Sympathetic ophthalmia (SO) is a rare cause of granulomatous panuveitis. The diagnosis of SO is based on history and clinical examination. Fluorescein angiography (FA),1 indocyanine green angiography (ICGA),2 and optical coherence tomography (OCT) are useful adjuncts in establishing the extent and severity of SO.3
The mainstay of treatment is long term systemic immunomodulatory therapy.4 The clinical criterion for response to therapy incorporates an appraisal of the inflammatory response, such as the degree of choroiditis and papillitis on exam and with imaging using OCT, FA, and ICGA.5,6 Additionally, OCT angiography (OCTA) now provides a detailed, depth-resolved reconstruction of the retinochoroidal microvasculature and is useful in posterior uveitis.7,8
We report a case of SO and highlight the use of widefield montage swept-source OCTA (SS-OCTA) to monitor detection of and changes in choriocapillaris flow voids as an indicator for treatment response on systemic immunosuppression.
A 36-year-old male presented with 2 weeks of blurred vision and floaters in his left eye. He had no light perception in his right eye following penetrating ocular trauma in his childhood. His best-corrected visual acuity (VA) in the left eye was 20/60. Anterior segment evaluation of the right eye revealed ciliary congestion with an adherent leucoma (Figure 1a). The details of the posterior segment could not be visualized in the right eye, and ultrasound showed disorganized globe contents. Left eye anterior segment examination showed ciliary injection, 2+ cells and flare in the anterior chamber, mutton fat keratic precipitates on the corneal endothelium, retrolental flare, and anterior vitreous cells. Intraocular pressure (IOP) was non-recordable in the right eye and 25 mm Hg in the left eye. On fundus examination, there was 2+ vitreous haze, optic disc edema and hyperemia, and tortuous retinal vessels, and a few deep retinal lesions were faintly visible in the superior midperiphery (Figure 1b). FA demonstrated multiple early hypofluorescent spots (Figure 1c) with late hyperfluorescence and marked perivascular and disc leakage (Figure 1d). En face and cross-sectional SS-OCTA images (PLEX Elite 9000 version 1.5; Carl Zeiss Meditec, Dublin, CA) were analyzed to study the different retinochoroidal slabs using a montage of 12 mm × 12 mm scans. The superficial and deep retinal capillary plexus did not show any pathological changes at presentation (Figures 2a and 2b). OCTA at the level of choriocapillaris, however, showed multiple hyporeflective areas of variable size and shape, which likely represented areas of choriocapillaris hypoperfusion (Figure 2d). Corresponding structural en face OCTA did not reveal any additional signal loss (other than shadow artifact due to overlying vitreous opacity), which suggested that the hyporeflective areas were likely consistent with reduced flow (Figure 2d). OCT scan through the fovea showed subretinal hyperreflective material in the peripapillary area with multiple sub-retinal pigment epithelium (RPE) drusenoid like accumulations in the macula. (Figure 2f). Montage 12 mm × 12 mm OCTA scans at the level of the choriocapillaris (Figure 3a) showed the flow voids extending throughout the posterior pole. Structural OCT with flow overlay (Figure 3d) showed a significant reduction in flow and enhanced depth imaging (Figure 3g) showed significant choroidal thickening.
External photograph (a) shows the exciting blind right eye with no light perception following traumatic injury 20 years ago. Fundus photography (b) of the sympathizing left eye with acute sympathetic ophthalmia shows presence of vitritis with disc swelling and perivasculitis in the posterior pole. Fluorescein angiography in the early frame (c) shows early pin-point hypofluoresent spots in the superior midperipheral area and early disc hyperfluorescence. In the late frame of the angiography (d), there is leakage at the disc and diffuse perivascular leakage. Follow-up photograph at 6 months shows resolution of disc swelling and vitreous haze, along with significant reduction in vitreous opacities (e).
Swept-source optical coherence tomography (OCTA) 12 mm × 12 mm scan at the level of the superficial (a) and deep capillary plexus (b) does not show any structural retinal abnormality. At the level of the outer retina to choriocapillaris slab, (c) multiple dark spots are seen, and OCTA slab at the level of choriocapillaris (c) also shows presence of multiple dark areas scattered all across the posterior pole. Corresponding en face OCTA does not reveal any segmentation or structural abnormality (e). There is, however, an overlying shadow artifact due to vitreous opacities, which projects on all the slabs (a–e). Enhanced depth imaging OCT (f) shows multiple retinal pigment epithelium drusenoid-like elevations, peripapillary subretinal hyperreflective material, and a thickened choroid.
Serial swept-source optical coherence tomography (OCTA) montage scans of multiple 12 mm × 12 mm scans at the level of the choriocapillaries at presentation and follow-up (top row). There are multiple dark foci of flow voids of different shapes and sizes throughout the posterior pole consistent with likely choriocapillaris hypoperfusion at presentation. (a) At 3 months' follow-up, with initiation of systemic immunosuppression, there is a significant reduction in the size and number of these spots (b). At 6 months' follow-up, there is near complete resolution, with only a few flow voids still visible (yellow ovals, c). The optic nerve is darker in (c) due to a shadow artifact from overlying vitreous opacity. Structural OCT scans with flow overlay (middle row) show significant reduction of flow (red dots) at the level of the choriocapillaris and the choroid at presentation (d), with progressive restoration of flow at 3 months (e) and further at 6 months (f). Enhanced depth 16-mm horizontal OCT scans (bottom row) showing a very thickened choroid along with peripapillary subretinal hyperreflective material and multiple retinal pigment epithelium (RPE) drusenoid-like elevations in the macula at presentation (g). At 3 months, there is reduction in the peripapillary subretinal hyperreflective material and choroidal thickness along with partial restoration of the external limiting membrane and ellipsoid zone and reduction in the RPE drusenoid like elevations (h). By 6 months, there is near complete resolution of the RPE drusenoid-like elevations (i).
Based on the typical history and clinical signs, and after negative testing for tuberculosis, syphilis, and sarcoidosis, a diagnosis of sympathetic ophthalmia was made, and the patient was initiated on high-dose intravenous steroids with 1 gram pulse for 3 consecutive days along with topical steroids, cycloplegics, and IOP-lowering medications. The patient was then switched to oral prednisolone (1 mg/kg/day) for 1 week and then slowly tapered during the next 3 months. At 3 weeks of follow-up, the patient was symptomatically better, with improvement in VA to 20/20. Oral steroids were further tapered and steroid sparing immunosuppression (antimetabolite azathioprine) was initiated after baseline blood tests (complete blood count with differential and comprehensive metabolic panel) at a dose of 50 g/day for 1 week and then increased to 100 mg /day. At 3 months, vision was maintained at 20/20 and there was no sign of relapse. Azathioprine (Azasan; Salix Pharmaceuticals, Raleigh, NC) and a low dose of oral steroid (10 mg/day) were well-tolerated, with normal blood counts and liver function tests.
Follow-up montage OCTA 12 mm × 12 mm scans showed a reduction in the number and size of areas of the hyporeflective areas at the level of the choriocapillaris at 3 months (Figure 3b), and at 6 months there was almost complete resolution of these hyporeflective spots with continued systemic immunosuppression (Figure 3c). Structural OCT with flow overlay showed improved flow at 3 months (Figure 3e, red dots) with further improvement at 6 months (Figure 3f). Follow-up enhanced depth imaging showed reduction of choroidal thickness, subretinal hyperreflective material, and drusenoid-like RPE elevations along with restoration of the external limiting membrane and ellipsoid zone at 3 months (Figure 3h) and 6 months (Figure 3i).
Onset of SO usually occurs within the first year after injury in 90% of patients, but late presentations have been reported at up to 66 years.9–11 Our case had a delayed presentation, almost 20 years after initial trauma.
Pathophysiological studies on SO have identified Dalen-Fuchs nodules, which are found in approximately one-third of enucleated eyes thought to have SO.12 Histologic sections and immunostaining demonstrate that Dalen-Fuchs nodules, seen as nummular, depigmented, chorioretinal spots on exam, can be found within the choroid, under the RPE, or under the neurosensory retina, and these are thought to represent choroidal inflammatory cellular infiltration.11 Jennings et al. suggested that the clinical appearance of Dalen-Fuchs nodules appeared to correlate with the severity of the disease.13 In the active phase of SO, ICGA — which was not available in our case — usually shows multiple hypocyanescent spots believed to represent focal, choroidal, inflammatory infiltrates.2 On OCT, Dalen-Fuchs nodules appear as small, irregular, hyperreflective pigment epithelial detachments, often with disruption of the overlying RPE and extension of the hyperreflective, presumed inflammatory, material into the outer retina that over time evolve to focal chorioretinal scars, with circumscribed loss or disruption of the outer retina and inner choroid.14
OCTA is capable of identifying such lesions, and it aids in diagnosis by identifying features of choriocapillaris ischemia in eyes with SO. More importantly, OCTA can be used to follow the progression of these flow voids as a marker to monitor treatment response (Figure 3). It allows easily repeated, registered, follow-up imaging and reduces the need for frequent ICGA.8 When evaluating uveitic diseases, a large field of view with good detail of the retinal vasculature is important. Traditionally, FA is capable of widefield imaging of the retinal vasculature. However, it is invasive, and visualization of the retinal vasculature is limited in cases with retinal hemorrhage, scarring, or early leakage. OCTA aids in diagnosis by identifying features of choriocapillaris ischemia has traditionally been limited to a smaller field of view. However newer prototype machines now offer widefield montage images that allow for improved visualization of the retinal vasculature. A montage of multiple 12 mm × 12 mm OCTA images provide a much larger field of view, making it almost comparable to conventional FA. Our report demonstrates detection of choriocapillaris pathology till the retinal midperiphery using montage OCTA (Figure 3c).
OCTA does have limitations, including the presence of several artifacts such as signal loss and errors in segmentation, especially in eyes with intraocular inflammation. Evaluation of the far peripheral retinal vasculature is still difficult to image even after using widefield OCTA, and there may be errors during montage creation. Additionally, we were unable to correlate OCTA findings with ICGA, as access to ICGA was not available.
In conclusion, this case highlights the potential utility of widefield montage SS-OCTA for detecting and monitoring choriocapillaris flow voids in SO, which can be used as a marker for treatment response. Larger studies are needed to fully characterize these changes on OCTA with disease progression and their improvement with treatment.
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- Gallagher MJ, Yilmaz T, Cervantes-Castañeda RA, Foster CS. The characteristic features of optical coherence tomography in posterior uveitis. Br J Ophthalmol. 2007;91(12):1680–1685. doi:10.1136/bjo.2007.124099 [CrossRef]
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