Multimodal imaging in Behçet disease uveitis manifesting with sequential bilateral prepapillary inammatory vitreous exudate

Objective: To describe a case of Behçet disease (BD) uveitis manifesting with sequential bilateral prepapillary inammatory vitreous exudate (PIVE) documented with multimodal imaging, including swept source optical coherence tomography (SS OCT) and OCT angiography. Material and Methods: A single case report. Results: A 37-year-old man developed sequential bilateral PIVE, initially misdiagnosed as toxoplasmic neuroretinitis, before extraocular features of BD became evident and the patient treated accordingly. SS OCT showed at the acute phase in both eyes a typical “mushroom-shaped” prepapillary hyperreectivity of the PIVE. SS OCTA demonstrated a corresponding prepapillary hypointense area due to shadowing effect, decreasing in size while scanning deeper layers. It also detected peripapillary retinal hypervascularity in both eyes and a sectoral area of ow signal loss in the rst involved left eye. Visual acuity improved following the resolution of the PIVE and associated acute inammatory changes in both eyes. The left eye showed residual optic disc pallor and retinal nerve ber layer defects. Conclusion: Sequential bilateral PIVE may occur in the absence of other clinical features of BD. SS OCT and OCTA can provide useful information for the diagnosis and management of PIVE and underlying optic nerve inammation.


Introduction
Behçet disease (BD) is a multisystemic in ammatory disorder of unknown etiology characterized by recurrent in ammatory attacks. 1 . Most common manifestations of BD include oral ulcers, genital ulcers, and ocular involvement. Ocular BD is typically characterized by bilateral relapsing-remitting non granulomatous panuveitis with retinal vasculitis that may result in severe vision loss 1 . Several speci c eye ndings may help in the early diagnosis of BD uveitis and in differentiating this condition from other infectious and non-infectious uveitis entities 2,3 . These include shifting hypopyon, diffuse vitritis, inferior vitreous precipitates, transient super cial retinal in ltrates, occlusive retinal vasculitis, and fern-like retinal capillary leakage.
Optic disc hyperemia is a constant feature of posterior segment in ammation and optic disc hyper uorescence is an early uorescein angiographic nding in patients with BD uveitis 3 . Other rare forms of optic nerve involvement have been described including optic neuritis, neuroretinitis, unilateral prepapillary vitreous exudate, and ischemic optic neuropathy 2 .
We herein describe a case of BD uveitis manifesting with sequential bilateral prepapillary in ammatory vitreous exudate (PIVE) documented with multimodal imaging, including swept source optical coherence tomography (SS OCT) and OCT angiography.

Case Report
A 37-year-old man presented with sudden blurred vision in the left eye (LE). Best-corrected visual acuity (BCVA) was 20/20 in the right eye (RE) and 20/200 in the LE, and there was a left relative afferent pupillary defect (RAPD). Intraocular pressure was 16 mm Hg bilaterally. Slit-lamp examination of the RE showed no evidence of intraocular in ammation in the anterior chamber or vitreous cavity. Results of fundus examination of the RE were unremarkable. Slit-lamp examination of the LE showed a quiet anterior chamber and 1 + vitreous cells. Fundus examination of the LE revealed a localized in ammatory vitreous exudate overlying an in ltrated optic disc and peripapillary retina with associated retinal hemorrhages (Fig. 1A). There was no evidence of retinal vascular sheathing, retinal in ltrates, or any other abnormality elsewhere in the left fundus. Late-phase fundus uorescein angiography (FFA) of the LE showed optic disc leakage and a masking effect from retinal hemorrhages (Fig. 1B). Swept-source OCT (SS-OCT) (DRI OCT Triton plus, Topcon, Tokyo, Japan) of the optic nerve head showed a "mushroom-shaped" hyperre ectivity of the PIVE seen clinically (Fig. 1C). There was an associated shallow macular serous retinal detachment (Fig. 1D). SS OCTA of the LE revealed a dark area overlying the optic disc and peripapillary retina due to blockage from the PIVE. This hypointense area was found to decrease in size while scanning deeper layers, re ecting the "mushroom-shaped" hyperre ectivity of the PIVE (Fig. 1E,F,G). There was a surrounding retinal hypervascularity with a sectoral superotemporal hyposignal area. Macular OCTA showed no obvious abnormal ndings. Results of FFA, OCT, and OCTA of the RE were unremarkable.
The patient denied any prior history of speci c systemic symptoms. A diagnosis of presumed toxoplasmic neuroretinitis was made based on a positive anti-toxoplasmic IgG titer and a negative laboratory work-up for other infectious and non-infectious causes of uveitis and neuroretinitis. These included cat scratch disease, rickettsial disease, tuberculosis, syphilis, sarcoidosis, and BD. The patient was treated with the association of azithromycin (500 mg the rst day, and then 250 mg/day), pyrimethamine (100 mg the rst day, and then 50 mg/day), folinic acid (15 mg/day), and oral prednisone (0.75 mg/kg/day). After 4 weeks of therapy, visual acuity of the LE had improved to 20/32, and the PIVE and associated optic disc and peripapillary in ltration had completely resolved (Fig. 1H).
One year after the initial presentation, the patient complained of acute vision loss in the RE. BCVA was 20/200 in the RE and 20/20 in the LE, and there was a right RAPD. Slit-lamp examination showed a quiet anterior chamber and 2 + vitreous cells in the RE. There was no evidence of intraocular in ammation in the anterior chamber or vitreous cavity in the LE. Fundus examination of the RE revealed a localized PIVE overlying an in ltrated optic disc and peripapillary retina with associated retinal hemorrhages ( Fig. 2A). There was no evidence of retinal vascular sheathing, retinal in ltrates, or any other abnormality elsewhere in the right fundus. Fundus examination of the LE showed a mild temporal optic disc pallor with superotemporal bundle retinal nerve ber layer (RNFL) defects (Fig. 3A). SS OCT of the RE showed a "mushroom-shaped" hyperre ectivity of the PIVE seen clinically and the presence of peripapillary subretinal uid involving the fovea (Fig. 2B). An OCTA scan in the RE through the radial peripapillary capillary network showed a hypointense area overlying the optic disc and peripapillary retina due to blockage from the PIVE. There was a surrounding peripapillary retinal hypervascularity with a peripapillary vascular density (PVD) of 11.23% (Fig. 2C). OCT retinal thickness analysis of the LE showed RNFL thinning at the superotemporal region corresponding to the RNFL defects seen clinically, with an area of subclinical inferotemporal RNLF thinning ( Fig. 3B and C). Results of OCT and OCTA of the LE were unremarkable.
Physical examination by an internist revealed a recent history of recurrent oral ulcers and showed the presence of genital aphthous ulcers, pseudofolliculitis, and papulopustular lesions. A nal diagnosis of BD was made based on a score of 5 according to the International Criteria for diagnosis of Behçet's Disease 4 . The patient was treated with oral prednisone (1 mg/kg/day, followed by gradual tapering) and azathioprine (3 mg/kg/day).
Sequential follow-up examinations showed gradual resolution of acute in ammatory changes and improvement of visual acuity in the RE. At the one-month follow-up, BCVA was 20/20 in the RE and remained unchanged at 20/32 in the LE. There were no cells in the anterior chamber or vitreous cavity in either eye. Fundus examination of the RE showed complete resolution of the PIVE and underlying optic disc and peripapillary in ltration and the development of macular hard exudates ( Fig. 2D and G). SS OCTA showed the resolution of the prepapillary hyposignal area and decrease in peripapillary hypervascularity, with a PVD of 9.18% ( Fig. 2F and I). Over a further 6-month follow-up period, BCVA remained stable, the macular hard exudates in the RE gradually resolved, and no in ammatory are-ups occurred.

Discussion
Prepapillary in ammatory vitreous exudate (PIVE), also termed prepapillary in ammatory vitreous opacity, condensation, or in ltrate, is an uncommon nding in active BD uveitis [5][6][7] . There are only a few reports that speci cally addressed this nding in literature 5,7 . In all reported cases, patients had a prior history of BD and presented with bilateral panuveitis with retinal vasculitis in association with unilateral PIVE.
In this report, we describe for the rst time a case of sequential bilateral isolated PIVE secondary to BD documented with SS OCT and OCTA. The initial unilateral PIVE occurred in association with marked optic disc and peripapillary in ltration and in the absence of signi cant in ammatory changes elsewhere in the fundus. An initial diagnosis of presumed toxoplasmic neuroretinitis was made in the presence of a positive toxoplasmosis serology and a negative systemic work-up for other relevant causes of posterior uveitis and neuroretinits including BD. The PIVE and underlying optic disc and peripapillary in ltration rapidly resolved, with improvement of visual acuity. One year later, a similar transient PIVE developed in the fellow eye. Typical mucocutaneous lesions became evident, and the patient therefore was diagnosed with de nite BD and accordingly treated with corticosteroid and immunosuppressive therapy.
SS OCT was useful in con rming the diagnosis of PIVE in both sequentially involved eyes by showing a characteristic prepapillary hyperre ective "mushroom-shaped" lesion. It also allowed us to detect an associated serous retinal detachment and to exclude any obvious peripapillary or subfoveal choroidal changes. SS OCTA showed at the acute phase a hypointense prepapillary area due to shadowing from the PIVE. This hypointense area was found to characteristically decrease in size while scanning deeper, re ecting the "mushroom-shaped" hyperre ectivity seen on SS OCT. SS OCTA also allowed us to detect subclinical peripapillary vascular involvement with retinal hypervascularity and increased vessel density which gradually resolved over time. In addition to that, the initially involved left eye demonstrated a peripapillary superotemporal area of signal loss which could explain the subsequent development of RNFL defects in the same eye. Localized RNFL defects have been considered in BD uveitis as an indicator of past retinal or optic nerve involvement and as a helpful ocular diagnostic clue 8 . Our results, consistent with previous data 3,8 , show that RNFL defects can be easily detectable by fundus examination, but OCT and RNFL thickness analyzer are useful in con rming the diagnosis and detecting subclinical RNFL alterations.
The bilateral sequential PIVE in our patient likely occurred due to the spread of in ammation from primary severe optic nerve in ltration 7 .
The « mushroom-shaped » or « funnel-shaped » OCT pattern of BD-associated PIVE might be due to polymorphic leukocytic in ltration into the enlarged end of Cloquet's canal 5,7 .
This report shows that bilateral sequential PIVE, indicative of severe optic nerve in ammation, can occur prior to other ocular and systemic manifestations of BD, and this may lead to mistakes in diagnosis and management. Multimodal imaging including FFA, OCT, and OCTA can provide valuable information for the de nitive diagnosis and appropriate management of BD-associated PIVE and underlying neuroretinitis. The datasets used and/or analysed during the current study are available from the corresponding author on request.

Competing interests:
The authors declare that they have no competing interests  hypointense area decreases in size while scanning deeper layers, re ecting the "mushroom-saphed" pattern of the prepapillary vitreous exudate. Note the presence of a superotemporal hyposignal area (arrows). One month after presentation, SS OCT shows the resolution of the prepapillary vitreous exudate and serous retinal detachment (H, I).

Figure 2
Multimodal imaging at the time of presentation for the right eye involvement. (A) Fundus photograph of the right eye showing a localized in ammatory vitreous exudate overlying an in ltrated optic disc and peripapillary retina with associated retinal hemorrhages. (B) SS OCT showing a "mushroom-shaped'' hyperre ectivity of the prepapillary vitreous exudation associated with a peripapillary serous retinal detachment involving the fovea. (C) SS OCTA scan through the radial peripapillary capillary network of the right eye revealing a prepapillary hypointense area due to blockage from the prepapillary exudate. Note the presence of peripapillary retinal hypervascularity, with a peripapillary vascular density (PVD) of 11.23%. Sequential imaging follow-up at 48 hours (D,E,F) and one month (G,H,I). Fundus photography shows the development of macular hard exudates and gradual resolution of the prepapillary in ammatory exudate and associated optic disc and peripapillary in ltration (D and G). SS OCT demonstrating gradual resolution of the prepapillary hyperre ectivity and subretinal uid (E and H). SS OCTA showing gradual resolution of the prepapillary hypointense area and peripapillary hypervascularity, with a PVD of 9.18% at one month (H, I).