Ophthalmic manifestations in patients with inflammatory bowel disease: A review

Table 1 Studies evaluating ocular manifestations in inflammatory bowel disease patients

Ref.	Country	Study design	Ocular exam sample	Ocular manifestationfrequency	Comment
Karmiris et al[56] (2016)	Greece	Prospective cohort	1860 (1001 CD; 859 UC)	55 (3%)	Ocular EIMs represented the third most frequent group of EIM in the study
				(45 CD; 10 UC): 31 Anterior uveitis (25 CD; 6 UC); 16 Episcleritis (16 CD); 7 Posterior uveitis (3 DC; 4 UC); 1 Central serous retinopathy (CD)	All patients with episcleritis suffered from CD. There were patients with anterior and posterior uveitis
Manser et al[57] (2016)	Switzerland		140 UC patients with EIM or complications	22 (15.7%) Uveitis	Investigated prevalence of uveitis in patients with UC
Bandyopadhyay et al[27] (2015)	India		120 (62 CD; 58 UC)	16 (13%)(8 CD; 8 UC): 7 Uveitis (7 CD); 9 Episcleritis (1 CD; 8 UC)	Authors describe two cases of scleritis (2 CD) and one of endophthalmitis (CD) that were not accounted as ocular manifestations. Authors consider a selection bias, as most participants had severe intestinal disease
Isene et al[58] (2015)	Europe (Norway, Denmark, Netherlands, Spain, Italy, Greece, and Israel)	Prospective cohort	1145 (364 CD; 781 UC)	12 (1.0%)10 (0.9%) Anterior uveitis; 2 (0.2%) Episcleritis	Authors concluded that familial IBD does not predict increased risk of immune-mediated EIM, as smoking does not seem to influence the risk
Zippi et al[28] (2014)	Italy	Retrospective	811 (216 CD; 595 UC)	26 Uveitis (3.2%)(16 CD; 10 UC)	It is not informed if other ocular manifestations have been investigated in addition to uveitis.
Cloché et al[59] (2013)	France		74 IBD (no underlying disease specification)	1 (1.4%): Scleritis	A large number of patients were receiving biological agents, approximately 50%, that may treat IBD and prevent ocular inflammation. Authors do not define the underlying IBD of the scleritis patient
Vavricka et al[22] (2011)	Switzerland	Prospective Cohort	950 (580 CD; 370 UC)	50 (5.3%)(36 CD; 14 UC): 50 Uveitis	Only uveitis was considered ocular EIM, and it was associated to active CD, but no relation was found to UC activity
Cury et al[60] (2010)	Brazil		88 (48 CD; 40 UC)	7 (6.25%)(no underlying disease specification): 1 Conjunctivitis; 3 Blepharitis; 1 Episcleritis; 2 Uveitis; 2 Cataracts	The study used a control group of 24. Considered also unspecific ocular abnormalities, as cataract and blepharitis
Felekis et al[61] (2009)	Greece	Prospective cohort	60 (23 CD; 37 UC)	26 (43%)(12 CD; 14 UC): 13 Dry eye; 8 Glucocorticoid-induced cataract; 3 Iridociclitis; 3 Retinal pigment epithelium disturbances; 2 Episcleritis; 2 Serous retinal detachment; 1 Conjunctivitis; 1 Choroiditis; 1 Vasculitis; 1 Optic neuritis	The study used a control group of 276. Authors conclude that ocular manifestations occur in UC patients as frequently as in CD patients; however, the results of the statistical analysis are not mentioned for any of the study variables
Lanna et al[25] (2008)	Brazil		96 (59 CD; 37 UC)	6 (6.2%)(4 CD; 2 UC): 4 Uveitis (2 bilateral; 2 CD; 2 UC); 1 Scleritis (CD); 1 Episcleritis (CD)	It was not possible to analyze the association between the HLA-B27 and ocular abnormalities because only 3 of the 6 patients had been tested for HLA-B27; all of them were negative for this antigen
Yilmaz et al[35] (2007)	Turkey	Prospective cohort	116 (20 CD; 96 UC)	28 (24.13%)(12 CD; 22 UC): 10 Conjunctivitis; 8 Blepharitis; 6 Uveitis; 6 Cataracts; 4 Episcleritis	Study considered unspecific ocular abnormalities, as cataract and blepharitis, which are very frequent in the general population
Mendoza et al[29] (2005)	Spain	Prospective cohort	566 (295 CD; 271 UC)	13 (2.3%)(6 CD; 7 UC): 8 Uveitis (2 CD; 6 UC); 5 Episcleritis (4 CD; 1 UC)	In 2 patients the ophthalmologic clinical presentation preceded the diagnosis of IBD, but its frequency is probably undervalued considering the high prevalence of asymptomatic uveitis
Ricart et al[47] (2004)	United States		243 IBD [47 familial IBD (25 CD; 22 UC); 196 sporadic IBD (114 CD; 82 UC)]	Familial IBD: 3 (2 CD; 1 UC)Sporadic IBD: 10 (7 CD; 3 UC)Authors don't specify which ocular EIM was found	Significant association between EIM and disease status (familial vs sporadic) was not detected. This suggests that susceptibility genes for the development of IBD and the susceptibility genes for the development of EIM are different
Lakatos et al[2] (2003)	Hungary	Prospective cohort	873 (254 CD; 619 UC)	28 (3.2%)(8 CD; 20 UC): 13 Conjunctivitis (4 CD; 9 UC), 10 Anterior uveitis (4 CD; 6 UC); 5 Scleritis (1 CD; 4 UC); 1 Orbital pseudotumor (female UC patient)	The prevalence was more frequent in women in both UC and CD. In UC more than half of the patients with ocular complication had pancolitis
Christodoulou et al[62] (2002)	Greece	Retrospective	248 (37 CD; 215 UC)	4 (1.61%)(1 CD; 3 UC): 4 Iridocyclitis	Evaluated only iridocyclitis as ocular EIM

CD: Crohn’s disease; EIM: Extraintestinal manifestation; IBD: Inflammatory bowel disease; UC: Ulcerative colitis.

Table 2 Uveitis classification

SUN classification	Primary site of inflammation	Manifestation
Anterior uveitis	Anterior chamber	Iritis, iridocyclitis, anterior cyclitis
Intermediate uveitis	Vitreous	Pars planitis, posterior cyclitis, hyalitis
Posterior uveitis	Retina or choroid	Focal, multifocal or diffuse choroiditis, chorioretinitis, retinochoroiditis, retinitis, neuroretinitis
Panuveitis	Anterior chamber, vitreous, and retina or choroid

Adapted from Standardization of Uveitis Nomenclature Working Group[70]. SUN: Standardization of Uveitis Nomenclature Working Group.

Table 3 Case reports and case series of other ocular manifestations associated with inflammatory bowel disease

Ref.	Country	Ocular impairment	IBD
Hwang et al[89] (2001)	Canada	Dacryoadenitis	CD
Mochizuki et al[90] (2010)	Japan		UC
Boukouvala et al[91] (2012)	United Kingdom		CD
Jakobiec et al[92] (2014)	United States		2 CD
Ruiz Serrato et al[15] (2013)	Spain	Palpebral ptosis	CD
Diaz-Valle et al[93] (2004)	Spain	Lid margin ulcers	CD
Leibovitch et al[94] (2005)	Australia	Pyodermatitis-pyostomatitis vegetans of eyelids	UC
Garrity et al[95] (2004)	United States	Orbital myositis	2 CD
Verma et al[96] (2013)	Canada		CD
Foroozan et al[97] (2003)	United States	Ocular miasthenia graves	UC
Pham et al[31] (2011)	United States	Peripheral ulcerative keratitis	3 CD
Roszkowska et al[98] (2013)	Italy	Salzmann nodular corneal degeneration	CD
Zullow et al[99] (2017)	United States	Central serous chorioretinopathy	UC
Geyshis et al[100] (2013)	Israel		UC
Assadsangabi et al[101] (2010)	United Kingdom		CD
Ugarte et al[102] (2002)	United Kingdom	Serpiginous chorioretinopathy	CD
Casalino et al[103] (2014)	Italy	Choroidal neovascularization	CD
Thomas et al[104] (2014)	United States		CD
Unal et al[105] (2008)	Turkey		CD
Saatci et al[106] (2002)	Turkey	Retinal vasculitis	CD
Larsson et al[107] (2000)	Sweden	Retinal vein occlusion	1 CD, 1 UC
Buchman et al[108] (2006)	United States		UC
Unal et al[105] (2008)	Turkey		CD
Yamane et al[109] (2007)	Brazil		CD
Vayalambrone et al[110] (2011)	United Kingdom		UC
Falavarjani et al[111] (2012)	Iran	Retinal artery occlusion	CD
Abdul-Rahman et al[112] (2010)	New Zealand		CD
Saatci et al[106] (2002)	Turkey		CD
Siqueira et al[113] (2016)	Brazil		CD
Saatci et al[106] (2002)	Turkey	Retinal neovascularization	CD
Fuentes-Páez et al[114] (2007)	Spain	Subretinal fibrosis and uveitis syndrome	UC
Munk et al[115] (2016)	United States	Acute macular neuroretinopathy	UC
McClelland et al[116] (2012)	United States	Optic perineuritis	CD
Felekis et al[117] (2010)	Greece	Anterior ischemic optic neuropathy	CD
Mason et al[118] (2002)	United States	Macular edema	CD
De Franceschi et al[119] (2000)	Italy	Dystrophy of the retinal pigment epithelium	CD
Villain et al[120] (2002)	France	Pseudotumor cerebri	CD

CD: Crohn’s disease; IBD: Inflammatory bowel disease; UC: Ulcerative colitis.