Journal of Neuro-Ophthalmology:
Optic Perineuritis as the Presenting Feature of Crohn Disease
McClelland, Collin MD; Zaveri, Maulik MD; Walsh, Ryan MD; Fleisher, Jori MD; Galetta, Steven MD
Division of Neuro-Ophthalmology, Departments of Neurology and Ophthalmology (CM, RW, SG); and Departments of Ophthalmology (MZ) and Neurology (JF) Perelman/University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Address correspondence to Collin McClelland, MD, Washington University in St. Louis School of Medicine, Department of Ophthalmology & Visual Sciences, 660 South Euclid, Campus Box 8096, St. Louis, Missouri, 63110; E-mail: firstname.lastname@example.org
The authors report no conflicts of interest.
Abstract: Crohn disease (CD) is primarily considered an inflammatory condition of the small and large intestine although associated extraintestinal inflammation is relatively common. Ocular manifestations are generally localized to the anterior chamber and ocular surface but rarely can involve the posterior pole, orbit, and optic nerve. We report a case of an otherwise healthy 42-year-old man who was diagnosed with CD after presenting with acute vision loss from optic perineuritis.
Crohn disease (CD) is a chronic inflammatory condition characterized by scattered areas of focal transmural granulomatous inflammation of the small and large intestine (1). CD and ulcerative colitis (UC) constitute the 2 leading causes of inflammatory bowel disease (IBD). Although gastrointestinal (GI) symptoms predominate in IBD, extraintestinal inflammatory manifestations are common, with an estimated prevalence of 20–40% (2). The eye is often a site of extraintestinal involvement in CD. We report a patient with optic perineuritis (OPN) as a presenting feature of CD and review the literature on associations between ocular disease and CD.
A previously healthy 42-year-old Caucasian man presented to the emergency room following acute, painless loss of the entire visual field in the left eye that morning. A review of systems revealed 10 days of abdominal cramping, low-grade fever, and diarrhea. Visual acuity was 20/20, right eye, and hand motions, left eye. Visual fields were full to confrontation technique in the right eye and showed a large central scotoma in the left eye. Pupils demonstrated a left relative afferent pupillary defect. Ocular motility and alignment were normal. Applanation tonometry revealed intraocular pressures of 6 mm Hg in both eyes. Slit-lamp examination was significant for mild conjunctival injection with 1+ anterior chamber cells in both eyes, and funduscopy was normal bilaterally.
Patient evaluation included a complete blood count with an elevated white blood cell count of 19.5 cells per microliter and platelet count of 516 platelets per microliter. Infectious etiologies including syphilis, Lyme disease, tuberculosis, HIV, and bacterial causes of endogenous endophthalmitis were excluded with the following normal tests: blood cultures, urinalysis with urine culture, Lyme titers, reactive plasma reagin, HIV, and a purified protein derivative tuberculin skin test. Erythrocyte sedimentation rate, rheumatoid factor, angiotensin-converting enzyme, HLA-B27, antineutrophilic cytoplasmic antibody panel, and anti-nuclear antibody panel were also unremarkable. Cerebrospinal fluid analysis showed no cells with normal glucose and protein levels. Computed tomography (CT) of the chest and brain was normal. Magnetic resonance imaging (MRI) of the brain and orbits revealed thickening of the orbital portion of the left optic nerve with enhancement of the optic nerve sheath (Fig. 1).
CT of the abdomen showed wall thickening of the ascending, transverse, and descending colon indicative of colitis (Fig. 2). The workup for infectious etiologies of colitis was negative. A flexible sigmoidoscopy showed subtle patches of granular mucosa in the rectum and sigmoid colon along with discrete ulcerations of the colonic mucosa. Biopsies from the rectum demonstrated acute inflammation and noncaseating granulomas confirming the diagnosis of CD.
The patient was treated with intravenous methylprednisolone (1 g daily for 1 week) followed by an oral prednisone taper, as well as oral mesalamine and corticosteroid eye drops. Two weeks after presentation, funduscopy revealed multifocal choroidal infiltrates in the left eye and mild left optic disc swelling (Fig. 3). Eight weeks after steroid therapy, these fundus findings resolved, and 3 months later, vision was 20/25, left eye, with mild dyschromatopsia, a central scotoma, and mild optic disc pallor. The patient was maintained on 5 mg of prednisone daily and mesalamine to treat CD.
CD is named after gastroenterologist Burrill Bernard Crohn, who in 1932 published a seminal case series of 14 patients with “regional ileitis” (1). It is now clear that CD can affect the entire GI tract although it typically causes acute and chronic transmural inflammation of the distal small intestine and proximal colon (1). Although UC shares some features with CD and falls under the rubric of IBD, the 2 are distinct pathological entities and usually distinguishable clinically. Both UC and CD now are considered systemic inflammatory conditions and may involve skin, joints, liver, kidneys, coagulation pathways, central nervous system, lungs, and eyes (1–3).
CD and UC are associated with a broad spectrum of ophthalmic involvement, including the optic nerve (4–7). This generally occurs in 4 clinical settings. First, CD-associated papillitis occurs with vitritis and/or anterior uveitis (8–10). Second, there are 5 documented cases of retrobulbar optic neuritis in patients with CD (10–13). In 2 cases, MRI findings were unremarkable with a favorable response to steroid therapy. Third, optic disc edema without clinical evidence of optic nerve dysfunction has been described with intermediate and posterior uveitis (14,15). Finally, patients with CD may develop idiopathic intracranial hypertension (15), in some possibly related to the use of systemic corticosteroids (16,17).
Our patient's optic nerve involvement with CD seems unique. He experienced acute vision loss in the left eye, and MRI findings were consistent with OPN. OPN is characterized by inflammation of the meninges surrounding the optic nerve (18). The development of steroid-responsive choroidal lesions and anterior chamber cell in our patient supports the diagnosis of an inflammatory process involving the uveal tract as well.
OPN is usually idiopathic and considered within the spectrum of nonspecific orbital inflammation (pseudotumor). On occasion, OPN can be linked to a specific cause, including sarcoidosis, giant cell arteritis, Wegener granulomatosis, tuberculosis, and syphilis (18–20). There is usually retention of good central visual acuity, although Purvin et al (18) reported that 3 of 14 patients with OPN initially had visual acuity of 20/300 or worse. Enhancement of the optic nerve meninges is found on contrasted neuroimaging studies, and patients with OPN experience good recovery of visual functions with steroids, provided that they are treated early in the clinical course (18).
It is unknown whether systemic treatment with anti-inflammatory medications, such as 5-aminosalicylic acid and corticosteroids, to reduce IBD flares also prevents optic nerve inflammation. Many reports of IBD-associated optic nerve inflammation, including our case, occur concurrently with GI exacerbations. It is plausible that control of GI disease may help prevent extraintestinal inflammatory manifestations of IBD. One noteworthy exception may be the use of tumor necrosis factor-alpha inhibitors. These biologic agents (infliximab, adalimumab, and etanercept) have been implicated in causing inflammatory, demyelinating events within the central nervous system (21), including the optic nerve (22–24).
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