Part 5 • Uveitic Conditions not Caused by Active Infection Chapter 19 Anterior Uveitis

Medical management of glaucoma in patients with JIA is problematic. Aggressive use of topical IOP-lowering agents is warranted. Surgery is required for a number of patients for whom medical management has failed. Laser iridectomy is indicated for glaucoma caused by pupillary block with iris bombé. In patients with secondary glaucoma caused by chronic intraocular inflammation the success of traditional surgery with trabeculectomy is poor.55 Filtering devices such as Molteno implants may improve the prognosis. Cyclocryotherapy should only be used when other surgical procedures have failed to control the pressure.

Band keratopathy is seen in 77% of patients with severe JIA-associated iridocyclitis.41 This band keratopathy can be treated with chemical chelation with topical application of 0.37 M ethylenediamine tetraacetic acid solution after de­ bridement of the epithelium with 70% isopropyl alcohol and scraping. The excimer laser may have a role in the management of this complication in the future. Keratoconjunctivitis sicca can also occur in JIA. In a study of 64 patients with JIA, 12.5% complained of dry eye with lower Schirmer test results and tear break-up times than age-and gendermatched controls.56

Prognosis is related to early diagnosis and meticulous treatment of ocular inflammation and management of secondary complications. Because ocular inflammation does not always mirror joint disease, routine ophthalmologic examinations at least every 3 months are recommended.57 This makes sense, as complications and vision loss are common. In a retrospective cohort study of 75 patients with JIA, the incidence of any ocular complication was 0.33 per eye-year.58 Rates of vision loss to 20/50 or worse and 20/200 or worse were 0.10 per eye-year and 0.08 per eye-year, respectively. Risk factors included anterior chamber flare 1+ or greater and elevated IOP. Immunosuppressive drug therapy reduced the rates of complications, including hypotony and blindness.

Psoriatic arthropathy

Psoriasis is a skin disease caused by hyperproliferation of the epidermis with resultant scaling. Uveitis occurs predominantly in patients who develop arthropathy. About 20% of patients with psoriasis develop psoriatic arthropathy, and about 20% of these patients develop uveitis, sacroiliitis, and ascending spine disease.59 The arthropathy usually involves the distal joints of the hands and feet as well as the sacroiliac joints. The uveitis predominantly involves the anterior segment of the eye and is similar to HLA-B27-associated disease. Because psoriasis is a common disorder, not all anterior uveitis that occurs in patients with psoriasis will be causally related, especially if the patient does not have arthritis. The psoriasis and arthropathy in these patients have been treated separately. Anti-TNF agents have also been used to treat both components of the disease.60 The uveitis tends to respond well to standard therapy with topical corticosteroids and a drop to induce cycloplegia and mydriasis.

Inflammatory bowel disease

Patients with both ulcerative colitis and Crohn’s disease can develop uveitis.61,62 About 5% of patients with ulcerative colitis will develop ocular disease. Conjunctivitis, episcleritis, and anterior uveitis are most commonly described;

however, posterior uveitis may also occur. Similar ocular inflammatory disease has been associated with Crohn’s disease. The ophthalmologist should ask patients with anterior uveitis whether they have recurrent diarrhea, bloody diarrhea, or abdominal cramping. Although the uveitis often responds to therapy with topical corticosteroids, early diagnosis of inflammatory bowel disease will lead to prompt treatment for the gastrointestinal complications that frequently occur. Similar to other spondyloarthropathies, anti-TNF agents are now used in the management of the disease. The effect on uveitis is less well documented in clinical trials.

Whipple’s disease

Whipple’s disease is a chronic infectious disease caused by Tropheryma whipplei that has been associated with uveitis.63 Now that the causative organism has been identified, the description of this disease has been moved to the chapter on bacterial and fungal disease (Chapter 9).

Disease associations

Fuchs’ heterochromic iridocyclitis

The association of iris heterochromia and cataract was initially described by Lawrence in 1843.64 In 1906, Fuchs65 described seven patients with heterochromic iridocyclitis, and later described 38 patients with the disease and reported on the pathologic features of six eyes. The classic hallmark of Fuchs’ heterochromic iridocyclitis is, as the name suggests, iris heterochromia (Fig. 19-4A and B). However, this classic finding may be difficult to perceive. It is easiest to see in blue-eyed patients, in whom the affected eye appears more intensely blue.66 In addition, 7–15% of patients have bilateral involvement and no obvious heterochromia. A more consistent finding appears to be blurring of the iris stroma and loss of detail and density of the iris surface that can only be seen on careful slit-lamp biomicroscopic examination.66,67 Fuchs observed that most patients with this disorder develop cataracts.

The typical patient is young and presents with iris heterochromia and a mild disturbance of vision. Pain and redness are rare. Slit-lamp examination shows small stellate keratic precipitates (KPs) with fine filaments that are uniformly scattered over the endothelium, unlike most other occurrences of anterior uveitis in which the precipitates occur predominantly on the lower half of the cornea. Anterior chamber inflammation is mild, and low-grade vitritis may be seen. The posterior segment of the eye is usually unaffected, although cystoid macular edema has been reported in a few patients. Abnormal vessels bridging the anterior chamber angle are frequently described, but iris neovascularization and neovascular glaucoma are rare.68 It is well documented that hyphema is likely to occur after intraocular surgery. Amsler69 first noted the occurrence of hyphema after paracentesis. Anterior chamber paracentesis was initially proposed as a diagnostic test for Fuchs’ heterochromic iridocyclitis, but appears unwarranted for this purpose.68

Many patients with Fuchs’ heterochromic iridocyclitis are unaware of their disease until their vision decreases because of cataract or progressive glaucoma. Rarely, vitreous

inflammation is severe enough to cause floaters. The presence of fine, evenly distributed KPs in a white eye with mild anterior chamber cells and flare, cataract, and increased intraocular pressure should suggest the diagnosis. Patients often note that one iris has been lighter in color for many years. Brown eyes become less brown and blue eyes appear more blue with this disorder, because the heterochromia is due to a loss of anterior iris pigment. Gray eyes may appear green.

The differential diagnosis of Fuchs’ heterochromic iridocyclitis includes disorders that produce iris heterochromia. Malignant melanoma of the iris, Horner’s syndrome, and chronic anterior uveitis with iris atrophy caused by infections such as herpes zoster should all be considered. In addition, Posner–Schlossman syndrome and neovascular glaucoma may cause ocular disease that looks like Fuchs’ heterochromic iridocyclitis.

Etiology

A number of researchers have hypothesized an infectious cause for Fuchs’ heterochromic iridocyclitis. Fuchs described peripheral chorioretinal scars in some patients with this disease. Several authors have associated Fuchs’ heterochromic iridocyclitis with toxoplasmosis (Fig. 19-5). Ocular toxoplasmosis may cause fine KPs and anterior uveitis and mimic Fuchs’ heterochromic iridocyclitis. This would explain why many patients with Fuchs’ heterochromic iridocyclitis lack findings of toxoplasmosis. Others suggest that infection with Toxoplasma may be causally related to the development of the disorder. Chorioretinal scars consistent with ocular histoplasmosis have also been noted, but a causal relationship between infectious agents and Fuchs’ heterochromic iridocyclitis is unproven. Others have proposed that a lack of normal sympathetic innervation and neurogenic factors cause the findings associated with the disease, but again these associations are unproven.68

Recently, investigators have suggested an association of rubella virus with Fuchs’ heterochromic iridocyclitis. In one study, rubella virus – but not herpes simplex virus, varicella zoster virus, or toxoplasmosis – was associated with the disease.70 Antibody against rubella was identified in the aqueous humor of 13 of 14 patients studied; antibody against the other infectious agents was not found. In another study, antibody against rubella virus using nested PCR was found in all 52 eyes with Fuchs’ heterochromic cyclitis.71

Figure 19-5.  Chorioretinal scar consistent with toxoplasmosis observed in the patient shown in Figure 19-4. (Courtesy of Rubens Belfort Jr, MD.)

The finding of infiltrating plasma cells and lymphocytes on pathologic examination of ocular specimens from patients with Fuchs’ iridocyclitis confirms an inflammatory cause for the disease.72 Electron microscopic examination of iris biopsy specimens showed both a reduction in the number of stromal melanocytes and a decrease in melanosome size.73 Plasma cells, mast cells, and lymphocytes were present in the tissue, but no infectious organisms were seen. Although Fuchs’ heterochromic iridocyclitis may be a single pathologic entity with a single cause, much of the evidence suggests that many occurrences represent a common ocular response that can develop from a variety of etiologic insults.

Treatment and prognosis

Fuchs’ heterochromic iridocyclitis is generally chronic. Although therapy with topical corticosteroids can reduce the clinical signs of inflammation, long-term topical therapy is often unnecessary and may serve only to hasten cataract formation and induce glaucoma in steroid responders. Cataracts can be safely removed in patients with Fuchs’ heterochromic iridocyclitis; however, the glaucoma associated with the disease may not be easily controlled and can result in significant and permanent visual loss. Uveitis in these patients must be controlled. Although medications can control the glaucoma, surgery is often required but is fraught