Journal of Neuro-Ophthalmology, March 1984, Volume 4, Issue 1

Optic neuritis in inflammatory bowel disease.

It is not unusual for various ocular diseases to be associated with inflammatory bowel disease. Ocular involvement includes the inflammatory entities of keratitis, conjunctivitis, episcleritis, orbital pseudotumor, iritis and neuroretinitis , as well as those states in which the etiology remains undefined, i.e., scleromalacia perforans, peripheral corneal ulceration and furrow, retinal artery occlusion, and optic neuropathy. We report five cases of optic neuropathy associated with ulcerative colitis to emphasize that this may be the sole ocular manifestation of inflammatory bowel disease.

J. Clin. Neuro-ophthalmol. 4: 3-6, 1984. Optic Neuritis in Inflammatory Bowel Disease LYN A. SEDWICK, M.D.* TERENCE G. KLINGELE, M.D. RONALD M. BURDE, M.D. MYLES M. BEHRENS, M.D. Abstract It is not unusual for various ocular diseases to be associated with inflammatory bowel disease. Ocu­lar involvement includes the inflammatory entities of keratitis, conjunctivitis, episcleritis, orbital pseu­dotumor, iritis and neuroretinitis, as well as those states in which the etiology remains undefined, i.e., scleromalacia perforans, peripheral corneal ulcera­tion and furrow, retinal artery occlusion, and optic neuropathy. We report five cases of optic neuropa­thy associated with ulcerative colitis to emphasize that this may be the sole ocular manifestation of inflammatory bowel disease. Crohn reports an unusual complication of ul­cerative colitis in two women during severe at­tacks of diarrhea. 1 The report states that each patient was intensely photophobic and had pe­ripheral ulceration of the cornea. I Since 1925, these cases are often cited in the literature and usually are described as demonstrating corneal inflammation and iritis in association with ulcer­ative colitis. 2,3 In recent years, it is clear that ocular disease occurs with Crohn's disease or granulomatous ileocolitis in variety and fre­quency similar to that with ulcerative colitis.2-1o Many authors now refer to ulcerative colitis and Crohn's disease under the general rubric, "in­flammatory bowel disease," because of the diffi­culty in separating these two entities strictly into either ulcerative colitis or Crohn's disease in about 20% of casesll and because of similarity of the complications seen with the diseases.5,6, 11, 12 If one disregards eye pathology that seems only coincidentally found in patients with inflamma­tory bowel disease-like congenital cataracts and interstitial keratitis of luetic origin-the occur­rence of ocular disease related to in- From the Departments of Ophthalmology (LAS, TGK. RMB), Neurology, and Neurological Surgery (RMB), Washington University School of Medicine, St. Louis, Missouri; and the Institute of Ophthalmology (MMB), Columbia University, New York, New York. • Dr. Sedwick is currently in private practice in Orlando, Florida. March 1984 flammatorl bowel disease is around 2-5% of patients.2 - .13,14 Most frequently reported is iritis, which may occur in nearly 50% of patients who have arthritic involvement of the sacroiliac joint,2' 14 but episcleritis, conjunctivitis, and kera­titis are also reported with inflammatory bowel disease.2-5, 13 "Ischemic optic neuropathy" is also reported. 15 We report three cases of optic neuritis, one of recurrent papillitis with uveitis, and a case of neuroretinitis with retinal vasculitis in patients with ulcerative colitis. Case Reports Case 1 A 38-year-old woman experienced an acute decrease of vision in her left eye. Visual field testing showed an inferior arcuate paracentral scotoma in her left eye. There was blurring of the superior disc margin, and a diagnosis was made of optic neuritis. Initially, she was treated with 60 mg of oral prednisone/day, which was rapidly tapered over a 10-day period. Examination 14 days later revealed a visual acuity of 20/20 in each eye, but the inferior arcuate scotoma in her left visual field persisted. There was still blurring of the superior disc margin in this eye as well. Laboratory studies including complete blood count, antinuclear antibody test, lupus erythe­matosus preparation, protein electrophoresis, and serology were all negative or normal, and an erythrocyte sedimentation rate was 5 rnrn/hour. The patient reported an illness diagnosed as ul­cerative colitis several months prior to her episode of optic neuritis; this was treated with corticoste­roid enemas. Case 2 A 21-year-old woman had the acute onset of pain with movement of both eyes. The retroocular pain on the right side abated, but persisted on the left, and she noted a decrease of vision in her left eye 2 weeks later. Examination at that time re­vealed a visual acuity of 20/20 in the right eye and finger counting in the left. Kinetic perimetry demonstrated a central scotoma with an inferior 3 Inflammatory Bowel Disease altitudinal defect in her left visual field. There was mild pallor of the inferotemporal quadrant of the left optic disc. Optic canal views and skull x-rays were normal; complete blood count, anti­nuclear antibody test, and serology were normal. The erythrocyte sedimentation rate was 30 mm/ hour. The patient had known ulcerative colitis since age 9 years. She experienced only occasional flare-up of her bowel problem. She was treated with 80 mg of oral prednisone/day. Although her visual acuity improved to 20/20, she contin­ued to have relative color desaturation in her left eye. A relative afferent pupillary defect was also present. Case 3 A 26-year-old woman had a sudden loss of vision in her left eye associated with pain on movement of the globe. A diagnosis of optic neuritis was made, and she was treated with 60 mg of oral prednisone/day on a gradually taper­ing dose. High-resolution computerized tomog­raphy with orbital views, with and without con­trast agent, was normal. Examination 23 days later revealed a visual acuity of 20/20 in her right eye and "hand motions" in her left eye. Kinetic perimetry demonstrated a large central scotoma in her left visual field. Funduscopic examination revealed blurring of the nasal border of the left optic disc. The patient had a 9-year history of ulcerative colitis. Two weeks prior to her visual loss, she experienced a recrudescence of her bowel disease. This activation was treated suc­cessfully with sulfasalazine. Case 4 A 36-year-old women noted that the vision in her right eye was hazy. She had disc edema on the right and was advised to discontinue the use of her oral contraceptives. Examination several weeks later showed vision of 20/30 and 20/15 in her right and left eyes, respectively. There was an afferent pupillary defect and color desatura­tion on the right. Kinetic perimetry revealed an enlarged blind spot extending nearly to fixation. She had a mild anterior uveitis with 2+ cell and 1-2+ flare with fine keratic precipitates in her right eye. The right optic disc was edematous with several nerve fiber layer hemorrhages and cotton-wool spots. Skull x-rays, optic canal views, and chest x-ray were normal; complete blood count, antinuclear antibody test, lUpus erythe­matosus preparation, total complement levels, rheumatoid factor, serum protein electrophoresis, and serology were normal or negative, as were a neurologic examination and lumbar puncture. She was treated with 50 mg of oral prednisone/ day and a topical corticosteroid preparation for the right eye. The vision in her right eye improved to 20/20. The right disc was mildly atrophi~, and asymptomatic disc swelling was ~bserved m her left eye which resolved over a penod of 1 month. She was asymptomatic for 3 years when. she noted blurring of vision in her left eye assoClated with a fever and diarrhea. Examination 3 weeks later revealed a visual acuity of "finger counting" in her left eye. She had an anterior uveitis with 2+ cell and flare in the anterior chamber and an occasional cell in the anterior vitreous body. Mild pallor of the right disc was seen as well as mod­erate swelling of the left disc. Her erythrocyte sedimentation rate was 102 mm/hour. A barium enema revealed ulceration and atony of the colon compatible with a diagnosis of ulcerative colitis. Sulfasalazine was begun with subsequent reso­lution of her diarrhea and normalization of her erythrocyte sedimentation rate to 4 mm/hour within 2 months. Oral prednisone was added without effect, as her vision remained at a "fin­ger- counting" level. Case 5 A 40-year-old man presented with the com­plaint of decreased vision in his right eye. He had a known childhood amblyopia in his left eye. During a routine examination 2 years previously, he was found to have retinal telangiectasia with intraretinal hemorrhage and subretinal exudate, compatible with a diagnosis of Coat's disease. He was treated elsewhere with laser photocoagula­tion. Examination revealed a visual acuity of 20/ 25 in his right eye and "finger counting at several feet" in his left eye. Fundus examination showed bilateral disc edema. There were sheathing of arterioles, scattered intraretinal hemorrhages and cystOid macular edema in his right eye. Kinetic perimetry demonstrated a normal visual field on the right side and a large central scotoma on the left. The patient was known to have Crohn's disease, diagnosed by colonic biopsy 18 months previously. He was taking sulfasalazine for his bowel disease and was asymptomatic. Radi­ographic evaluation, with the exception of colonic diverticuli, was normal; however, on colonoscopy patchy areas of erythema were noted. Biopsy showed chronic mild inflammatory changes. The patient's antinuclear antibody test, histocompati­bility antigen-B27, and other collagen vascular laboratory studies were negative or normal, as were cerebrospinal fluid studies. He was treated with pulsed methylprednisolone followed by oral prednisone with improvement of his retinal vas­culitis, and the vision in his right eye improved to 20/20. Side effects of the steroid therapy ne­cessitated steroid withdrawal with a decrease in the vision in his right eye. Azathiaprine, chlor­ambucil, and indomethacin all were ineffective. Colchicine was tried, but not tolerated because of severe diarrhea. Journal of Clinical Neuro-ophthalmology Comment According to Kirsner and Shorter,II.12 inflam­matory bowel disease has an annual incidence of 4-6/100,000 and an incidence of 40-100/ 100,000.12 It occurs predominantly in industrial­ized countries. People who move from rural to urban areas incur a higher risk for the develop­ment of inflammatory bowel disease. 12 This dis­ease can occur in families and affects whites more often than .blac~s.12 Various environmental path­ogens are ImplIcated, but no clear association is found. 12 A number of autoimmune perturbations are found in patients with inflammatory bowel disease, but may be a consequence of the disease process itself. 12 The development of extraintes­tinaI manifestations of inflammatory bowel dis­ease is not yet linked definitively to the basic pathophysiologic process. 12 The literature concerning the complications and extraint~stinal . manifestations of inflammatory bowel dIsease IS extensive. Iritis and corneal dis­~ ase are documented to occur in patients with m~ammat.orybowel disease.2-5.12 In several large sene.s of mfl~mm.atory bowel disease patients, passmg mentIon IS occasionally made of rarer a.ssociat~~ ~cula~ diseases ~~ch as retrobulbar op­tic neuntis, orbItal myoSItis,4 and retinal artery occlusion.4Over the last several years, many well­documented cases of unusual ocular inflamma­t~ ry disease occurring with inflammatory bowel disease are described: 1) bilateral orbital myositis in a 14-y~ar-old boy who subsequently developed b~oody diarrhea and whose diagnosis of Crohn's disease was made from small bowel biopsyl6; 2) sc~eromalacia perforans in a 36-year-old man WIth an II-year history of ulcerative colitis and negative rheumatoid factor latex and antinuclear antibody, who resolved his eye lesion after total ~roctocolectomi7; 3) a characteristic elevated pe­npheral corneal opacity with subepithelial infil­trates seen in three patients with known Crohn's diseas~, ~hich ~n tum led to the diagnosis of C~ohn s disease In another patient who presented ~Ith eye symptoms and keratopathy only8; 4) bIlateral retinal branch arterial occlusion in a 34­ye~ r-old man with Crohn's disease reported in a s~nes of other patients with inflammatory bowel disease a~d cerebr~l t~rombosis6; 5) a 17-year­old bf1y WIth Crohn s disease status post resection of the terminal ileum and ascending colon, who ?eve~oped retinitis, papillitis and vitritis in con­Junction with a reactivation of his bowel disease7. and 6) a 24-year-old man with Crohn's diseas~ who developed uveitis in his right eye and bilat­eral optic neuropathy. 15 We d~scribe five cases of optic neuropathy to emphasIze the possibility of serious visual loss ~rom optic nerve involvement in patients with I~flammatory bowel disease. As in the two pre­vIOusly .well-d?c~mented cases,8.15 we see optic nerve disease m mflammatory bowel disease as March 1984 Sedwick, Klingele, Burde, Behrens part of the picture of generalized ocular inflam­mation (cases 4 and 5) and in isolation; i.e., three of our patients (cases 1, 2, and 3) have optic neuropathy without any associated findings of uveitis, retinitis, vitritis, or other ocular inflam­matory disease. This is the first report of optic n~uropathy in patients with inflammatory bowel dIsease occurring in the absence of other ocular inflammatory signs. Although the pathogenetic mechanism of inflammatory bowel disease is un­known, the ogtic neuritis resembles autoimmune optic neuritis 8 and supports the concept that the ocular inflammatory effects are mediated immu­nologically. This is consistent with the hypothesisl2 that the intestinal lesions of inflam­matory bowel disease are initiated by an external agent, possibly microbial, viral or dietary, and the ocular lesions represent epiphenomena which are mediated immunologically. . As in othe~ optic neuritides, therapeutic options In these patients are on less than solid ground. However, because corticosteroid therapy appears to ameliorate certain other manifestations of in­flammatory bowel disease, and we have had sim­ilar success in treating autoimmune optic neuri-tI. s, 18·It seems reasonable to treat these presumed cases of inflammatory optic neuropathy with cor­ticosteroids. Four of the five cases (1, 2, 4, and 5) show substantial improvement with this therapy. Some authors note a correlation between the occurrence of eye disease and "activity" of the bowel dise~se:J· 14.17 However, this relationship does not eXIst m our cases, with the exception of case 4. Resolution of ocular disease with colec­tomy or other surgery is reported, 13.19 and some advocate that the presence of severe iritis or other ocular disease is an indication for bowel resection in the management of severe intestinal disease. J·7 However, others note active eye disease in the face ?f apparent curative surgery for bowel dis­ease.- · J Only. a careful follow-up study specifi­cally addressmg the relationship between bowel resection for inflammatory bowel disease and extraintestinal manifestations will answer this question. Thus, all that is clear at this time is that certain ocul.ar disea~e.s, including optic neuritis, may oc­cur In the mIlIeu of mflammatory bowel disease. The optic neuritis appears to be corticosteroid­responsive if treatment is initiated early. References 1. Crohn, B.B.: Ocular lesions complicating ulcerative colitis. Am. J. Ophthalmol. 169: 260-267, 1925. 2. Hopkins, DJ, Horan, E., Burton, I.L., Clamp, S.E., de Dombal, FT, and Goligher, J.e.: Ocular disor­ders in a series of 332 patients with Crohn's dis­ease. Br. J. Ophthalmol. 58: 732-737,1974. 3. Korelitz, B.I., and Coles, R.5.: Uveitis associated with ulcerative and granulomatous colitis. Gastro­enterology 52: 78-82, 1967. 5 Inflammatory Bowel Disease 4. Greenstein, AJ., Janowitz, H.D., and Sachar, D.B.: The extraintestinal complications of Crohn's dis­ease and ulcerative colitis: A study of 700 patients. Medicine 55(4): 401-412, 1976. 5. Kirsner, J.B.: The local and systemic complications of inflammatory bowel disease. f. Am. Med. Assoc. 242: 1177-1183, 1980. 6. Schneiderman, J.H., Sharpe, J.A, and Sutton, D.M.C: Cerebral and retinal vascular complica­tions of inflammatory bowel disease. Ann. Neural. 5(4): 331-337,1979. 7. Macoul, K.L.: Ocular changes in granulomatous ileocolitis. Arch. Ophthalmol. 84: 95-97, 1970. 8. Knox, D.L., Snip, RC, and Stark, W.J.: The kera­topathy of Crohn's disease. Am. f. Ophthalmol. 90: 862-865, 1980. 9. Dekker-Saeys, B,J., Meuwissen, S.G.M., van den Berg-Loonen, E.M., deHaas, W.H.D., Agenant, D., and Tytgat, G.N.J.: Prevalence of peripheral ar­thritis, sacroilitis, and ankylosing spondilitis in pa­tient suffering from inflammatory bowel disease. Ann. Rheum. Dis. 37(1): 33-35, 1978. 10. Sauman, M.F., and Sugar, A: Peripheral corneal infiltrates in inflammatory bowel disease. Ann. Ophthalmol.13(1): 109-111, 1981. 11. Kirsner, J.B., and Shorter, RG.: Recent develop­ments in non-specific inflammatory bowel disease (first of two parts). N. Engl. f. Med. 306(13): 775­785, 1982. 12. Kirsner, J.B., and Shorter, RG.: Recent develop­ments in non-specific inflammatory bowel disease (second of two parts). N. Engl. f. Med. 306(14): 837­848, 1982. 13. Billson, F.A, deDombal, F.T., Watkinson, G., and Goligher, J.C: Ocular complications of ulcerative colitis. Gut8: 102-106,1967. 14. Wright, R., Lumsden, K., Luntz, M.H., Seve\, D., and Truelove, S.c.: Abnormalities of the sacro-iliac joints and uveitis in ulcerative colitis. Q. J. Med. 34: 229-236, 1965. 15. Heuer, D.K., Gager, W.E., and Reeser, F.H.: Is­chemic optic neuropathy associated with Crohn's disease.]. Clin. Neuro-ophthalmol.2: 175-181, 1982. 16. Young, RS., Hodes, B.L., Cruse, R.P., Koch, K.L., and Garovoy, M.R.: Orbital pseudotumor and Crohn's disease. f. Pediatrics 99(2): 250-252, 1981. 17. Tesar, P.J., Burgess, J.A., Goy, J.A.E., and Lazell, R.A: Scleromalacia perforans in ulcerative colitis. Gastorenterology 81: 153-155, 1981. 18. Dutton, J,J., Burde, R.M., and Klingele, T.G.: Au­toimmune retrobulbar optic neuritis. Am. J. Ophthalmol. 94: 11-17, 1982. 19. Knox, D.L.: Optic nerve manifestations of systemic diseases. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83: 743-750, 1977. Acknowledgment This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York (Department of Ophthalmology). Write for reprints to: Ronald M. Burde, M.D., Depart­ment of Ophthalmology-Box 8096, 660 South Euclid Avenue, St. Louis, Missouri 63110. Journal of Clinical Neuro-ophthalmology