Microvasculopathy in Lyme-associated papillitis revealed by optical coherence tomographic angiography

CASE REPORT

Lyme disease is a tick-borne illness caused by the Borrelia burgdorferi spirochete and transmitted by the Ixodes tick (1). Lyme disease can manifest in the posterior pole, commonly in the form of papillitis (1). Diagnosis of Lyme papillitis requires a thorough workup to eliminate other infectious and autoimmune etiologies of papillitis in addition to positive serologic and/or cerebrospinal fluid (CSF) markers (2). Previous reports of optic nerve involvement in Lyme disease have been attributed to increased intracranial pressure or inflammatory papillitis.(3) More rare neurologic manifestations of Lyme disease include cerebral and retinal vasculitis in addition to stroke (1, 4). We report a case of Lyme papillitis with peripapillary capillary attenuation evident on OCT-A that may suggest ischemic injury imparted by Lyme infection at the optic nerve head as a contributor to visual loss.

A 63-year-old man living in rural New England with a history of idiopathic thrombocytopenic purpura on monthly rituximab infusions and oral prednisone (10 mg daily), systemic hypertension, hyperlipidemia, and alcoholic cirrhosis presented with two weeks of cloudy vision in his left eye. He reported myalgias, jaw claudication and scalp tenderness. Visual acuities were 20/20 in the right eye and 20/30–1 in the left eye. A relative afferent pupillary defect was present in the left eye. Humphrey visual fields revealed an inferior arcuate defect in the left eye (Figure 1A,B-insets). Right greater than left optic disc edema and peripapillary flame hemorrhages were appreciated funduscopically (Figure 1A,B). Fluorescein angiography revealed filling defects in the left optic nerve head most prominent superiorly and aneurysmal dilatation inferiorly; later images for the right eye showed diffuse aneurysmal dilation and papillary leakage (Figure 1C,D). OCT-A showed expansion of the papillary capillary network for the more edematous right optic disc and decreased OCT-A signal in the left peripapillary region most prominent superiorly (Figure 1E,F). OCT of the macula showed normal anatomy in the right eye and superotemporal perifoveal thinning of the ganglion cell complex with subtle focal superficial microvascular attenuation on OCT-A in that area of the left eye (Figure 1G,H).

Figure 1. Ocular imaging including Optic Coherence Tomographic Angiography (OCT-A) on presentation of bilateral Lyme-associated optic neuropathy.

(A-B) Fundus photography of the right (A) and left (B) eyes demonstrating right>left optic disc edema with peripapillary flame hemorrhages. Insets show automated perimetry (Humphrey 24–2 SITA) results for each eye, respectively. (C-D) Fluorescein angiography showing diffuse papillary leakage with aneurysmal dilation in right eye (C) and a superior perfusion defect (yellow arrow) and inferior aneurysmal dilatation in the left optic disc (D). Insets show the time post-infusion (minutes:seconds). (F-H) OCT-A images with corresponding B-scan images through the center of the optic dis or fovea depicting segmentation (Avanti, Optovue, Fremont, CA, USA). (E-F) Papillary and peripapillary OCT-A images with retinal segmentation (upper and lower boundaries depicted by red lines) showing diffuse expansion of the papillary and peripapillary capillary network for the right eye (E) and attenuation of the papillary and peripapillary network most prominent superiorly (yellow arrow) in the left eye (F). (G-H) Macular OCT-A images with superficial segmentation (upper boundary depicted by red and lower boundary depicted by green lines) showing normal microvasculature in the right eye (G) and focal capillary attenuation in the superotemporal macula (yellow arrows) in the left eye (H). Insets show ganglion cell complex heat maps (composite retinal nerve fiber layer, ganglion cell layer and inner plexiform layer relative to normative controls) showing normal results in the right eye and thinning superotemporal to the fovea in the left eye, respectively.

Gadolinium-enhanced MRI of the brain and orbits demonstrated elevated T2 signal without enhancement in the left optic nerve and a normal right optic nerve. Laboratory workup revealed an elevated white blood cell count (12.36 K/uL, 92% neutrophils), normocytic anemia (hgb 10.6 g/dL), elevated platelets (402 K/uL), elevated sedimentation rate and C-reactive protein (97mm/h and 65.2 mg/L), and negative Syphilis serology.

The patient was treated for presumed giant cell arteritis with IV methylprednisolone 1g daily for 3 days, followed by an oral prednisone taper from 80 mg to 60 mg daily. A temporal artery biopsy (2.8 cm 2 days after presentation) was negative. The acuity in his left eye declined to the hand motions level with persistently elevated inflammatory markers. He was readmitted and given IV methylprednisolone again for 3 days, followed by oral prednisolone at 100 mg tapering to 80 mg daily. A second temporal artery biopsy 11 days after initial presentation (1 cm) was negative. Despite continued treatment with high dose corticosteroid and addition of tocilizumab, the patient continued to gradually lose vision in both eyes. Further work-up revealed positive anti-Lyme IgG (8, 23, 39, 58 and 66 kDa bands), IgM (23 and 41 kDa bands) antibodies in the blood, and separate samples obtained at the time of lumbar puncture revealed antibodies in CSF (IgG: 2.6 relative to background; IgA: >5.0 relative to background) and blood including IgA (2.3 relative to background). A CSF/serum IgA ratio of 2.2 was consistent with intrathecal synthesis (5). Following a 28-day course of IV ceftriaxone, his visual acuity improved to 2/200 OS and remained stable OD at 20/30 for follow-up over 2 years.

Lyme papillitis often poses a diagnostic challenge. Diagnostic criteria for Lyme-associated optic neuropathy include definitive proof of active Lyme infection by way of culture or histologic evidence of B. burgdorferi in the CSF or optic nerve (2). Strong evidence implicating Lyme as causative in this case include exclusion of other causes of inflammatory/infectious optic neuropathy, exposure to an endemic area, myalgias, positive serum titers, CSF pleocytosis, and intrathecal Lyme antibodies with a CSF/serum ratio supportive of intrathecal synthesis (2). As such, the patient reported herein met the criteria for strong evidence supporting the diagnosis of Lyme papillitis. Further support is lent by his worsening with corticosteroid and tocilizumab treatment, and his improvement and stability following antibiotic treatment.

OCT-A allows for detailed imaging of the retinal and papillary microvasculature and has been used in the evaluation of various causes of optic disc edema including anterior ischemic optic neuropathy, papilledema and optic neuritis (6–8). Previous reports have identified dilation of the peripapillary capillary network in the acute phase of non-arteritic anterior ischemic optic neuropathy (NAION) and arteritic anterior ischemic optic neuropathy (AAION) (7, 8). In addition, focal attenuations in the superficial peripapillary capillary network have been reported in the setting of giant cell arteritis (7).

In the case presented herein, there was significantly more capillary attenuation in the left optic disc compared to the right that corresponded with visual function at the time of presentation and final outcome. Importantly, the focal area of capillary attenuation in the left superior optic disc seen on FA and OCT-A corresponded to the superior perifoveal thinning of the ganglion cell complex and subtle superficial microvascular attenuation on macular OCT/OCT-A (Figure 1D,F,H). These defects correspond to and likely account for the inferior altitudinal defect on visual field testing. The attenuation of OCT-A signal at the left optic nerve head is unlikely to represent an imaging artifact because one would expect segmentation error or obscuration by edema to be greater in the more edematous right optic nerve, which actually showed expansion of the peripapillary capillary network. Thus, the OCT-A findings in this case reliably demonstrate microvascular defects in the optic nerve head associated with visual loss secondary to Lyme papillitis, and these changes better reflected the functional status of the optic nerve than the fundus appearance.

The pathophysiology of Lyme papillitis remains elusive; it remains unclear whether tissue damage occurs secondary to an immune mediated process or infiltration and destruction by B. Burgdoferi (3). In this case, the peripapillary capillary attenuation in the optic disc that was less edematous may represent vascular compromise related to that observed in Lyme-associated cerebral vasculitis (4) or retinitis (1). Lyme-associated cerebral vasculitis occurs secondary to perivascular and vascular lymphocytic infiltration induced by B. burgdoferi, resulting in thickening of small, medium and large arteries, and consequential narrowing and occlusion (4). It stands to reason that a similar process may occur at the optic nerve head, for which B. burgdoferi has a clear predilection.

This unique case highlights the utility of OCT-A to identify microvasculature changes in the papillary network in an infectious cause of papillitis. The OCT-A findings described herein should not be considered specific for this condition, but may signify a potential vaso-occlusive/ischemic component of optic nerve injury, by contrast to other proposed mechanisms (3). Further study is needed, perhaps employing more advanced ocular imaging technology, to confirm these findings in Lyme papillitis. In addition, the peripapillary capillary attenuation visualized during the acute phase corresponded with visual function on presentation and after treatment, suggesting that OCT-A may serve as a better prognostic indicator than the clinical exam in Lyme papillitis.