Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis (UC). Both are designated as intractable diseases (specific diseases) by the Ministry of Health, Labour and Welfare.
Crohn’s disease is a condition that causes discontinuous, transmural granulomatous inflammation throughout the entire gastrointestinal tract from the mouth to the anus, with a predilection for the ileocecal region. It typically develops in young adults and presents with intestinal symptoms such as chronic diarrhea, abdominal pain, fever, and anal fistulas, as well as various extraintestinal manifestations involving the eyes, joints, skin, and hepatobiliary system. Ulcerative colitis is a nonspecific inflammatory disease that forms ulcers in the mucosa and submucosa of the colon (especially the rectum), extending continuously toward the proximal side, with main symptoms of mucous bloody stools, diarrhea, and fever. Both diseases follow a chronic course with repeated remissions and relapses.
IBD-associated uveitis is positioned as a form of the spondyloarthritis spectrum (ankylosing spondylitis, reactive arthritis, psoriatic arthritis, IBD-associated). According to epidemiological data from the uveitis clinical practice guidelines, IBD-associated uveitis accounts for approximately 0.6–0.7% of all uveitis cases1). Although rare, it is a complication that should always be considered in patients with intestinal disease.
The frequency of ocular complications is less than 10% in ulcerative colitis, and acute anterior uveitis (AAU) is observed in 5–15% of Crohn’s disease patients. Cases strongly associated with HLA-B27 tend to present with recurrent AAU1). In recent years, with the widespread use of biologic agents, an increasing number of cases can be managed by simultaneously controlling both intestinal and ocular inflammation2).
Yes, it can occur. In Crohn’s disease, acute anterior uveitis occurs in 5–15% of patients, and ocular complications occur in less than 10% of patients with ulcerative colitis. If redness, eye pain, or photophobia appear suddenly, please see an ophthalmologist promptly.
Acute anterior uveitis presents with sudden onset of redness, eye pain, photophobia, and blurred vision. Posterior segment lesions cause floaters, metamorphopsia, and decreased visual acuity. In some cases, ocular symptoms precede active intestinal disease.
Anterior Segment (Most Common)
Acute anterior uveitis (AAU): The most common ocular complication. Findings include fibrin exudation, anterior chamber cells, and flare.
Hypopyon: Occurs in HLA-B27 positive cases. Unlike Behçet’s disease, nivô formation is rare.
Posterior synechiae: Caused by recurrent inflammation. Prevented by early use of mydriatics.
Corneal marginal ulcer: May occur with active IBD.
Posterior Segment
Chorioretinitis: Exudative changes in the posterior pole.
Retinal vasculitis: Fluorescein angiography shows leakage from vessel walls.
Serous retinal detachment: Due to leakage from active inflammation.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)-like lesions: Rarely associated.
Central retinal vein occlusion (CRVO): Associated with ocular ischemia.
Adnexa and Sclera
Episcleritis: Mild redness and irritation. Course is self-limiting.
Scleritis: Deep vascular dilation, tenderness, and throbbing eye pain. Rarely progresses to necrotizing scleritis.
Conjunctivitis and blepharitis: Mild conjunctival injection and eyelid edema.
Secondary Complications
Band keratopathy: Calcium deposition at the corneal limbus after recurrent anterior inflammation.
Complicated cataract: Due to chronic inflammation and long-term steroid use.
Secondary glaucoma: Increased intraocular pressure due to posterior synechiae, peripheral anterior synechiae, and pupillary block.
Cystoid macular edema and epiretinal membrane: Late complications of chronic inflammation.
In Crohn’s disease, bilateral and recurrent AAU is common. Ocular inflammation often flares in parallel with intestinal disease activity, but an important feature is that ocular inflammation can also occur during remission. In some cases, ocular symptoms precede intestinal symptoms, and IBD may be undiagnosed at the initial ophthalmology visit.
In many cases, ocular inflammation flares during active intestinal disease, but it can also occur independently during remission when intestinal disease is quiet. It is important not to judge based on eye symptoms alone and to collaborate with a gastroenterologist.
The development of IBD-associated uveitis involves a combination of genetic predisposition, immune abnormalities, and environmental factors.
For a definitive diagnosis of IBD-associated uveitis, gastrointestinal evaluation (endoscopy and biopsy) by a gastroenterologist is essential1). Ocular findings are not specific, and the basic approach is a combination of exclusion diagnosis and systemic assessment.
Basic screening recommended by the uveitis clinical practice guidelines1):
| Disease | Key differentiating features |
|---|---|
| Intestinal Behçet’s disease | Morphology of mucosal ulcers (deep penetrating ulcers), oral aphthae, HLA-B51 |
| HLA-B27-associated AAU (primary) | No spondylitis/sacroiliitis or IBD diagnosis |
| Sarcoidosis | Granulomatous uveitis, hilar lymphadenopathy, elevated ACE |
| Reactive arthritis (Reiter syndrome) | Triad of preceding infection, arthritis, urethritis |
| Psoriatic uveitis | Skin lesions, nail changes, HLA-A2 |
| Infectious endophthalmitis | Rapid course, vitreous opacity |
The key differentiating points are the morphology of intestinal ulcers and the characteristics of oral aphthae. Crohn’s disease presents with discontinuous longitudinal ulcers, while Behçet’s disease forms deep, perforating solitary ulcers. HLA-B51 is associated with Behçet’s disease. Ocular findings: in Behçet’s disease, hypopyon tends to form a fluid level and is mobile.
Treatment of IBD-associated uveitis involves two pillars: local ocular therapy and systemic therapy (simultaneous control of the intestine and eye).
Standard treatment for acute anterior uveitis1):
Systemic treatment is performed in collaboration with a gastroenterologist. Control of intestinal lesions is directly linked to stabilization of ocular inflammation.
| Drug category | Representative drug | Main indication |
|---|---|---|
| 5-ASA preparations | Mesalazine (Pentasa®, Asacol®) | First-line for UC |
| Corticosteroids | Prednisolone 0.5–1 mg/kg/day, tapered | Induction of remission in active phase |
| Immunosuppressants | Azathioprine 2–2.5 mg/kg/day, methotrexate, cyclosporine, tacrolimus | Maintain remission, reduce steroids |
| TNF-α inhibitors | Infliximab (Remicade®), adalimumab (Humira®) | Moderate to severe IBD + ocular involvement |
Details of TNF-α inhibitors2):
TNF-α inhibitors such as infliximab and adalimumab have been reported to simultaneously suppress intestinal and ocular inflammation. Adalimumab is approved for non-infectious uveitis and is recommended for active use in IBD-associated ocular inflammation2).
The pathogenesis of IBD-associated uveitis involves a common axis between the intestinal immune system and the ocular immune system.
The “homing hypothesis” has been proposed, in which lymphocytes activated in the intestinal mucosa enter the systemic circulation via the α4β7 integrin-MAdCAM-1 pathway and are recruited to ocular tissues. The intestinal mucosa and the eye are thought to communicate through a common mucosal immune system (MALT)3).
TNF-α, IL-23, and IL-17 (Th17 axis) are overexpressed in both intestinal and ocular tissues, leading to chronic inflammation. IL-23 induces Th17 cells, causing disruption of the intestinal epithelial barrier and intraocular inflammation through a common mechanism4).
HLA-B27 induces aberrant antigen presentation of self-peptides and is a common risk allele for spondyloarthritis and IBD-associated uveitis. In HLA-B27-positive IBD patients, the recurrence rate of AAU is significantly higher1).
In IBD, dysbiosis of the gut microbiota disrupts immune tolerance, leading to overactivation of mucosal immunity. The relationship between gut microbiota and ocular inflammation has recently gained attention, with reports that reduced diversity of gut microbiota in IBD patients correlates with the frequency of ocular complications3).
JAK inhibitors such as tofacitinib and upadacitinib are being studied for their effects on both IBD and uveitis. They are approved for ulcerative colitis, and case reports on their efficacy for ocular inflammation are accumulating4).
The anti-α4β7 integrin antibody vedolizumab has intestinal selectivity specific to IBD, but its effect on ocular complications is reported to be limited compared to TNF-α inhibitors. It has been suggested that it may not be the first choice when IBD-associated ocular lesions are present3).
Modulation of gut microbiota through probiotics and fecal microbiota transplantation (FMT) is being applied in IBD treatment, and exploratory studies are being conducted on its effects on ocular inflammation.
