Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

Anterior nongranulomatous uveitis may result from direct or indirect penetrating or nonpenetrating trauma to the eye. Ocular trauma encompasses surgical procedures, laser applications, and violence to the eyes.23

Treatment of traumatic uveitis is closely related to the actual causative aetiology.

INFECTIOUS CAUSES

Several systemic infectious diseases can be associated with anterior uveitis that is more often non-granulo- matous than granulomatous. They include rickettsioses, West Nile virus infection, dengue fever, Rift Valley fever, chikungunya, and leptospirosis. Leptospirosis was found to be the most common cause of nongranulomatous uveitis in South India.41

Mild, bilateral non-granulomatous, anterior uveitis is common in systemic viral illnesses including mumps, measles, varicella, and mononucleosis. Patients typically are asymptomatic, and the uveitis is self-limited.

Poststreptococcal syndrome uveitis should be considered in the differential diagnosis of patients with bilateral anterior non-granulomatous uveitis, especially those at risk for streptococcal infections such as children and young adults. Diagnosis is confirmed by detection of high anti-streptococcal lysin O titres.42

IDIOPATHIC ANTERIOR UVEITIS

Idiopathic anterior uveitis is the most common form of anterior uveitis seen in nearly 50% of cases.1 Patients have anterior segment inflammation that is not attributed to any defined clinical syndromes, lack systemic diseases association and are HLA-B27 negative. A thorough systemic examination is done to rule out relevant systemic diseases, such as spondyloarthropathies, as well as other noninfectious or infectious causes. Patients present with complaints of redness, pain photophobia and decreased vision. Ocular examination shows ciliary congestion, presence of cells and flare in the anterior chamber, nongranulomatous KPs, with or without posterior synechiae (Figure 11). Presence of hypopyon and fibrin is rare in idiopathic variety and if present should suggest other entities like HLA-B27 associated anterior uveitis. Onset of disease in an old patient should raise

Figure 11: A 26-year-old man presented with a 4-day history of pain, redness, and photophobia in his right eye. It was his first attack (A). There were mild circumcorneal ciliary congestion, 3+ cells in the anterior chamber and few non-granulomatous keratic precipitates. Results of systemic evaluation were negative leading to a diagnosis of idiopathic anterior nongranulomatous uveitis. The patient was treated with topical betamethasone and mydriatics

the possibility of masquerade syndrome.

Topical corticosteroids are given to control intraocular inflammation. Mydriatics and cycloplegics are usually prescribed to prevent development of posterior synechiae and to relieve pain caused by ciliary muscle spasm.

KEY POINTS

1.The distinction between anterior non-granulomatous and anterior granulomatous uveitis is of utmost importance in orienting the work-up and differential diagnosis, although a granulomatous uveitis may initially present as non-granulomatous.

2.Anterior non-granulomatous uveitis is primarily characterised by the presence of very fine keratic precipitates that appear as dust. There are no iris nodules in non-granulomatous uveitis.

3.HLA-B27 AAU occurs most often in young males. Inflammation is typically sudden in onset and unilateral, but involvement of the contralateral eye usually occurs with subsequent attacks that can swing from one eye to the other. There may be fibrinous clotting or hypopyon in cases with severe inflammation.

4.HLA-B27 AAU may be idiopathic or associated with one of the seronegative spondyloarthropahies, which include ankylosing spondylitis, Reiter’s syndrome (reactive arthritis), psoriatic arthritis, inflammatory bowel diseases, and undifferentiated spondyloarthropathy.

5.In patients with HLA-B27 AAU, prompt initiation of

treatment with topical steroids is mandatory to shorten the duration of the attack, prevent complications, and improve visual prognosis.

6.Juvenile idiopathic arthritis (JIA) is the most common cause of childhood anterior uveitis in western countries. Inflammation is typically insidious in onset, chronic, and bilateral. Band-shaped keratopathy, cataract, and glaucoma are common complications of JIA.

7.The asymptomatic nature of JIA-associated uveitis necessitates the need for periodic ocular screening of patients with JIA. Early diagnosis of uveitis is very important for successful therapy.

8.Although HLA-B27 AAU and JIA are the most common specific aetiologies of anterior non-granulomatous uveitis, numerous other non-infectious and infectious conditions should be considered in the differential diagnosis.

9.All relevant non-infectious and infectious diseases should be ruled out before a diagnosis of idiopathic uveitis can be made. Idiopathic anterior uveitis is the most common form of anterior uveitis.

REFERENCES

1.Chang JH, Wakefield D. Uveitis: a global perspective. Ocul Immunol Inflamm 2002;10:263-79.

2.Tran VT, Auer C, Guex-Crosier Y, Pittet N, Herbort CP. Epidemiological characteristics of uveitis in Switzerland. Int Ophthalmol 1994-1995;18:293-8.

3.Khairallah M, Yahia SB, Ladjimi A, Messaoud R, Zaouali S, Attia S, et al. Pattern of uveitis in a referral center in Tunisia, North Africa. Eye 2007;21:33-9.

4.McCannel CA, Holland GN, Helm CJ, et al. Causes of Uveitis in the general practice of ophthalmology. UCLA Community-based Uveitis Study Group. Am J Ophthalmol 1996;121:35–46.

5.Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol 1992;76:137–41.

6.Brewerton DA, Caffrey M, Nicholls A, et al. Acute anterior uveitis and HL-A 27. Lancet 1973;2(7836):994–6.

7.Henderly DE, Genstler AJ, Smith RE, Rao NA. Changing patterns of uveitis. Am J Ophthalmol 1987;103:131–6.

8.Biswas J, Narain S, Das D, Ganesh SK. Pattern of uveitis in a referral uveitis clinic in India. Int Ophthalmol 1996- 97;20:223–8.

9.Linssen A, Rothova A, Valkenburg HA, et al. The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLA-B27. Invest Ophthalmol Vis Sci 1991;32:2568–78.

10.Monnet D, Breban M, Hudry C, et al. Ophthalmic findings and frequency of extraocular manifestations in patients with HLA-B27 uveitis: a study of 175 cases. Ophthalmology 2004;111:802–9.

11.Wakefield D, Wright J, Penny R. HLA antigens in uveitis. Hum Immunol 1983;7:89–93.

12.Chang JH, , McCluskey P, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol 2005;50:364–88.

13.Rosenbaum JT. HLA B27-associated diseases. In: Pepose JS, Holland GN, Wilhelmus KR (Eds): Ocular Infection and Immunity. St Louis, Mosby-Yearbook, 1996;475–84.

14.Keat A, Thomas B, Dixey J, et al. Chlamydia trachomatis and reactive arthritis: the missing link. Lancet 1987;1:72– 4.

15.Saari KM, Laitinen O, Leirisalo M, Saari R. Ocular inflammation associated with Yersinia infection. Am J Ophthalmol 1980;89:84–95.

16.Power WJ, Rodriguez A, Pedroza-Seres M, Foster CS. Outcomes in anterior uveitis associated with the HLA-B27 halotype. Ophthalmology 1998;105:1646–51.

17.Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Physician 2004;69:2853-60.

18.Rosenbaum JT. Acute anterior uveitis and spondyloarthropathies. Rheum Dis Clin North Am 1992;18:143-51.

19.Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: an overview. Ann Rheum Dis 2002;61(suppl 3):8-18.

20.Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996;80:332–6,

21.Amor B. Reiter’s syndrome. Diagnosis and clinical features. Rheum Dis Clin North Am 1998;24:677-95.

22.Yu DT, Peng TF. Reiter’s syndrome. In: Ruddy S, Harris ED Jr, Sledge CB (Eds). Kelley’s Textbook of Rheumatology (6th edn). Philadelphia: Saunders, 2001;1055-70.

23.Foster CS, Vitale AT (Eds). Diagnosis and Treatment of Uveitis. WB Saunders Company, 2002, 900 p.

24.Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78.

25.Paiva ES, Macaluso DC, Edwards A, Rosenbaum JT. Characterization of uveitis in patients with psoriatic arthritis. Ann Rheum Dis 2000;59:67-70.

26.De Keyser F, Elewaut D, De Vos M, De Vlam K, Cuvelier C, Mielants H, et al. Bowel inflammation and the spondyloarthropathies. Rheum Dis Clin North Am 1998; 24:785-813.

27.Lyons JL, Rosenbaum JT. Uveitis associated with inflammatory bowel disease compared with Uveitis associated with spondyloarthropathy. Arch Ophthalmol 1997;115: 61- 4.

28.Petty RE, Southwood TR, Baum J, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 1998;25:1991–4.

29.Khairallah M, Attia S, Zaouali S, Yahia SB, Kahloun R, Messaoud R, et al. Pattern of childhood-onset uveitis in a referral center in Tunisia, North Africa. Ocul Immunol Inflamm 2006;14(4):225-31.

30.Kanski JJ. Juvenile arthritis and uveitis. Surv Ophthalmol 1990;34:253–67.

31.Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767-78.

32.Kanski JJ, Petty RE. Chronic childhood arthritis and uveitis. In: Pepose JS, Holland GN, Wilhelmus KR (Eds): Ocular Infection and Immunity. St Louis, Mosby, 1996, pp 485–93.

33.Kotaniemi K, Savolainen A, Karma A, Aho K. Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol 2003;48:489–502.

34.Lundvall A, Zetterstrom C. Cataract extraction and intraocular lens implantation in children with uveitis. Br J Ophthalmol 2000;84:791-3.

35.Waheed NK, Miserocchi E, Foster CS. Ocular concerns in juvenile rheumatoid arthritis. Int Ophthalmol Clin 2001; 41:223–34.

36.Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huseyin Altunbas H, Urgancioglu M. Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol 2004;138:373-80.

37.Kadanoff R, Lipps B, Khanna A, Hou S. Tubulointerstitial

Nephritis With Uveitis (TINU): A Syndrome Rheumatologists should Recognize: A Case Report and Review of the Literature. J Clin Rheumatol 2004;10:25-7.

38.Oen K. Comparative epidemiology of the rheumatic diseases in children. Curr Opin Rheumatol 2000;12:410-4.

39.Khalil MK, Lorenzetti DW. Lens-induced inflammation. Can J Ophthalmol 1986;21:96-102.

40.Moorthy RS, Valluri S, Jampol LM. Drug-induced uveitis. Surv Ophthalmol 1998;42:557-70.

41.Rathinam SR.Ocular manifestations of leptospirosis. J Postgrad Med 2005;51(3):189-94.

42.Ur Rehman S, Anand S, Reddy A, Backhouse OC, Mohamed M, Mahomed I, et al. Poststreptococcal syndrome uveitis: a descriptive case series and literature review. Ophthalmology 2006;113:701-6.

Inflammation of uveal tissue may involve any part of the uvea namely iris, ciliary body and choroid. Based on the primary location of inflammation, uveitis is subcategorized into four major subgroups, anterior, intermediate, posterior and panuveitis.1-4 Anterior uveitis is the inflammation of iris and/or ciliary body. It is characterized by circumcorneal congestion, keratic precipitates, flare and cell floating in the anterior chamber, iris nodules, anterior or posterior synechiae and hypopyon. Based on the slit lamp examination the anterior uveitis can be further identified as Non granulomatous or Granulomatous uveitis. Granulomatous uveitis is usually less acute than the nongranulomatous form. Keratic precipitates (KP), made of clusters of white blood cells on the corneal endothelium are seen as “mutton-fat” deposits or finer granulomatous deposits as opposed to dust in non-granulomatous uveitis (Figure 1A) . Inflammatory cells collect nodules over the iris, named as Koeppe’s nodules (clusters of cells on the pupillary border of the iris) (Figure 1B) or Busacca’s nodules (clusters of cells on the anterior iris surface or within the iris) (Figure 1C). Granulomatous uveitis can further be divided into acute vs chronic, unilateral vs bilateral, infectious vs non infectious and anterior vs granulomatous panuveitis. Examples for each sub classification of granulomatous uveitis are given in Table 1. Sometimes these classifications help the clinician to arrive at a specific aetiological diagnosis.1-4

SARCOIDOSIS

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology, most commonly affecting the

middle aged. As it can involve any organ system, the clinical presentation is often variable.5-7 It may present with erythema nodosum, a symmetrical hilar lymphadenopathy, pulmonary infiltration, peripheral lymph node enlargement, hepatosplenomegaly and arthritis. The heart, liver, spleen, salivary glands, muscles, bones, kidneys, and central nervous system

Table 1: Common clinical examples of anterior granulomatous uveitis according to their onset characteristics

Few entities like sarcoidosis, tuberculosis and syphilis can either present as granulomatous or non-granulomatous type.

Figures 1A-C: Clinical features of anterior granulomatous uveitis (A) Mutton-fat keratic precipitates. (B) Nodules on the pupillary border of the iris known as Koeppe nodules.

(C) Nodules on the iris surface or iris stroma are known as Busacca nodules

may also be involved. Bone involvement is rarely noted as small destructive cystic lesions in the distal ends of the phalanges, metacarpals, and metatarsals.

Figures 2A and B: (A) A 30-year-old woman presented with acute granulomatous anterior uveitis with normal fundus. Keratic precipitates are seen all over the cornea and some are preferentially seen near the angle. Mantoux was negative, Chest X-ray showed hilar lymphadenopathy. ACE was elevated to 89 IU/units (Normal range is 30-53 units). (B) Cystic lesions in the distal ends of the phalanges were seen on X-ray. Patient was treated with topical and oral steroids

The frequency of ocular involvement ranges from 26 to 50 percent. In general, the ocular involvement is seen early in the course, systemic disease may be seen after several years of ophthalmic involvement. Sarcoidosis may present as anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis. Anterior uveitis is usually chronic and of the granulomatous type. Mutton fat keratic precipitates are seen all over the cornea and some are preferentially seen near the angle (Figure 2). In addition, iris nodules, posterior synechiae, cataract and glaucoma are commonly seen in sarcoidosis.5

Because of its nonspecific presentation, the diagnosis of sarcoidosis can be challenging. The initial

evaluation of patients with sarcoidosis aims to confirm the diagnosis, assess the severity of involvement, identify a stable versus progressive disease, and to judge whether therapy will benefit the patient. Diagnosis relies on demonstration of non caseating granuloma by tissue biopsy. However in cases of suspected sarcoidosis where affected tissue is not available to biopsy, supportive evidence can be obtained through non-invasive investigations including serum angiotensin converting enzyme (ACE) and lysozyme analysis. ACE is elevated in 60-90 percent of patients during active systemic sarcoidosis. Specificity and sensitivity of this parameter are low as a normal serum ACE does not exclude the diagnosis and an elevated serum ACE is seen in other disorders such as leprosy, chronic pulmonary disease, rheumatoid arthritis, spondylitis, primary biliary cirrhosis, tuberculosis, and diabetes mellitus. ACE levels usually are followed as a marker of disease activity rather than for diagnostic purposes. Chest X-ray, chest computerized tomography (C-T), X-ray of phalanges, gallium scintillography, pulmonary function tests, bronchoalveolar lavage, and measurement of serum and urinary calcium are other useful investigations. Mild anterior uveitis is treated by topical steroids and cycloplegics. Systemic steroids are indicated in anterior uveitis not responding to topical steroids. The most common manifestations of posterior segment and the treatment are discussed in subsequent chapters. Prognosis of systemic disease is highly variable, two thirds of cases resolve spontaneously, one third progress to long-term disease, and 5 percent result in fatality. However anterior uveitis due to sarcoidosis carries good prognosis.5-7

TUBERCULOSIS

Tuberculosis is a chronic granulomatous disease, caused by the intracellular acid fast bacillus

Mycobacterium tuberculosis or related members of the TB complex. Ocular tissues could be affected either by a direct invasion of M. tuberculosis or due to the immunologic response towards the antigens.8-10 Ocular tuberculosis is a form of extrapulmonary tuberculosis. The clinical manifestations are diverse and depend on the immunologic, bacteriologic, and epidemiologic factors.8,11 Tuberculous uveitis often presents as a chronic granulomatous disease that causes mutton-fat

keratic precipitates, iris nodules, and posterior synechiae.12 Other reported presentations include phlyctenular conjunctivitis, sclerokerato-uveitis, and anterior chamber granulomas. The posterior segment findings are more characteristic, with the retinochoroiditis and choroidal granulomas being very common clinical features.8-13 However, tuberculosis should be considered in cases of chronic anterior granulomatous uveitis even in the absence of posterior segment involvement12 (Figures 3 and 4). Likewise absence of clinically evident pulmonary TB does not rule out the possibility of ocular TB, as approximately 60 percent of patients with extra pulmonary TB have no evidence of pulmonary TB14 (Figure 5). A complete systemic work-up is mandatory as patients with ocular tuberculosis may sometimes present with other forms of extrapulmonary tuberculosis such as tubercular lymphadenitis (Figure 3) or intracranial tuberculoma (Figure 5). The diagnostic work-up includes complete physical examination, PPD test, and chest radiograph. In addition, smear and culture of biological specimen and histopathology are done whenever possible. The diagnosis remains presumptive unless it is microbiologically proven.3,8-17 On several occasions, definitive diagnosis is difficult in ophthalmology because of paucity of material available for laboratory work-up. Ocular tuberculosis needs a specific treatment, and routine uveitis treatment with steroids in the absence of antitubercular treatment (ATT) could be sight or life threatening. A standard course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol followed by 4 months of rifampicin and isoniazid) is usually recommended. The ocular inflammation usually resolves completely (Figure 4C and 5C) within 6 weeks of starting ATT and recurrence is rare, unlike leprosy where relapses are more common even after completing treatment. Tubercular granulomas should be differentiated from other granulomatous lesions such as syphilis, sarcoidosis, fungal lesions and masquerade syndromes.1-4 It is important to recognize atypical manifestations which can only be picked-up with a high index of suspicion.13

LEPROSY

Leprosy is a chronic granulomatous disease, caused by the intracellular acid fast bacillus Mycobacterium lepra. Multibacillary Leprosy causes three different forms of

uveitis.23-31 The first form is typically acute and may produce granulomatous keratic precipitates, posterior synechiae, hypopyon, and occasionally conjunctival leproma (Figure 6). It results from a type II immune reaction where the patient has abundant amount of antibodies and the antigens. These antibodies are not protective in nature and deposition of the antigen antibody complex lead on to recurrent inflammatory episodes namely erythema nodosum leprosum.22,23 Anterior granulomatous uveitis belongs to this reactional status. The second form of ocular leprosy is neuroparalytic uveitis in which large numbers of lepra bacilli are loaded in the uveal tract during initial bacteremia, Slow degeneration of the nerve leads to dilator muscle atrophy.26 The third form of uveal

involvement is presence of iris pearls or lepra pearls made of clumps of both dead and live lepra bacilli. They are seen as small white grains of sand on the iris surface. These iris pearls may dislodge into the anterior chamber forming a pseudohypopyon15 (Figure 6C). Better prognosis seen in recent years is attributed to the most effective multidrug regimen for the treatment of leprosy and it appears to reduce the risk of ocular complications.24 The patients with type 2 reaction may require an aggressive use of topical and oral corticosteroids, mydriatic agents and oral anti-leprosy treatment. Multidrug first line therapy includes three drugs for six months, Rifampicin (600 mg first day of every month), Clofazimine (300 mg first day of every month and followed by 50 mg/day), and Dapsone

Figures 6A-C: (A) A 60-year-old man with lepromatous leprosy with nasal bone fracture and (B) A conjunctival leproma in right eye. (C) Lepra pearls in left eye. Patient was started on multidrug antileprosy treatment

(100 mg/day). Unlike tuberculosis progressive ocular inflammation is seen in some patients even after completion of multidrug treatment.18-22

SYPHILIS

Syphilis may present in a wide variety of uveitic forms and may mimic various other diseases. Therefore, misdiagnosis is common and a high index of suspicion is needed for an accurate diagnosis.32-34 Uveitis is more often a manifestation of secondary syphilis (Figure 7A). However physical examination may or may not reveal skin lesions of secondary syphilis and the uveitis may be the sole clinical manifestation. It may present as an acute unilateral or bilateral anterior uveitis or panuveitis with hyphema or hypopyon. Iris roseolae are engorged vascular tufts of the middle third of the iris, it progress to iris papules (Figure 7B). These may later evolve to vascularised iris nodules. Episcleritis, scleritis, interstitial keratitis may also be the presenting sign in syphilis, with no other distinguishing feature. Nontreponemal tests such as VDRL or RPR are used as screening tests, FTA-ABS and TPHA are more specific and reactive in 98 to 100 percent of untreated patients. Treatment with 2.4 × 106 units of benzathine penicillin remains the treatment of choice for syphilis. Topical steroids and mydriatics are added depending upon the severity and anatomical location of uveitis.32-34

VIRAL INFECTIONS

Numerous viruses have been suggested as causes of anterior uveitis. They include Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), Cytomegalovirus (CMV, Epstein-Barr Virus (EBV), and Human T-cell lymphotropic virus, type 1 (HTLV-1).35-38

HSV INFECTION

Anterior uveitis secondary to HSV typically occurs in association with inactive or active corneal involvement, particularly stromal keratitis. It has been pointed out that iridocyclitis in an eye with a known history of herpetic keratitis should be considered herpetic until proved otherwise by the clinical findings or laboratory testing.

However, there is no direct correlation between herpetic keratitis and uveitis, which can occur in the absence of any corneal lesions.35

Figures 7A and B: A 32-year-old man presented with unilateral photophobia, blurred vision, pain and redness in his right eye for one week. Past history was significant for the presence of flu like illness, chills, malaise, joint pain and intermittent skin rashes two months before the onset of ocular problem.

(A) Systemic examination revealed disseminated symmetric papular lesions all over the body. The lesions were also seen in both palms and soles. (B) Ocular examination of the right eye revealed a large vascularised iris nodules located the papillary margin. Treponema pallidum haemagglutination test and FTA-ABS were positive. The patient was referred to primary physician for intravenous penicillin treatment

Ocular involvement is usually unilateral with patients suffering from blurred vision, photophobia, pain, and redness. On examination, one may find active keratitis or corneal scarring, and the corneal sensation can be depressed relative to the contralateral cornea. Anterior chamber cells and flare of varying degrees of severity, with or without posterior synechiae, are noted. Inflammation may be nongranulo-

Figures 8A and B: Acute granulomatous uveitis with pigmented central granulomatous corneal keratic precipitates (A and B, short arrows) and iris atrophic patches (B, long arrows) in a patient with herpetic anterior uveitis

matous or more often granulomatous with pigmented or non-pigmented keratic precipitates. Hypopion can very rarely be observed in severe forms, but hyphema is also possible. Focal areas of inflammation of the iris may be seen, and these may later evolve into transilluminating areas of iris atrophy (Figure 8). Increased intraocular pressure is also frequently observed and is a diagnostic element when present.

The diagnosis of herpetic anterior uveitis is usually based on the above mentioned clinical features. Laboratory tests on aspirates from the aqueous humor can help the clinician confirm the disease, especially in patients with atypical clinical presentation.35 Confirmation of intraocular viral infection with or without viral replication relies on molecular techniques