FUCHS’ HETEROCHROMIC IRIDOCYCLITIS

Signs and Symptoms

Patients with Fuchs’ heterochromic iridocyclitis present as young adults with variable vision loss, anterior chamber reaction and iris heterochromia.1-3 There appears to be no racial or gender predilection. Initial vision loss is caused by cataract and vitreous opacities. Progressive vision loss can be due to secondary open- or closed-angle glaucoma. Symptoms typical of acute anterior uveitis (e.g., pain, photophobia, lacrimation, redness) are rarely reported.2,4 Approximately 90% of cases are unilateral, but bilateral cases have been reported.1-3,5,6

Heterochromia, long held as the main diagnostic criteria for this condition, is not invariably present. In patients with dark irides, heterochromia may be absent or overlooked.6 In patients with blue eyes, the affected eye will appear darker. If the condition is bilateral, heterochromia will be absent or minimal at best. There is often loss of iris detail.

While clinically apparent heterochromia is not a universal sign, iris stromal atrophy (particularly within the crypts), which is the cause of the heterochromia, is invariably present.4 There is a fragility to the iris and anterior chamber angles, and a high likelihood of hemorrhage following surgery or seemingly insignificant trauma such as gonioscopy due to a fine network of neovascularization.7 These vessels commonly rupture during cataract surgery when the paracentesis is performed, leading to hyphema; such an event is highly suggestive of this condition. Common but often overlooked iris findings are Busacca and Koeppe nodules.3,6

A mild anterior chamber reaction and fine stellate keratic precipitates are hallmarks of this disease.1,4,6,8 The reaction is not true inflammation, but a breakdown of the blood/aqueous barrier, likely from the fragile iris vessels and neovascularization. The keratic precipitates are small to medium in size and nongranulomatous. Posterior synechiae, commonly seen in true uveitis, is not a feature of this condition, nor is cystoid macular edema, as the condition is not predominately inflammatory.9

Cataract and glaucoma occur in approximately 80% and 15% to 25% of cases, respectively.1-4,10,11 While not common, Fuchs’ heterochromic iridocyclitis accounted for over 8% of endogenous uveitis in a large study.12 Fuchs’ is an underdiagnosed cause of uveitis.

Pathophysiology

There is no clear consensus regarding the etiology of Fuchs’ heterochromic iridocyclitis. An infectious etiology has been strongly considered. There has been a significant association between Fuchs’ heterochromic iridocyclitis and ocular toxoplasmosis.5,13-15 However, it is not clear if there is a causal relationship between the conditions.

Further strengthening the assertion of an infectious etiology behind Fuchs’ heterochromic iridocyclitis is the discovery of herpes simplex virus DNA in the aqueous humor of an eye with the condition.16 Recent evidence also points to a possible association with the rubella virus.8,17,18 Additionally, it seems that the Chikungunya virus has been associated.19 An autoimmune etiology has also been proposed due to the association between Fuchs’ heterochromic iridocyclitis and retinitis pigmentosa. Since autoimmune phenomena have been described in patients with retinitis pigmentosa, it is conceivable that it may increase the risk for the development of Fuchs’ heterochromic iridocyclitis.20,21

The cellular response is predominately lymphocytes and plasma cells, along with few mast cells and eosinophils.3 There are rarely posterior synechiae; however, anterior synechiae have been known to occur and contribute to the formation of glaucoma. Causes of glaucoma include secondary angle closure as a result of inflammation with peripheral anterior synechiae, rubeosis, lens-induced angle closure and secondary open-angle glaucoma as a result of recurrent spontaneous hyphema.10

Visually significant cataract occurring secondary to chronic inflammation accounts for the majority of the visual impairment. Vitreous opacities and inflammatory debris as well as advanced glaucoma can also cause vision loss.

Management

Correct diagnosis is especially important, to avoid ineffective treatments and give the clinician an awareness of the prognosis. In many cases, patients with Fuchs’ heterochromic iridocyclitis are initially misdiagnosed with anterior uveitis or pars planitis.3 Though anterior chamber reaction and stellate keratic precipitates characterize the condition, it is not responsive to steroids in any form.8,22 Fuchs’ heterochromic iridocyclitis does not cause a severe anterior chamber reaction. Most eyes have minimal anterior segment response for years, with some becoming entirely cell free.

Many eyes with Fuchs’ heterochromic iridocyclitis receive chronic topical steroid therapy due to misdiagnosis, contributing to cataract formation and glaucoma.23 Chronic, mild anterior chamber reactions can often be tolerated without morbidity and thus a lack of a viable treatment is not detrimental. Unfortunately, the chronic accumulation of keratic precipitates, vitreous debris and cataract over time can diminish vision, with the formation of peripheral anterior synechiae eventually leading to glaucoma.23

Visual rehabilitation can be easily accomplished through cataract extraction, with minimal complications. Eyes with Fuchs’ heterochromic iridocyclitis tolerate phacoemulsification with posterior chamber lens implantation well.24-27 In patients with visually significant vitreous debris, pars plana vitrectomy—either separately or in conjunction with cataract surgery—will benefit most patients.26,28

Glaucoma carries the most risk of significant ocular morbidity in Fuchs’ heterochromic iridocyclitis, and must be managed aggressively. Aqueous suppressants are the topical treatment of choice. Miotics should be avoided.

Prostaglandin analogs should be considered as a last medical option. While the disease often responds well to medical therapy, trabeculectomy is frequently needed. Compared to uncomplicated open-angle glaucoma, the surgical outcome is less favorable and similar to outcome statistics seen in uveitic glaucoma.22 Antimetabolites are used to optimize surgical results.10,11,29

Clinical Pearls

Despite the clinically apparent anterior chamber reaction, do not treat patients with Fuchs’ heterochromic iridocyclitis with topical steroids, as they are ineffective. Accept that no treatment may be the best treatment for the cellular reaction. Instead, concentrate management efforts at the comorbid glaucoma and cataract.

Consider Fuchs’ heterochromic iridocyclitis in patients with anterior uveitis unresponsive to steroid therapy. In fact, unresponsiveness to topical steroids can be a diagnostic sign of Fuchs’ heterochromic iridocyclitis.

Its name notwithstanding, do not rely upon heterochromia to make a diagnosis of Fuchs’ heterochromic iridocyclitis. Many patients will not manifest heterochromia. Instead, examine carefully for iris atrophy (especially within the crypts) and iris nodules.

1. Velilla S, Dios E, Herreras JM, et al. Fuchs’ heterochromic iridocyclitis: a review of 26 cases. Ocul Immunol Inflamm. 2001;9(3):169-75.

2. Fearnley IR, Rosenthal AR. Fuchs’ heterochromic iridocyclitis revisited. Acta Ophthalmol Scand. 1995;73(2):166-70.

3. Jones NP. Fuchs’ Heterochromic Uveitis: a reappraisal of the clinical spectrum. Eye. 1991;5 (Pt 6):649-61.

4. La Hey E, Baarsma GS, De Vries J, et al. Clinical analysis of Fuchs’ heterochromic cyclitis. Doc Ophthalmol. 1991;78(3-4):225-35.

5. Ganesh SK, Sharma S, Narayana KM, et al. Fuchs’ heterochromic iridocyclitis following bilateral ocular toxoplasmosis. Ocul Immunol Inflamm. 2004;12(1):75-7.

6. Arellanes-Garcia L, del Carmen Preciado-Delgadillo M, Recillas-Gispert C. Fuchs’ heterochromic iridocyclitis: clinical manifestations in dark-eyed Mexican patients. Ocul Immunol Inflamm. 2002;10(2):125-31.

7. Ward DM, Hart CT: Complicated cataract extraction in Fuchs’s heterochromic uveitis. Br J Ophthalmol 1967; 51:530-8.

8. Gordon L. Fuch’s heterochromic cyclitis: new clues regarding pathogenesis. Am J Ophthalmol. 2004;138(1):133-4.

9. Tandon M, Malhotra PP, Gupta V, et al. Spectrum of Fuchs uveitic syndrome in a North Indian population. Ocul Immunol Inflamm. 2012;20(6):429-33.

10. Jones NP. Glaucoma in Fuchs’ Heterochromic Uveitis: aetiology, management and outcome. Eye. 1991;5 ( Pt 6):662-7.

11. La Hey E, de Vries J, Langerhorst CT, et al. Treatment and prognosis of secondary glaucoma in Fuchs’ heterochromic iridocyclitis. Am J Ophthalmol. 1993;116(3):327-40.

12. Pivetti-Pezzi P, Accorinti M, La Cava M, et al. Endogenous uveitis: an analysis of 1,417 cases. Ophthalmologica. 1996;210(4):234-8.

13. Schwab IR. The epidemiologic association of Fuchs’ heterochromic iridocyclitis and ocular toxoplasmosis. Am J Ophthalmol. 1991;111(3):356-62.

14. La Heij E, Rothova A. Fuchs’s heterochromic cyclitis in congenital ocular toxoplasmosis. Br J Ophthalmol. 1991;75(6):372-3.

15. Jad A, C Céline T, BahramB, et al. Fuchs’ heterochromic cyclitis: a post-infectious manifestation of ocular toxoplasmosis? International Ophthalmology 2013; 33(2),189-94.

16. Barequet IS, Li Q, Wang Y, et al. Herpes simplex virus DNA identification from aqueous fluid in Fuchs heterochromic iridocyclitis. Am J Ophthalmol. 2000;129(5):672-3.

17. Stunf S, Petrovec M, Žigon N, et al. High concordance of intraocular antibody synthesis against the rubella virus and Fuchs heterochromic uveitis syndrome in Slovenia. Mol Vis. 2012; 18: 2909–14.

18. Suzuki J, Goto H, Komase K, et al. Rubella virus as a possible etiological agent of Fuchs heterochromic iridocyclitis. Graefe’s Archive for Clinical and Experimental Ophthalmology 2010; 248(10):1487-91.

19. Mahendradas P, Shetty R, Malathi J, Madhavan HN. Chikungunya virus iridocyclitis in Fuchs’ heterochromic iridocyclitis. Indian J Ophthalmol. 2010;58(6):545-7.

20. Chowers I, Zamir E, Banin E, et al. Retinitis pigmentosa associated with Fuchs’ heterochromic uveitis. Arch Ophthalmol. 2000;118(6):800-2.

21. Lichtinger A, Chowers I, Amer R. Usher syndrome associated with Fuchs’ heterochromic uveitis. Graefe’s Archive for Clinical and Experimental Ophthalmology 2010;248(10):1481-5.

22. Jones NP. Fuch’s heterochromic uveitis: An update. Surv Ophthalmol 1993; 37(4):253-72.

23. O’Connor GR. Heterochromic iridocyclitis. Trans Ophthalmol Soc UK 1985; 104:219-31.

24. Cheng B, Liu Y. Phacoemulsification in eyes with Fuchs’ heterochromic iridocyclitis. Yan Ke Xue Bao. 2000;16(2):97-8.

25. Budak K, Akova YA, Yalvac I, et al. Cataract surgery in patients with Fuchs’ heterochromic iridocyclitis. Jpn J Ophthalmol. 1999;43(4):308-11.

26. Soheilian M, Karimian F, Javadi MA, et al. Surgical management of cataract and posterior chamber intraocular lens implantation in Fuchs’ heterochromic iridocyclitis. Int Ophthalmol. 1997;21(3):137-41.

27. Kosker M, Sungur G, Celik T, et al. Phacoemulsification with intraocular lens implantation in patients with anterior uveitis. Journal of Cataract & Refractive Surgery 2013; 39(7):1002-1007.

28. Scott RA, Sullivan PM, Aylward GW, et al. The effect of pars plana vitrectomy in the management of Fuchs heterochromic cyclitis. Retina. 2001;21(4):312-6.

29. You Y, Wu Y, Hu S. Surgical management of secondary glaucoma in Fuchs’ heterochromic iridocyclitis. Graefe’s Archive for Clinical and Experimental Ophthalmology 2013; 251(7): 1785-90.