Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2009; 13(Suppl 1): 11-13 Ophthalmological aspects of IBD

C. MANGANELLI, S. TURCO, E. BALESTRAZZI

Department of , Catholic University of the Sacred Heart, Rome (Italy)

Abstract. – Ocular manifestations occur in Immunological mechanisms are linked to au - 4-12% of patients with IBD. and iritis are toimmunity. Many observations confirm the more frequently associated with ulcerative coli - presence of autoantibodies in patients with IBD tis while is more common in Crohnʼs and the occurrence of immunologic interactions disease. Some ocular manifestations in IBD can be secondary to treatment and/or effects of the between bacterial endotoxins and host immune intestinal disease itself. system. The efficacy of immunomodulatory ther - The specific management of ocular manifesta - apies confirms this autoimmune hypothesis. tions in IBD requires the use of topical steroids Ocular manifestations occur in 4-12% of pa - and FANS, cycloplegics, systemic steroids or tients with IBD (Table I). immunosuppressive drugs. Uveitis and iritis are more frequently associ - When conventional therapies fail to control the ocular manifestations in IBD, the new biolog - ated with ulcerative colitis while episcleritis is ic drugs can be considered as good alternative more common in Crohn’s disease. Other de - treatments. Early diagnosis and effective treat - scribed eye complications are: , ment may avoid the onset of severe and some - , , retinal vasculitis, papillitis times persisting complications. In some cases, a and orbital myositis. These manifestations are surgical approach is required to treat eye com - usually associated with active bowel disease, plications, i.e. , and to improve the pa - but asymptomatic uveitis can occur more fre - tientʼs quality of life. quently in patients with Crohn’s colitis (18%) Key Words: rather than in those with small bowel lesions. Ocular manifestations, Uveitis, Episcleritis, IBD. Since asymptomatic uveitis has been reported in IBD children with a frequency of 6% slit-lamp routine examination is recommended in this group of patients. Introduction Some ocular manifestations in IBD can be sec - ondary to treatment and/or effects of the intesti - nal disease itself (i.e. steroid cataract or emer - Systemic and extraintestinal manifestations alopia and xerophthalmia due to mal - (EIM) are common in patients with Inflammato - absorption). ry Bowel Disease (IBD). These manifestations can involve almost any organ, however the eyes with skin, joints and biliary tract are most fre - Table I. Ocular manifestations of IBD. quently affected. The occurrence of one EIM predisposes to Episcleritis, scleritis other extracolonic involvements (ocular and/or Uveitis joint manifestations have been described in 50 to Neurophthalmologic complications 90% of patients affected by active IBD and pyo - (papillitis, retrobulbar neuritis, neuroretinitis) derma gangrenosum). Retinal vascular disease Pathophysiological mechanisms of EIMs in Corneal infiltrates IBD are not clearly understood, but genetic and Orbital pseudotumour immunologic factors play an important role. Orbital myositis Genetic polymorphisms not only determine Recurrent nonspecific follicular conjunctivitis the susceptibility of developing Crohn’s disease Nonspecific or ulcerative colitis but also influence the pheno - Lid swelling type of the disease, including EIMs.

Corresponding Author : C. Manganelli, MD; e-mail: c.manganelli@rm. unicatt.it 11 C. Manganelli, S. Turco, E. Balestrazzi

Clinical Pictures the main diagnostic investigation. Signs of occlu - sive arteritis can predominate in patients affected Episcleritis (Figure 1) is an inflammation of by periarteritis with cotton wool spots, ischemia the episclera presenting with hyperemia of the and neovascularization. and episclera. It is generally painless Retinal vasculitis may lead to cystoid macular and can occur in nodular or diffuse forms. Scleri - edema (Figure 2) and/or edema and tis is rare, bilateral in 1/3 of cases. Acute pain, optic atrophy. deep and periorbital is characteristic. An impor - Papillitis (Figure 3) is inflammation of the op - tant visual loss can be present in 30% of cases tic nerve head based on immunoallergic phenom - and the eye is deeply red. Four different forms ena. The mechanism is related to a vasculitis and are described: anterior nodular scleritis, anterior perivasculitis process involving retinal and neu - diffuse scleritis, necrotizing scleritis without in - roretinal vessels. It can be transient and re - flammatory signs (scleromalacia perforans), pos - versible or it may proceed toward optic atrophy. terior scleritis. It is generally associated with sys - Fluorescein angiography and perimetry are em - temic diseases mostly RA and Wegener’s dis - ployed for the diagnosis. ease, but an association with IBD is reported. Corneal infiltrates are clumps of leukocytes: The diagnosis is clinical and additional informa - they can occur in association with active corneal tion can be derived by fluorescein angiography infections or under sterile conditions for an im - or UBM echography. munologic response. The overlying can Anterior uveitis in IBD is classified as an en - be normal or show an epithelial defect with a dogenous non infectious inflammation of the central or peripheral ulcer. anterior . Pain, , tearing and blurred vision are characteristic, but sometimes it can be asymptomatic. The clinical picture is Treatment characterized by hyperemia, perikeratic injec - tion, exudates in the anterior chamber, keratic precipitates and involvement. The diagnosis Some extraintestinal manifestations may re - is clinical. spond to underlying IBD treatment. Retinal vasculitis can involve arterial or ve - Episcleritis is generally influenced by the ac - nous vessels with peri or endovasculitis. Pe - tivity of the intestinal disease while uveitis tends riphlebitis is the most frequent manifestation. to have an independent course. Vascular walls show diffuse or focal sheathing The specific management of ocular manifesta - and infiltration. Vasculitis can induce vascular tions in IBD requires the use of topical steroids occlusion with following neovascularization and and FANS, cycloplegics, systemic steroids or im - retinal hemorrhages. Fluorescein angiography is munosuppressive drugs such as cyclosporine A, methotrexate, tacrolimus, azathioprine for the au - toimmune pathogenetic mechanism. When conventional therapies fail to control the ocular manifestations in IBD, the new biolog - ic drugs can be considered as good alternative treatments. Tumor Necrosis Factor- α blockade

Figure 1. Figure 2. Episcleritis. Severe (OCT).

12 Ophthalmological aspects of IBD

References

IMRIE FR, D ICK AD 1) . Biologic in the treatment of uveitis. Curr Opin Ophthalmol 2007; 18: 481-486. AYLOR SRJ, M CCLUSKEY P, L IGHTMAN S. 2) T The ocular manifestations of inflammatory bowel disease. Curr Opin Ophthalmol 2006; 17: 538-555. DUKER JS, B ROWN GC, B ROOKS L 3) . Retinal vasculitis in Crohnʼs disease. Am J Ophthalmol 1987; 103: 664-668. HUDSON M, C HITOLIE A, H UTTON RA, S MITH MS, 4) POUNDER RE, W AKEFIELD AJ. Thrombotic vascular risk factors in inflammatory bowel disease. Gut 1996; 38: 733-777. SALMON JF, W RIGHT JP, M URRAY AD 5. . Ocular inflam - mation in Crohnʼs disease. Ophthalmology 1991; 98: 480-484. GEERARDS AJ, B EEKHUIS WH, R EMEYER L, R IJNEVELD AJ, 6) VREUGDENHIL W . Crohnʼs colitis and the cornea. Figure 3. Papillitis (fluorescein angiography). Cornea 1997; 16: 227-231. VERBRAAK FD, S CHREINEMACHERS MC, T ILLER A, VAN DE- 7) VENTER SJ, DE SMET MD . Prevalence of subclinical an - terior uveitis in adult patients with inflammatory bowel disease. Br J Ophthalmol 2001; 85: 219-221. ERNST BB, L OWDER CY, M EISLER DM, G UTMAN FA has been effective after failure of conventional 8) . immunosuppression since TNF- α is a proinflam - Posterior segment manifestations of inflammatory matory cytokine which has been implicated as an bowel disease. Ophthalmology 1991; 98: 1272- 1280. important mediator in autoimmune ocular in - WEINSTEIN JM, K OCH K, L ANE S flammatory disease pathogenesis. This treatment 9) . Orbital pseudotu - mor in Crohnʼs colitis. Ann Ophthalmol 1984; 16: is empirical and supported by small case series in 275-278. the literature due to the relatively low prevalence HEUER DK, G AGER WE, R EESER FH 10) . Ischemic optic of ocular manifestations in IBD. neuropathy associated with Crohnʼs disease. J Infliximab , a chimeric monoclonal antibody Clin Neuroophthalmol 1982; 2: 175-181. α, α SAMSON CM, W AHEED N, B ALTATZIS S, F OSTER CS to TNF- and etanercept , an anti-TNF- re - 11) . combinant fusion protein, have been used in Methotrexate therapy for chronic non-infectious some cases of ocular inflammation in IBD. Ret - uveitis: analysis of a case series of 160 patients. rospective studies show that infliximab seems Ophthalmology 2001; 108: 1134-1139. NUSSENBLATT RB, P ALESTINE AG, C HAN CC more effective in the treatment of uveitis. The 12) . Cy - need for retreatment because of relapses and closporine therapy for uveitis: long-term follow- high cost represent limiting factor for the use of up. J Ocul Pharmacol 1985; 1: 369-382. KILMARTIN DJ, F ORRESTER JV, D ICK AD biologics. 13) . Tacrolimus In conclusion, a multidisciplinary approach (FK506) in failed cyclosporine A therapy in en - is recommended in the management of patients dogenous posterior uveitis. Ocul Immunol In - flamm 1998; 6: 101-109. with IBD, including ocular manifestations. Ear - HALE S, L IGHTMAN S. ly diagnosis and effective treatment may avoid 14) Anti-TNF therapies in the management of acute and chronic uveitis. Cy - the onset of severe and sometimes persisting tokine 2006; 33: 231-237. complications. In some cases, a surgical ap - HOFLEY P, R OARTY J, M CGINNITY G, G RIFFITHS AM, M AR - 15) CON M, K RAFT S, S HERMAN P. proach is required to treat eye complications, Asymptomatic uveitis i.e. cataract, and to improve the patient’s quali - in children with chronic inflammatory diseases. J ty of life. Pediatr Gastroenterol Nutr 1993; 17: 397-400.

13