic tool represents a noninvasive, time-efficient supplement to traditional dye-based retinal vascular imaging techniques that can serve as a useful alternative when monitoring retinal vascular changes over time. Further research is necessary to better define the role of OCTA in qualitatively and quantitatively assessing and monitoring chorioretinal vascular disease as well as identifying useful prognostic markers to guide its management.