Posterior Segment Manifestations of Inflammatory Bowel Disease BREIT B. ERNST, MD, CAREEN Y. LOWDER, MD, PhD, DAYID M. MEISLER, MD, FRONOE A. GUTMAN, MD
Abstract: Thirteen patients with inflammatory bowel disease and posterior segment disease were subject to a retrospective review. Eight patients had Crohn's disease and five had ulcerative colitis. In six patients, the inflammatory bowel disease was active when ocular inflammation occurred. Patients had one or more posterior segment findings that included serous retinal detachment (8), choroidal infiltrates (6), retrobulbar neuritis (1), papillitis (1), retinal pigment epithelium disturbance (1), and choroidal folds (1). Posterior segment disease responded to systemic and periocular corticosteroids in 9 of 13 cases. Four patients whose disease relapsed after corticosteroid therapy was suspended responded to bowel resection. Ophthalmologists should be aware of the wide spectrum of posterior segment abnormalities associated with inflammatory bowel disease that may require and respond to anti-inflammatory agents.
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Inflammatory bowel disease generally includes two disorders, Crohn's disease and ulcerative colitis. These disorders are often grouped together as inflammatory bowel disease because they are idiopathic inflammatory disorders of probable immune etiology and can be difficult to distinguish clinically.! Both can affect the colon and rectum and have similar extraintestinal manifestations involving the liver, skin, joints, and eye. In Crohn's disease, lymphocytic infiltrate and granulomatous inflammation involve the full thickness of the intestinal wall. Ulcerative colitis, however, is characterized by confluent superficial inflammation of the intestinal wall and the tissue infiltrate is comprised mainly of polymorphonuclear leukocytes. Ocular complications occur in 4% to 6% of patients with inflammatory bowel disease. 2-4 Posterior segment mani-
Originally received: October 28, 1990. Revision accepted: March, 5, 1991. From the Department of Ophthalmology, Cleveland Clinic Foundation, Cleveland. Presented at the American Academy of Ophthalmology Annual Meeting, Atlanta, Oct/Nov 1990. Reprint requests to Careen Y. Lowder, MD, PhD, Department of Ophthalmology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195-5024.
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festations are less common, but there have been case reports of posterior segment disease, including central serous choroidopathy,5,6 panuveitis,7 choroiditis,3,4 ischemic optic neuropathy,8 retinal vasculitis,8 neuroretinitis,9 and peripheral uveitis.1O In this article, 13 cases of posterior segment ocular inflammatory disease in patients with inflammatory bowel disease are reported_ A spectrum of abnormalities is described and include the unusual findings of serous retinal detachment associated with choroidal infiltrates and choroidal leaks.
MATERIALS AND METHODS Between January 1, 1971 and December 31, 1989, 1397 patients were entered into the Inflammatory Bowel Disease Registry at the Cleveland Clinic Foundation. Thirteen of these patients were referred to the Department ofOphthalmology because of visual complaints. Patients ranged in age from 15 to 67 years (mean, 35 years). Other causes of uveitis were excluded based on a thorough history, physical examination, and appropriate laboratory evaluations. The diagnosis of inflammatory bowel disease in this group was made 2 weeks to 17 years before ocular examination. Results of histopathologic examination of bowel biopsy specimens showed full-thickness lympho-
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Table 1. Clinical Profiles Patient No./Age (yrs) Sex
Duration/ Type* /Activity IBD
Extraintestinal Disorders
Onset/Symptoms
Initial Visual Acuity
Clinical/Angiographic Findings
1/28/F
4 yrs/C/Yes
No
1 wk/decreased VA, headache
20/15 HM
2/25/F
1 yr/C/No
No
3 wks/blurred VA aD, headache
20/25 20/25
3/56/F
5 yrs/C/No
Recurrent arthritis (shoulder) iritis
Decreased VA
20/80 20/200
4/27/F
1 yr/U/Yes
Erythema nodosum; arthritis elbows, knees
10 days/headache, fever, myalgia, arthalgia, blurred VA
20/25 20/25
5/15/M
2 wks/C/Yes
No
5 days/dark spot VA as
6/43/M
13 yrs/C/No
Arthritis, knees
Sudden/decreased VA au
20/20 20/25 20/40 20/30
7/20/M
1 yr/C/Yes
No
2 mas/decreased VA au
20/70 20/25
8/40/F
17 yrs/U/No
No
t /Blurred VA, photophobia
20/20 20/20
9/67/M
9 yrs/U/No
t/distortion of VA
20/20 20/20
10/40/M
5 yrs/U/Yes
Arthritis; ankles, knees wrists; eczematoid dermatitis, iritis Atypical dermatitis, herpetiform is
1 mo/headache, photophobia, blurred VA
20/40 20/50
11/22/M
8 yrs/C/No
Iritis
5 mas/decreased VA
12/49/M
2 yrs/U/Yes
No
6 mas/blurred VA
6/200 20/60 20/20' 20/30
Multifocal choroidal infiltrates and SRD temporal to maCula aU/choroidal lesions blocked fluorescein in early phases and had late staining Multifocal choroidal infiltrates and SRD aD RPE disturbance macula au, SRD as/ choroidal leak within SRD
13/20/F
4 yrs/C/No
No
1 mo/blurred VA
20/20 20/20
Large SRD aD/choroidal leak within SRD
APD as, multifocal yellow choroidal lesions; multifocal SRD aU/choroidal lesions blocked fluorescein in early phases and accumulated fluorescein within areas of SRD APD aD, abnormal color testing aD, peripapillary cells; CSF lymphocytosis Marked RPE atrophy extending inferiorly from the optic nerve in wedged shaped pattern, as, bone spicule formation as Iritis, au multifocal yellow choroidal lesions some with hemorrhage/ choroidal lesions blocked fluorescein early and stained in late phases SRD in macula as/choroidal leak within area of SRD SRD aD, multiple RPE detachments as/choroidal leak 00, multiple RPE detachments as Iritis au, optic nerve hyperemia au, multifocal choroidal infiltrates and RPE disturbance au +APD as, iritis as, vitreitis au, marked elevation of the optic nerve as with surrounding SRO/vascular congestion and staining of the optic nerve Iritis as, choroidal lesions, choroidal folds aU/cystoid macular edema choroidal folds
IBD = inflammatory bowel disease; C = Crohn's disease; VA = visual acuity; HM = hand motions; APD = afferent pupillary defect; as retinal detachment; au = both eyes; aD = right eye; CSF = cerebrospinal fluid; U = ulcerative colitis, RPE = retinal pigment epithelium. * Type of inflammatory bowel disease. t Onset not recorded.
cytic inflammation and granulomas, establishing the diagnosis ofCrohn's disease in five patients (cases 1,2,3, 6, and 7). In four patients (cases 4, 8, 10, and 12), biopsy specimens had confluent superficial mucosal neutrophilic inflammation involving the rectum or colon consistent with ulcerative colitis. Narrowing of the terminal ileum and "skip" lesions were present on barium swallow, suggesting Crohn's disease in three patients (cases 5, 11, and 13). In one patient (case 9), loss of haustra and irregular thickened mucosa on barium enema suggested ulcerative colitis.
Systemic Steroid Response/ Other
Final Visual Acuity
Yes/no
20/20 20/20
Yes/no
20/20 20/20
None
20/80 20/200
Yes/no
20/20 20/20
Yes/no
20/20 20/40 20/15 20/20
Yes/laser Yes/bowel surgery
20/30 20/20
No/no
20/25 20[25
No/no
20/20 20/25
Yes/bowel surgery
20/20 20/25
Yes/no
20/30 20/60 20/20 20/20
No/laser bowel surgery Yes/bowel surgery =
left eye; SRD
20/30 20/20 =
serous
RESULTS The posterior segment findings in this group of patients included serous retinal detachment, choroidal infiltrates, retrobulbar neuritis, papillitis, retinal pigment epithelium (RPE) disturbance, and choroidal folds. The demographic characteristics and clinical profiles of the 13 patients are presented in Table 1. Table 2 summarizes the posterior segment complications found in this group of patients. The following case reports are representative of the clinical 1273
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Table 2. Posterior Segment Findings in Thirteen Patients with Inflammatory Bowel Disease Findings Serous retinal detachment with Choroidal infiltrates RPE leak Papillitis Choroidal infiltrates without serous retinal detachment Retrobulbar neuritis Choroidal folds
No. of Patients
Case No.
8 3 4 1
1, 5, 6, 8, 10-13 1,10,11 5,6, 12, 13 8
3 1 1
4, 7, 9 2 9
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roidal infiltrates were found temporal to the macula (Figs 4, 5). Figures 6A, B, and C demonstrate the fluorescein angiographic findings. Prednisone (100 mg daily) was started. The patient had a dramatic response to systemic steroid therapy showing complete resolution of the bilateral serous detachments within 24 hours. The ocular signs and symptoms recurred several time as steroids were tapered. The patient finally underwent bowel resection. There have been no recurrences of eye disease in a 14year follow-up.
CHOROIDAL INFILTRATES
course of the most common posterior segment manifestations seen in our patients: choroidal infiltrates with or without overlying serous retinal detachment and choroidal leaks with overlying serous retinal detachment.
CASE REPORTS CHOROIDAL INFILTRATES WITH OVERLYING SEROUS RETINAL DETACHMENT Case 1. A 28-year-old woman complained of decreased vision in her left eye and headache for I week. Four years previously, the patient was diagnosed with Crohn's disease. She was maintained on sulfasalazine (Azulfidine), and a single recurrence of Crohn's disease occurred 6 months before her current symptoms. Her visual acuity was 20/15 in the right eye and hand motions in the left. The left eye had an afferent pupillary defect. The anterior chambers were quiet. Bilateral, muItifocal, yellowish choroidal lesions were scattered in the posterior poles within areas of overlying serous retinal detachments. In the left eye, localized areas of serous retinal detachments were seen in the macula, temporal arcades (Fig I), and nasal to the disc (Fig 2). Fluorescein angiographic findings of the left eye are presented in Figures 3A, B, and C. The right eye was similar but had a larger area of shallow confluent serous retinal detachment. Oral prednisone (80 mg daily) was begun. One week later, visual acuity in the left eye improved to 20/40 with partial resolution of the serous retinal detachment. Systemic steroids were discontinued after being tapered over 3 weeks. Visual acuity returned to 20/20, and the serous retinal detachments and choroidal infiltrates resolved with minimal retinal pigment epithelial disturbance. Case 10. A 40-year-old man presented with a 4-week history of blurred vision, frequent diarrheal stools, left lower quadrant cramps, and bilateral frontal and retro-orbital headache. Six years before, the patient presented with generalized erythematous, raised pruritic eruption, a history of bloody stools, and many small, whitish vesicles on the oral mucosa. Results of sigmoidoscopy showed ulcerative colitis. His atypical dermatitis herpetiformis, colitis, and aphthous stomatitis responded to a brief regiment of systemic corticosteroids. Visual acuity was 20/40 in the right eye and 20/50 in the left. The anterior segments were quiet. Multifocal, yellowish choroidal lesions with indistinct borders measuring approximately '16 disc diameter in size were scattered throughout the posterior pole. Bilateral localized serous retinal detachments overlying the cho-
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Case 7. A 20-year-old man with active Crohn's disease had decreased vision in both eyes for 2 months' duration. Visual acuity was 20170 in the right eye and 20/25 in the left. The anterior chambers had 2+ cells and flare and there was moderate bilateral vitreitis. Multifocal, yellowish choroidal lesions measuring Vs disc diameter in size were widely distributed throughout the posterior segments, and in some areas they were confluent (Figs 7A, B). The change in the clinical appearance of the choroidallesions was documented over several weeks. The early, active lesions were yellowish with hazy, soft, indistinct borders. The active lesions blocked fluorescein in the choroidal phase and stained in the late phases (Figs 8A, B). As the choroidal lesion aged, sharp borders developed, which were associated with retinal pigment epithelial disturbance and choroidal scarring. Prednisone (100 mg daily) was begun. Within 3 weeks, visual acuity improved to 20/30 in the right eye and 20/20 in the left. Tapering of steroids resulted in a recurrence of choroiditis associated with a flare ofCrohn's disease. The terminal ileum and ascending colon were resected. No new choroidal lesions developed after the surgery, but the patient continued to have recurrent iritis and mild recurrences of his bowel disease. Finally an active focus of Crohn's disease in the rectal region was treated successfully and the bowel disease and uveitis remitted at the same time. This patient has not had a recurrence in 5 years of follow-up. Case 4. A 27-year-old woman presented with a to-day history of blurred vision, headache, fever, generalized myalgia, arthralgia, and diarrhea. A painful eruption consistent with erythema nodosum was noted on the left pretibial area. Subtotal colectomy confirmed the diagnosis of ulcerative colitis 1 year previously. Visual acuity was 20/25 in both eyes. The conjunctiva and episclera were injected bilaterally. The right anterior chamber had 1+ cell and flare and the left anterior chamber had 3+ cells and 1+ flare. Multifocal, yellowish-white choroidal lesions were present bilaterally (Fig 9). In this particular case, the choroidal infiltrates in the midperiphery had a more homogeneous and slightly thickened appearance. Choroidal hemorrhages were present along the borders of the lesions (Fig 10). The fluorescein angiographic findings are demonstrated in Figures 11 A and B. Topical steroids and cycloplegics were instituted. Systemic steroids were withheld pending laboratory evaluation. Two weeks later, the anterior segment inflammation was almost resolved. Choroidal lesions of various ages and in various stages of activity were noted in the posterior segments of both eyes as described in the previous case report (case 7). Active choroidal lesions had indistinct borders and demonstrated blockage of fluorescein in the early phases and older inactive lesions had sharp borders and less blockage of fluorescein in the arteriovenous phase. Focal sheathing of blood vessels was noted in both eyes and new choroidallesions developed in the left macula. Over the next 4 weeks, new choroidal infiltrates continued to appear as others became inactive, and further nodular eruptions were discovered on her legs. At this point, proctoscopy demonstrated pouchitis and a
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Fig 1. Top left, case I. Localized serous retinal detachments in the macula (between large arrows) and temporal arcades (small arrows), of the left eye. Fig 2. Top right, case I. Localized serous retinal detachment (between arrows) nasal to the left disc. Fig 3. Case I. Early, middle, and late phases of the angiogram document multifocal choroidal lesions, which block fluorescein in the early phase (center l eft , A), develop confluence of staining (center right, B), and accumulate fluorescein within the area of serous retinal detachment in the late frames (bottom left , C). Fig 4. Bottom right, case 10. Serous retinal detachment was present in the macula (between arrows) of the right eye.
perianal abscess. Prednisone, 15 mg daily, was initiated. Two weeks later, visual acuity returned to 20/20 in both eyes and no new choroidal lesions were noted. After remission, multifocal atrophic choroidal scars were evident in the posterior pole. The patient has not had a recurrence in 2 years of follow-up.
SEROUS RETINAL DETACHMENT AND CHOROIDAL LEAKS
Case 12. A 49-year-old man had active bowel disease when he presented with a 2-week history of blurred vision in his left
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Fig 5. Top left. case 10. Localized serous retinal detachment (between arrows) overlying choroidal infiltrates temporal to the right macula. Fig 6. Case 10. Early, middle, and late phases of the angiogram demonstrate blocking of fluorescein by the choroidal infiltrates in the early phase (top righI, A), staining of the lesions (cenler left, B), and accumulation of fluorescein within the area of overlying serous retinal detachment (center right, C). Fig 7. Case 7. Multifocal choroidal lesions of various ages scattered in the posterior pole. The early, acute lesions have indistinct borders (large arrows). The older, inactive lesions have sharp borders (small arrows) and are associated with retinal pigment epithelium disturbance and scarring (boltom left, A). In some areas the choroidal lesions were confluent (between arrows) (boltom right, B).
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Fig 8. Case 7. The active lesions blocked fluorescein in the early phases (left, A) and stained in the late phases (right, B).
eye. A diagnosis of ulcerative colitis was made 2 years previously from results of a biopsy specimen. He was maintained on azulfidine and prednisone. The dosage of prednisone had just been decreased from 30 mg to 20 mg when the visual symptoms developed. Visual acuity was 20/20 in the right eye and 20/30 in the left. Both maculae had marked pigmentary disturbance. There were three focal areas of paramacular serous retinal detachment in the left eye (Fig 12). Results of fluorescein angiography showed multifocalleaks from the choroid within the areas of serous retinal detachment (Figs 13A, B). The patient had focal photocoagulation treatment to the areas of leakage. The serous retinal detachment nasal to the fovea persisted and new areas of focal serous retinal detachment were identified 5 months later, and the patient received additional photocoagulation. During this period of observation, the ulcerative colitis remained active with active mucosal fissures in the rectum. After 8 months, the bowel disease became quiescent with complete resolution of the serous retinal detachment. There have been no recurrences.
DISCUSSION This study describes 13 patients with posterior segment manifestations associated with inflammatory bowel disease. A spectrum of findings resulting from ocular inflammation involving the choroid and the optic nerve are reported. Choroidal infiltrates were the most common findings. Six patients (cases I, 4, 7, 9, 10, and 11). had multifocal, yellow-white choroidal infiltrates. The infiltrates were bilateral in five of six patients. The lesions appeared most often in the posterior pole. They measured less than 112 disc diameter and, in some patients, they were confluent. Acute, active lesions had soft, indistinct borders. Systemic corticosteroid therapy rapidly induced remission in the choroidal lesions resulting in atrophic or hyperpigmented scars. Untreated lesions healed spontaneously (case 4) but new lesions continued to form until systemic corticosteroids were instituted. The nature of these infiltrates is uncertain, but histopathologic studies of an eye enucleated with panuveitis from a patient with Crohn's disease demonstrated choroidal granulomas. 7
However, choroidal granulomas are an unlikely explanation for choroidal infiltrates occurring in patients with ulcerative colitis because granulomas are not part of the intestinal disorder. In heavily involved areas or areas of confluent choroidal infiltrates, serous retinal detachments were commonly identified. Results of fluorescein angiography showed the acute or early choroidal lesions blocked fluorescein in the early phases of the angiogram and developed late staining. A similar pattern has been described for other disorders. Acute multi focal placoid pigment epitheliopathy has subretinal infiltrates with a similar angiographic appearance. Lesions similar to acute multifocal placoid pigment epitheliopathy have been reported in regional enteritis. II These lesions are grayish, involving the RPE, and heal with diffuse pigmentary disturbance. Further, serous retinal detachment seen in three of our patients with choroidal infiltrates is an uncommon occurrence in acute multifocal placoid pigment epitheliopathy.12 Multiple evanescent white dot syndrome has white infiltrates with a different angiographic appearance that do not scar.12 Choroidal lesions also occur in syphilis and tuberculosis, but serology or skin testing did not support these diagnoses in our patients. Sarcoidosis, sympathetic ophthalmia, and Harada's disease can cause focal choroidal infiltrates, but our patients did not have clinical findings suggestive of these diseases. Posterior scleritis has been reported in patients with inflammatory bowel disease,5,13 and choroidal infiltrates can be seen overlying a choroidal mass in posterior scleritis. 12- 14 Ultrasonography was not performed in our patients, and an associated posterior scleritis can not be excluded in cases 1,4, 7, 9, 10, and 11. Bilateral choroidal folds were present in one patient. These folds were demonstrated on two successive fluorescein angiograms taken several weeks apart and resolved spontaneously. There was no hypotony, papilledema, or choroidal mass when the choroidal folds were observed. A similar angiographic pattern has been reported in patients with benign lymphoid hyperplasia and lymphocytic 1277
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Fig 9. Top left, case 4. Early (active) multifocal choroidal lesions in left macula. Fig 10. Top right, case 4. Choroidal infiltrates in the midperiphery have a more homogeneous and thickened appearance, associated with choroidal hemorrhages. Fig 11. Center, case 4. Active choroidal lesions block fluorescein in the early phase of the angiogram (left, A) and stain in the late phases (right, B). Fig 12. Bottom, case 12. Focal serous retinal detachments (small arrows) in the paramacular region and temporal to the left disc (large arrows).
infiltration ofthe choroid. 15 The mechanism for choroidal folds in our patient is uncertain. In addition to choroidal folds, this patient had multifocal choroidal infiltrates in
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one eye. A more diffuse cellular infiltration in addition to the focal choroidal infiltrates may have caused thickening of the choroid resulting in choroidal folds.
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Fig 13. Case 12. Fluorescein angiography shows focal areas of hyperfluorescence within the paramacular and peripapillary areas in the early arteriovenous phase (left, A). These areas increase in intensity and late staining develops at the temporal edge of the disc within the area of serous retinal detachment and three discrete choroidal leaks are seen within the serous retinal detachment in the paramacular area (right, 8).
Papillitis was present in two patients and has been previously reported in association with inflammatory bowel disease by Macoul9 and Heuer et al. 8 Their patients were young men with Crohn's disease who had severe bilateral optic nerve involvement resulting in neuroretinitis9 and ischemic optic nerve damage. 8 Our patients (cases 2 and 8) also had Crohn's disease but were young women with unilateral optic nerve involvement and good vision. Retrobulbar neuritis in case 2 was mild and was characterized by a relative afferent pupillary defect, abnormal color testing, and a normal field. Case 8 had marked elevation of the left optic nerve with associated relative afferent pupillary defect and serous retinal detachment. Both patients had resolution of their optic nerve inflammation without sequelae. Permanent arcuate field defects have occurred in previously reported cases, despite treatment with systemic corticosteroids. 8 Cerebrospinal fluid lymphocytosis present in case 2 suggests that a similar type of infiltration may be occurring in the optic nerves of these patients. Four of our patients had serous retinal detachments and choroidal leaks (cases 5, 6, 12, and 13). These complications have been associated with inflammatory bowel disease. 5,6 These serous retinal detachments with choroidal leaks have the same characteristics as idiopathic central serous choroidopathy originally described by GasS. 16 Gass was careful to differentiate idiopathic central serous choroidopathy from juvenile disciform degeneration, which is an inflammatory disorder with a positive test for histoplasmosis.1 6 Two of our patients had choroidal leaks with an overlying serous retinal detachment that resolved with systemic corticosteroids alone, suggesting that central serous choroidopathy in patients with inflammatory bowel disease also may be inflammatory in nature. Laser therapy has previously been used to treat central serous choroidopathy in inflammatory bowel disease6 and was effective in treating central serous choroidopathy in two of our patients (cases 6 and 12). Systemic corticosteroid therapy should be tried before laser photocoagulation is undertaken in these patients.
Understanding ocular manifestations of inflammatory bowel disease is difficult since the pathogenesis of the intestinal disorder is unclear. Infectious causes are poorly supported by cultures, electron microscopy, transmissibility, or response to antibiotics. Although Mycobacterium paratuberculosis has been isolated in cultures of biopsy specimens obtained from patients with inflammatory bowel disease,17 it is an inconsistent finding and is often present in normal populations. Genetic factors may play a role in the pathogenesis of inflammatory bowel disease. There is an increased incidence of disease in Ashkenazi Jews and first-degree relatives. Further, patients with inflammatory bowel disease with spondylitis have a higher incidence of the HLA-B27 antigen. Immune pathogenesis is suggested by histologic and humoral alterations. Increased populations of intestinal lymphocytes occur in inflammatory bowel disease. Intestinal plasma cell numbers increase with active disease. Tcell subtypes are normal, but a loss of normal T -suppressor response occurs during active disease. I Circulating anticolonic epithelial antibodies are seen, which result in Tcell-mediated cytolysis. 18 The incidence of anticolonic epithelial antibodies also is increased in family members. 19 The extraintestinal manifestations of inflammatory bowel disease are well recognized and include liver, skin, eye, and joint disease. Migratory arthralgias20 and ocular and skin manifestations typically occur when intestinal disease is active. I Activation of abnormal intestinal immunity in inflammatory bowel disease may result in circulating antibodies or antigen-antibody complexes21 that can mediate extraintestinal complications. Inflammatory bowel disease was active in 50% of our patients when posterior segment abnormalities were observed. Resection of the actively inflamed bowel reduces and often leads to resolution of extraintestinal manifestations in the eyes, skin, and joints. 2 In four of our patients (cases 7, 10, 12, and 13) bowel resection was temporally related to the resolution of their eye disease. The incidence of arthritis, pericholangitis, and skin disorders are signif1279
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icantly reduced in patients with inflammatory bowel disease patients who are taking corticosteroids. 22 Systemic corticosteroid treatment also appears to have an effect on ocular posterior segment disease. In case 12, systemic corticosteroid had been reduced immediately before the onset of posterior segment disease. Nine of 13 patients' posterior segment disorders responded rapidly to systemic corticosteroid treatment. Case 4 had coincident resolution of her eye disease when oral prednisone was taken for pouchitis and perianal abscess. Posterior segment manifestations of inflammatory bowel disease have not been commonly recognized. 3- 10 In our series, it also appears that the incidence of posterior segment manifestations is low, being less than 1% of patients with inflammatory bowel disease at our institution. This low incidence also may be attributed to the frequent use of corticosteroids in inflammatory bowel disease22 and the rapid resolution of posterior segment manifestations with systemic corticosteroid therapy. Coincidental ocular inflammation may have resulted in focal choroidal leaks and optic neuritis. In our patients with focal choroidal leaks, a high incidence of concurrent active bowel disease and improvement of ocular disease associated with bowel resection in two patients suggests that the disorders may be related. It is hoped that this report will lead to an increased recognition of posterior segment complications associated with inflammatory bowel disease; with a heightened awareness, ophthalmologists will be better guided toward diagnosis and management of this group of eye findings.
REFERENCES 1. Strober W, James SP. The immunologic basis of inflammatory bowel disease. J Clin Immunol1986; 6:415-32. 2. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's di~ease and ulcerative colitis: a study of 700 patients. Medicine 1976; 55:401-12. 3. Hopkins OJ, Horan E, Burton IL, et aI. Ocular disorders in a series of 332 patients with Crohn 's disease. Br J Ophthalmol1974; 58:732-7. 4. Billson FA, De Dombal FT, Watkins G, Goligher JC. Ocular complications of ulcerative colitis. Gut 1967; 8:1 02-6.
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5. Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn's disease. Ophthalmology 1984; 91:163-73. 6. Kaneko E, Nawano N, Honda N, et al. Ulcerative colitis complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment. Dig Dis Sci 1985; 30:896-900. 7. Salmon JF, Wright JP, Bowen RM, Murray AD. Granulomatous uveitis in Crohn's disease. A clinicopathologic case report Arch Ophthalmol 1989; 107:718-9. 8. Heuer OK, Gager WE, Reeser FH. Ischemic optic neuropathy associated with Crohn's disease. J Clin Neuro-Ophthalmol 1982; 2:1 7581. 9. Macoul KL. Ocular changes in granulomatous ileocolitis. Arch Ophthalmol1970; 84:95-7. 10. Zaidman GW, Coles RS. Peripheral uveitis and ulcerative colitis. Ann Ophthalmol 1981; 13:73-6. 11. Gass JDM. Acute posterior multifocal placoid pigment epitheliopathy: a long-term follow-up study. In: Fine SL, Owens SL, eds. Management of Retinal Vascular and Macular Disorders. Baltimore: 1983 Williams & Wilkins 1983; 176. 12. Gass JDM. Stereoscopic Atlas of Macular Diseases. Diagnosis and Treatment, 3rd ed. St. Louis: CV Mosby Co, 1987. 13. Benson WE. Posterior scleritis. Surv OphthalmoI1988; 32:297-316. 14. Benson WE, Shields JA, Tasman W, Crandall AS. Posterior scleritis: a cause of diagnostic confusion . Arch Ophthalmol1979; 97:1482-6. 15. Desroches G, Abrams GW, Gass JD. Reactive lymphoid hyperplasia of the uvea: a case with ultrasonographic and computed tomographic studies. Arch Ophthalmol1983; 101 :725-8. 16. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol 1967; 63:587-615. 17. Hodgson HJF, Jewel DP. Immunology of inflammatory bowel disease. Baillieres Clin Gastroenterol1987; 1531-45. : 18_ Auer 10, Grosch L. HardOrfer C, ROder A. Ulcerative colitis specific cytotoxic IgG autoantibodies against colonic epithelial cancer cells. Gut 1988; 29:1639-47. 19. Fiocchi C, Roche JK, Michener WM. High prevalence of antibodies to intestinal epithelial antigens in patients with inflammatory bowel disease and their relatives. Ann Intem Med 1989; 110:786-94. 20. Donaldson RM. Crohn's Disease. In: Sieisenger MH, Fordtran JS, eds. Gastrointestinal Disease, 4th ed. Philadelphia: WB Saunders, 1989; vol. 1, chap. 71. 21 . Hodgson HJF, Potter BJ, Jewell DP. Immune complexes in ulcerative colitis and Crohn's disease. Clin Exper ImmunoI1977; 29:187-96. 22. Kemler BJ, Alpert E. Inflammatory bowel disease: study of cell mediated cytotoxicity for isolated human colonic epithelial cells. Gut 1980; 21 ;353-9.
Abstract: Thirteen patients with inflammatory bowel disease and posterior segment disease were subject to a retrospective review. Eight patients had Crohn's disease and five had ulcerative colitis. In six patients, the inflammatory bowel disease was active when ocular inflammation occurred. Patients had one or more posterior segment findings that included serous retinal detachment (8), choroidal infiltrates (6), retrobulbar neuritis (1), papillitis (1), retinal pigment epithelium disturbance (1), and choroidal folds (1). Posterior segment disease responded to systemic and periocular corticosteroids in 9 of 13 cases. Four patients whose disease relapsed after corticosteroid therapy was suspended responded to bowel resection. Ophthalmologists should be aware of the wide spectrum of posterior segment abnormalities associated with inflammatory bowel disease that may require and respond to anti-inflammatory agents.
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Inflammatory bowel disease generally includes two disorders, Crohn's disease and ulcerative colitis. These disorders are often grouped together as inflammatory bowel disease because they are idiopathic inflammatory disorders of probable immune etiology and can be difficult to distinguish clinically.! Both can affect the colon and rectum and have similar extraintestinal manifestations involving the liver, skin, joints, and eye. In Crohn's disease, lymphocytic infiltrate and granulomatous inflammation involve the full thickness of the intestinal wall. Ulcerative colitis, however, is characterized by confluent superficial inflammation of the intestinal wall and the tissue infiltrate is comprised mainly of polymorphonuclear leukocytes. Ocular complications occur in 4% to 6% of patients with inflammatory bowel disease. 2-4 Posterior segment mani-
Originally received: October 28, 1990. Revision accepted: March, 5, 1991. From the Department of Ophthalmology, Cleveland Clinic Foundation, Cleveland. Presented at the American Academy of Ophthalmology Annual Meeting, Atlanta, Oct/Nov 1990. Reprint requests to Careen Y. Lowder, MD, PhD, Department of Ophthalmology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH, 44195-5024.
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festations are less common, but there have been case reports of posterior segment disease, including central serous choroidopathy,5,6 panuveitis,7 choroiditis,3,4 ischemic optic neuropathy,8 retinal vasculitis,8 neuroretinitis,9 and peripheral uveitis.1O In this article, 13 cases of posterior segment ocular inflammatory disease in patients with inflammatory bowel disease are reported_ A spectrum of abnormalities is described and include the unusual findings of serous retinal detachment associated with choroidal infiltrates and choroidal leaks.
MATERIALS AND METHODS Between January 1, 1971 and December 31, 1989, 1397 patients were entered into the Inflammatory Bowel Disease Registry at the Cleveland Clinic Foundation. Thirteen of these patients were referred to the Department ofOphthalmology because of visual complaints. Patients ranged in age from 15 to 67 years (mean, 35 years). Other causes of uveitis were excluded based on a thorough history, physical examination, and appropriate laboratory evaluations. The diagnosis of inflammatory bowel disease in this group was made 2 weeks to 17 years before ocular examination. Results of histopathologic examination of bowel biopsy specimens showed full-thickness lympho-
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Table 1. Clinical Profiles Patient No./Age (yrs) Sex
Duration/ Type* /Activity IBD
Extraintestinal Disorders
Onset/Symptoms
Initial Visual Acuity
Clinical/Angiographic Findings
1/28/F
4 yrs/C/Yes
No
1 wk/decreased VA, headache
20/15 HM
2/25/F
1 yr/C/No
No
3 wks/blurred VA aD, headache
20/25 20/25
3/56/F
5 yrs/C/No
Recurrent arthritis (shoulder) iritis
Decreased VA
20/80 20/200
4/27/F
1 yr/U/Yes
Erythema nodosum; arthritis elbows, knees
10 days/headache, fever, myalgia, arthalgia, blurred VA
20/25 20/25
5/15/M
2 wks/C/Yes
No
5 days/dark spot VA as
6/43/M
13 yrs/C/No
Arthritis, knees
Sudden/decreased VA au
20/20 20/25 20/40 20/30
7/20/M
1 yr/C/Yes
No
2 mas/decreased VA au
20/70 20/25
8/40/F
17 yrs/U/No
No
t /Blurred VA, photophobia
20/20 20/20
9/67/M
9 yrs/U/No
t/distortion of VA
20/20 20/20
10/40/M
5 yrs/U/Yes
Arthritis; ankles, knees wrists; eczematoid dermatitis, iritis Atypical dermatitis, herpetiform is
1 mo/headache, photophobia, blurred VA
20/40 20/50
11/22/M
8 yrs/C/No
Iritis
5 mas/decreased VA
12/49/M
2 yrs/U/Yes
No
6 mas/blurred VA
6/200 20/60 20/20' 20/30
Multifocal choroidal infiltrates and SRD temporal to maCula aU/choroidal lesions blocked fluorescein in early phases and had late staining Multifocal choroidal infiltrates and SRD aD RPE disturbance macula au, SRD as/ choroidal leak within SRD
13/20/F
4 yrs/C/No
No
1 mo/blurred VA
20/20 20/20
Large SRD aD/choroidal leak within SRD
APD as, multifocal yellow choroidal lesions; multifocal SRD aU/choroidal lesions blocked fluorescein in early phases and accumulated fluorescein within areas of SRD APD aD, abnormal color testing aD, peripapillary cells; CSF lymphocytosis Marked RPE atrophy extending inferiorly from the optic nerve in wedged shaped pattern, as, bone spicule formation as Iritis, au multifocal yellow choroidal lesions some with hemorrhage/ choroidal lesions blocked fluorescein early and stained in late phases SRD in macula as/choroidal leak within area of SRD SRD aD, multiple RPE detachments as/choroidal leak 00, multiple RPE detachments as Iritis au, optic nerve hyperemia au, multifocal choroidal infiltrates and RPE disturbance au +APD as, iritis as, vitreitis au, marked elevation of the optic nerve as with surrounding SRO/vascular congestion and staining of the optic nerve Iritis as, choroidal lesions, choroidal folds aU/cystoid macular edema choroidal folds
IBD = inflammatory bowel disease; C = Crohn's disease; VA = visual acuity; HM = hand motions; APD = afferent pupillary defect; as retinal detachment; au = both eyes; aD = right eye; CSF = cerebrospinal fluid; U = ulcerative colitis, RPE = retinal pigment epithelium. * Type of inflammatory bowel disease. t Onset not recorded.
cytic inflammation and granulomas, establishing the diagnosis ofCrohn's disease in five patients (cases 1,2,3, 6, and 7). In four patients (cases 4, 8, 10, and 12), biopsy specimens had confluent superficial mucosal neutrophilic inflammation involving the rectum or colon consistent with ulcerative colitis. Narrowing of the terminal ileum and "skip" lesions were present on barium swallow, suggesting Crohn's disease in three patients (cases 5, 11, and 13). In one patient (case 9), loss of haustra and irregular thickened mucosa on barium enema suggested ulcerative colitis.
Systemic Steroid Response/ Other
Final Visual Acuity
Yes/no
20/20 20/20
Yes/no
20/20 20/20
None
20/80 20/200
Yes/no
20/20 20/20
Yes/no
20/20 20/40 20/15 20/20
Yes/laser Yes/bowel surgery
20/30 20/20
No/no
20/25 20[25
No/no
20/20 20/25
Yes/bowel surgery
20/20 20/25
Yes/no
20/30 20/60 20/20 20/20
No/laser bowel surgery Yes/bowel surgery =
left eye; SRD
20/30 20/20 =
serous
RESULTS The posterior segment findings in this group of patients included serous retinal detachment, choroidal infiltrates, retrobulbar neuritis, papillitis, retinal pigment epithelium (RPE) disturbance, and choroidal folds. The demographic characteristics and clinical profiles of the 13 patients are presented in Table 1. Table 2 summarizes the posterior segment complications found in this group of patients. The following case reports are representative of the clinical 1273
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Table 2. Posterior Segment Findings in Thirteen Patients with Inflammatory Bowel Disease Findings Serous retinal detachment with Choroidal infiltrates RPE leak Papillitis Choroidal infiltrates without serous retinal detachment Retrobulbar neuritis Choroidal folds
No. of Patients
Case No.
8 3 4 1
1, 5, 6, 8, 10-13 1,10,11 5,6, 12, 13 8
3 1 1
4, 7, 9 2 9
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roidal infiltrates were found temporal to the macula (Figs 4, 5). Figures 6A, B, and C demonstrate the fluorescein angiographic findings. Prednisone (100 mg daily) was started. The patient had a dramatic response to systemic steroid therapy showing complete resolution of the bilateral serous detachments within 24 hours. The ocular signs and symptoms recurred several time as steroids were tapered. The patient finally underwent bowel resection. There have been no recurrences of eye disease in a 14year follow-up.
CHOROIDAL INFILTRATES
course of the most common posterior segment manifestations seen in our patients: choroidal infiltrates with or without overlying serous retinal detachment and choroidal leaks with overlying serous retinal detachment.
CASE REPORTS CHOROIDAL INFILTRATES WITH OVERLYING SEROUS RETINAL DETACHMENT Case 1. A 28-year-old woman complained of decreased vision in her left eye and headache for I week. Four years previously, the patient was diagnosed with Crohn's disease. She was maintained on sulfasalazine (Azulfidine), and a single recurrence of Crohn's disease occurred 6 months before her current symptoms. Her visual acuity was 20/15 in the right eye and hand motions in the left. The left eye had an afferent pupillary defect. The anterior chambers were quiet. Bilateral, muItifocal, yellowish choroidal lesions were scattered in the posterior poles within areas of overlying serous retinal detachments. In the left eye, localized areas of serous retinal detachments were seen in the macula, temporal arcades (Fig I), and nasal to the disc (Fig 2). Fluorescein angiographic findings of the left eye are presented in Figures 3A, B, and C. The right eye was similar but had a larger area of shallow confluent serous retinal detachment. Oral prednisone (80 mg daily) was begun. One week later, visual acuity in the left eye improved to 20/40 with partial resolution of the serous retinal detachment. Systemic steroids were discontinued after being tapered over 3 weeks. Visual acuity returned to 20/20, and the serous retinal detachments and choroidal infiltrates resolved with minimal retinal pigment epithelial disturbance. Case 10. A 40-year-old man presented with a 4-week history of blurred vision, frequent diarrheal stools, left lower quadrant cramps, and bilateral frontal and retro-orbital headache. Six years before, the patient presented with generalized erythematous, raised pruritic eruption, a history of bloody stools, and many small, whitish vesicles on the oral mucosa. Results of sigmoidoscopy showed ulcerative colitis. His atypical dermatitis herpetiformis, colitis, and aphthous stomatitis responded to a brief regiment of systemic corticosteroids. Visual acuity was 20/40 in the right eye and 20/50 in the left. The anterior segments were quiet. Multifocal, yellowish choroidal lesions with indistinct borders measuring approximately '16 disc diameter in size were scattered throughout the posterior pole. Bilateral localized serous retinal detachments overlying the cho-
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Case 7. A 20-year-old man with active Crohn's disease had decreased vision in both eyes for 2 months' duration. Visual acuity was 20170 in the right eye and 20/25 in the left. The anterior chambers had 2+ cells and flare and there was moderate bilateral vitreitis. Multifocal, yellowish choroidal lesions measuring Vs disc diameter in size were widely distributed throughout the posterior segments, and in some areas they were confluent (Figs 7A, B). The change in the clinical appearance of the choroidallesions was documented over several weeks. The early, active lesions were yellowish with hazy, soft, indistinct borders. The active lesions blocked fluorescein in the choroidal phase and stained in the late phases (Figs 8A, B). As the choroidal lesion aged, sharp borders developed, which were associated with retinal pigment epithelial disturbance and choroidal scarring. Prednisone (100 mg daily) was begun. Within 3 weeks, visual acuity improved to 20/30 in the right eye and 20/20 in the left. Tapering of steroids resulted in a recurrence of choroiditis associated with a flare ofCrohn's disease. The terminal ileum and ascending colon were resected. No new choroidal lesions developed after the surgery, but the patient continued to have recurrent iritis and mild recurrences of his bowel disease. Finally an active focus of Crohn's disease in the rectal region was treated successfully and the bowel disease and uveitis remitted at the same time. This patient has not had a recurrence in 5 years of follow-up. Case 4. A 27-year-old woman presented with a to-day history of blurred vision, headache, fever, generalized myalgia, arthralgia, and diarrhea. A painful eruption consistent with erythema nodosum was noted on the left pretibial area. Subtotal colectomy confirmed the diagnosis of ulcerative colitis 1 year previously. Visual acuity was 20/25 in both eyes. The conjunctiva and episclera were injected bilaterally. The right anterior chamber had 1+ cell and flare and the left anterior chamber had 3+ cells and 1+ flare. Multifocal, yellowish-white choroidal lesions were present bilaterally (Fig 9). In this particular case, the choroidal infiltrates in the midperiphery had a more homogeneous and slightly thickened appearance. Choroidal hemorrhages were present along the borders of the lesions (Fig 10). The fluorescein angiographic findings are demonstrated in Figures 11 A and B. Topical steroids and cycloplegics were instituted. Systemic steroids were withheld pending laboratory evaluation. Two weeks later, the anterior segment inflammation was almost resolved. Choroidal lesions of various ages and in various stages of activity were noted in the posterior segments of both eyes as described in the previous case report (case 7). Active choroidal lesions had indistinct borders and demonstrated blockage of fluorescein in the early phases and older inactive lesions had sharp borders and less blockage of fluorescein in the arteriovenous phase. Focal sheathing of blood vessels was noted in both eyes and new choroidallesions developed in the left macula. Over the next 4 weeks, new choroidal infiltrates continued to appear as others became inactive, and further nodular eruptions were discovered on her legs. At this point, proctoscopy demonstrated pouchitis and a
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Fig 1. Top left, case I. Localized serous retinal detachments in the macula (between large arrows) and temporal arcades (small arrows), of the left eye. Fig 2. Top right, case I. Localized serous retinal detachment (between arrows) nasal to the left disc. Fig 3. Case I. Early, middle, and late phases of the angiogram document multifocal choroidal lesions, which block fluorescein in the early phase (center l eft , A), develop confluence of staining (center right, B), and accumulate fluorescein within the area of serous retinal detachment in the late frames (bottom left , C). Fig 4. Bottom right, case 10. Serous retinal detachment was present in the macula (between arrows) of the right eye.
perianal abscess. Prednisone, 15 mg daily, was initiated. Two weeks later, visual acuity returned to 20/20 in both eyes and no new choroidal lesions were noted. After remission, multifocal atrophic choroidal scars were evident in the posterior pole. The patient has not had a recurrence in 2 years of follow-up.
SEROUS RETINAL DETACHMENT AND CHOROIDAL LEAKS
Case 12. A 49-year-old man had active bowel disease when he presented with a 2-week history of blurred vision in his left
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Fig 5. Top left. case 10. Localized serous retinal detachment (between arrows) overlying choroidal infiltrates temporal to the right macula. Fig 6. Case 10. Early, middle, and late phases of the angiogram demonstrate blocking of fluorescein by the choroidal infiltrates in the early phase (top righI, A), staining of the lesions (cenler left, B), and accumulation of fluorescein within the area of overlying serous retinal detachment (center right, C). Fig 7. Case 7. Multifocal choroidal lesions of various ages scattered in the posterior pole. The early, acute lesions have indistinct borders (large arrows). The older, inactive lesions have sharp borders (small arrows) and are associated with retinal pigment epithelium disturbance and scarring (boltom left, A). In some areas the choroidal lesions were confluent (between arrows) (boltom right, B).
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Fig 8. Case 7. The active lesions blocked fluorescein in the early phases (left, A) and stained in the late phases (right, B).
eye. A diagnosis of ulcerative colitis was made 2 years previously from results of a biopsy specimen. He was maintained on azulfidine and prednisone. The dosage of prednisone had just been decreased from 30 mg to 20 mg when the visual symptoms developed. Visual acuity was 20/20 in the right eye and 20/30 in the left. Both maculae had marked pigmentary disturbance. There were three focal areas of paramacular serous retinal detachment in the left eye (Fig 12). Results of fluorescein angiography showed multifocalleaks from the choroid within the areas of serous retinal detachment (Figs 13A, B). The patient had focal photocoagulation treatment to the areas of leakage. The serous retinal detachment nasal to the fovea persisted and new areas of focal serous retinal detachment were identified 5 months later, and the patient received additional photocoagulation. During this period of observation, the ulcerative colitis remained active with active mucosal fissures in the rectum. After 8 months, the bowel disease became quiescent with complete resolution of the serous retinal detachment. There have been no recurrences.
DISCUSSION This study describes 13 patients with posterior segment manifestations associated with inflammatory bowel disease. A spectrum of findings resulting from ocular inflammation involving the choroid and the optic nerve are reported. Choroidal infiltrates were the most common findings. Six patients (cases I, 4, 7, 9, 10, and 11). had multifocal, yellow-white choroidal infiltrates. The infiltrates were bilateral in five of six patients. The lesions appeared most often in the posterior pole. They measured less than 112 disc diameter and, in some patients, they were confluent. Acute, active lesions had soft, indistinct borders. Systemic corticosteroid therapy rapidly induced remission in the choroidal lesions resulting in atrophic or hyperpigmented scars. Untreated lesions healed spontaneously (case 4) but new lesions continued to form until systemic corticosteroids were instituted. The nature of these infiltrates is uncertain, but histopathologic studies of an eye enucleated with panuveitis from a patient with Crohn's disease demonstrated choroidal granulomas. 7
However, choroidal granulomas are an unlikely explanation for choroidal infiltrates occurring in patients with ulcerative colitis because granulomas are not part of the intestinal disorder. In heavily involved areas or areas of confluent choroidal infiltrates, serous retinal detachments were commonly identified. Results of fluorescein angiography showed the acute or early choroidal lesions blocked fluorescein in the early phases of the angiogram and developed late staining. A similar pattern has been described for other disorders. Acute multi focal placoid pigment epitheliopathy has subretinal infiltrates with a similar angiographic appearance. Lesions similar to acute multifocal placoid pigment epitheliopathy have been reported in regional enteritis. II These lesions are grayish, involving the RPE, and heal with diffuse pigmentary disturbance. Further, serous retinal detachment seen in three of our patients with choroidal infiltrates is an uncommon occurrence in acute multifocal placoid pigment epitheliopathy.12 Multiple evanescent white dot syndrome has white infiltrates with a different angiographic appearance that do not scar.12 Choroidal lesions also occur in syphilis and tuberculosis, but serology or skin testing did not support these diagnoses in our patients. Sarcoidosis, sympathetic ophthalmia, and Harada's disease can cause focal choroidal infiltrates, but our patients did not have clinical findings suggestive of these diseases. Posterior scleritis has been reported in patients with inflammatory bowel disease,5,13 and choroidal infiltrates can be seen overlying a choroidal mass in posterior scleritis. 12- 14 Ultrasonography was not performed in our patients, and an associated posterior scleritis can not be excluded in cases 1,4, 7, 9, 10, and 11. Bilateral choroidal folds were present in one patient. These folds were demonstrated on two successive fluorescein angiograms taken several weeks apart and resolved spontaneously. There was no hypotony, papilledema, or choroidal mass when the choroidal folds were observed. A similar angiographic pattern has been reported in patients with benign lymphoid hyperplasia and lymphocytic 1277
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Fig 9. Top left, case 4. Early (active) multifocal choroidal lesions in left macula. Fig 10. Top right, case 4. Choroidal infiltrates in the midperiphery have a more homogeneous and thickened appearance, associated with choroidal hemorrhages. Fig 11. Center, case 4. Active choroidal lesions block fluorescein in the early phase of the angiogram (left, A) and stain in the late phases (right, B). Fig 12. Bottom, case 12. Focal serous retinal detachments (small arrows) in the paramacular region and temporal to the left disc (large arrows).
infiltration ofthe choroid. 15 The mechanism for choroidal folds in our patient is uncertain. In addition to choroidal folds, this patient had multifocal choroidal infiltrates in
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one eye. A more diffuse cellular infiltration in addition to the focal choroidal infiltrates may have caused thickening of the choroid resulting in choroidal folds.
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Fig 13. Case 12. Fluorescein angiography shows focal areas of hyperfluorescence within the paramacular and peripapillary areas in the early arteriovenous phase (left, A). These areas increase in intensity and late staining develops at the temporal edge of the disc within the area of serous retinal detachment and three discrete choroidal leaks are seen within the serous retinal detachment in the paramacular area (right, 8).
Papillitis was present in two patients and has been previously reported in association with inflammatory bowel disease by Macoul9 and Heuer et al. 8 Their patients were young men with Crohn's disease who had severe bilateral optic nerve involvement resulting in neuroretinitis9 and ischemic optic nerve damage. 8 Our patients (cases 2 and 8) also had Crohn's disease but were young women with unilateral optic nerve involvement and good vision. Retrobulbar neuritis in case 2 was mild and was characterized by a relative afferent pupillary defect, abnormal color testing, and a normal field. Case 8 had marked elevation of the left optic nerve with associated relative afferent pupillary defect and serous retinal detachment. Both patients had resolution of their optic nerve inflammation without sequelae. Permanent arcuate field defects have occurred in previously reported cases, despite treatment with systemic corticosteroids. 8 Cerebrospinal fluid lymphocytosis present in case 2 suggests that a similar type of infiltration may be occurring in the optic nerves of these patients. Four of our patients had serous retinal detachments and choroidal leaks (cases 5, 6, 12, and 13). These complications have been associated with inflammatory bowel disease. 5,6 These serous retinal detachments with choroidal leaks have the same characteristics as idiopathic central serous choroidopathy originally described by GasS. 16 Gass was careful to differentiate idiopathic central serous choroidopathy from juvenile disciform degeneration, which is an inflammatory disorder with a positive test for histoplasmosis.1 6 Two of our patients had choroidal leaks with an overlying serous retinal detachment that resolved with systemic corticosteroids alone, suggesting that central serous choroidopathy in patients with inflammatory bowel disease also may be inflammatory in nature. Laser therapy has previously been used to treat central serous choroidopathy in inflammatory bowel disease6 and was effective in treating central serous choroidopathy in two of our patients (cases 6 and 12). Systemic corticosteroid therapy should be tried before laser photocoagulation is undertaken in these patients.
Understanding ocular manifestations of inflammatory bowel disease is difficult since the pathogenesis of the intestinal disorder is unclear. Infectious causes are poorly supported by cultures, electron microscopy, transmissibility, or response to antibiotics. Although Mycobacterium paratuberculosis has been isolated in cultures of biopsy specimens obtained from patients with inflammatory bowel disease,17 it is an inconsistent finding and is often present in normal populations. Genetic factors may play a role in the pathogenesis of inflammatory bowel disease. There is an increased incidence of disease in Ashkenazi Jews and first-degree relatives. Further, patients with inflammatory bowel disease with spondylitis have a higher incidence of the HLA-B27 antigen. Immune pathogenesis is suggested by histologic and humoral alterations. Increased populations of intestinal lymphocytes occur in inflammatory bowel disease. Intestinal plasma cell numbers increase with active disease. Tcell subtypes are normal, but a loss of normal T -suppressor response occurs during active disease. I Circulating anticolonic epithelial antibodies are seen, which result in Tcell-mediated cytolysis. 18 The incidence of anticolonic epithelial antibodies also is increased in family members. 19 The extraintestinal manifestations of inflammatory bowel disease are well recognized and include liver, skin, eye, and joint disease. Migratory arthralgias20 and ocular and skin manifestations typically occur when intestinal disease is active. I Activation of abnormal intestinal immunity in inflammatory bowel disease may result in circulating antibodies or antigen-antibody complexes21 that can mediate extraintestinal complications. Inflammatory bowel disease was active in 50% of our patients when posterior segment abnormalities were observed. Resection of the actively inflamed bowel reduces and often leads to resolution of extraintestinal manifestations in the eyes, skin, and joints. 2 In four of our patients (cases 7, 10, 12, and 13) bowel resection was temporally related to the resolution of their eye disease. The incidence of arthritis, pericholangitis, and skin disorders are signif1279
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icantly reduced in patients with inflammatory bowel disease patients who are taking corticosteroids. 22 Systemic corticosteroid treatment also appears to have an effect on ocular posterior segment disease. In case 12, systemic corticosteroid had been reduced immediately before the onset of posterior segment disease. Nine of 13 patients' posterior segment disorders responded rapidly to systemic corticosteroid treatment. Case 4 had coincident resolution of her eye disease when oral prednisone was taken for pouchitis and perianal abscess. Posterior segment manifestations of inflammatory bowel disease have not been commonly recognized. 3- 10 In our series, it also appears that the incidence of posterior segment manifestations is low, being less than 1% of patients with inflammatory bowel disease at our institution. This low incidence also may be attributed to the frequent use of corticosteroids in inflammatory bowel disease22 and the rapid resolution of posterior segment manifestations with systemic corticosteroid therapy. Coincidental ocular inflammation may have resulted in focal choroidal leaks and optic neuritis. In our patients with focal choroidal leaks, a high incidence of concurrent active bowel disease and improvement of ocular disease associated with bowel resection in two patients suggests that the disorders may be related. It is hoped that this report will lead to an increased recognition of posterior segment complications associated with inflammatory bowel disease; with a heightened awareness, ophthalmologists will be better guided toward diagnosis and management of this group of eye findings.
REFERENCES 1. Strober W, James SP. The immunologic basis of inflammatory bowel disease. J Clin Immunol1986; 6:415-32. 2. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's di~ease and ulcerative colitis: a study of 700 patients. Medicine 1976; 55:401-12. 3. Hopkins OJ, Horan E, Burton IL, et aI. Ocular disorders in a series of 332 patients with Crohn 's disease. Br J Ophthalmol1974; 58:732-7. 4. Billson FA, De Dombal FT, Watkins G, Goligher JC. Ocular complications of ulcerative colitis. Gut 1967; 8:1 02-6.
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5. Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn's disease. Ophthalmology 1984; 91:163-73. 6. Kaneko E, Nawano N, Honda N, et al. Ulcerative colitis complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment. Dig Dis Sci 1985; 30:896-900. 7. Salmon JF, Wright JP, Bowen RM, Murray AD. Granulomatous uveitis in Crohn's disease. A clinicopathologic case report Arch Ophthalmol 1989; 107:718-9. 8. Heuer OK, Gager WE, Reeser FH. Ischemic optic neuropathy associated with Crohn's disease. J Clin Neuro-Ophthalmol 1982; 2:1 7581. 9. Macoul KL. Ocular changes in granulomatous ileocolitis. Arch Ophthalmol1970; 84:95-7. 10. Zaidman GW, Coles RS. Peripheral uveitis and ulcerative colitis. Ann Ophthalmol 1981; 13:73-6. 11. Gass JDM. Acute posterior multifocal placoid pigment epitheliopathy: a long-term follow-up study. In: Fine SL, Owens SL, eds. Management of Retinal Vascular and Macular Disorders. Baltimore: 1983 Williams & Wilkins 1983; 176. 12. Gass JDM. Stereoscopic Atlas of Macular Diseases. Diagnosis and Treatment, 3rd ed. St. Louis: CV Mosby Co, 1987. 13. Benson WE. Posterior scleritis. Surv OphthalmoI1988; 32:297-316. 14. Benson WE, Shields JA, Tasman W, Crandall AS. Posterior scleritis: a cause of diagnostic confusion . Arch Ophthalmol1979; 97:1482-6. 15. Desroches G, Abrams GW, Gass JD. Reactive lymphoid hyperplasia of the uvea: a case with ultrasonographic and computed tomographic studies. Arch Ophthalmol1983; 101 :725-8. 16. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol 1967; 63:587-615. 17. Hodgson HJF, Jewel DP. Immunology of inflammatory bowel disease. Baillieres Clin Gastroenterol1987; 1531-45. : 18_ Auer 10, Grosch L. HardOrfer C, ROder A. Ulcerative colitis specific cytotoxic IgG autoantibodies against colonic epithelial cancer cells. Gut 1988; 29:1639-47. 19. Fiocchi C, Roche JK, Michener WM. High prevalence of antibodies to intestinal epithelial antigens in patients with inflammatory bowel disease and their relatives. Ann Intem Med 1989; 110:786-94. 20. Donaldson RM. Crohn's Disease. In: Sieisenger MH, Fordtran JS, eds. Gastrointestinal Disease, 4th ed. Philadelphia: WB Saunders, 1989; vol. 1, chap. 71. 21 . Hodgson HJF, Potter BJ, Jewell DP. Immune complexes in ulcerative colitis and Crohn's disease. Clin Exper ImmunoI1977; 29:187-96. 22. Kemler BJ, Alpert E. Inflammatory bowel disease: study of cell mediated cytotoxicity for isolated human colonic epithelial cells. Gut 1980; 21 ;353-9.
