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

sensorimotor symptoms were detected in 50% of patients. It is postulated that many of the patients have mild or partial manifestations of the microangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar occlusions.109,110

BIRDSHOT CHORIORETINOPATHY

Birdshot chorioretinopathy is a noninfectious posterior uveitis with no known systemic involvement. The particularity of the disease consists in its parallel but independent involvement of the retina and the choroid. In the choroid the disease produces choroidal vasculitis and granulomatous infiltrations. Retinal vasculitis is prominent and involves large veins that show perivascular staining as well as capillaries that usually leak profusely producing extensive staining of the retina. Retinal exudation of the fluorescein dye can be such that there is never satisfactory marking of veins as the quantity of dye is never sufficient in concentration to produce sufficient fluorescence111 (Figure 20).

DIAGNOSTIC EVALUATION

The search for a cause in patients with retinal vasculitis often involves a multidisciplinary approach and laboratory investigation1,2 (Table 2). Discrimination between infectious or noninfectious aetiology of retinal vasculitis is important because treatment is different. Immunosuppressive therapy may be essential in certain disorders but it might be deleterious in infectious entities. Once an infectious cause is believed to be unlikely, an associated systemic disease should be considered and an appropriate investigation instituted. In cases of diagnostic doubt, malignancy must be ruled out and should certainly be considered if, after an initial improvement with therapy, the patient’s disease rapidly becomes refractory to treatment. The ophthalmologist, therefore, has a major role in clarifying the nosologic and diagnostic debate in patients with retinal vasculitis.

The laboratory work-up of a patient with retinal vasculitis should be based on a differential diagnosis derived from a detailed history, review of systems, and physical examination. If the patient’s medical history, review of systems, or ocular examination suggests an underlying systemic disease, then the diagnostic work-

Table 2: Diagnostic studies performed on patients with retinal vasculitis

A.Laboratory tests:

•Complete blood count with differential

•Erythrocyte sedimentation rate

•C-reactive protein

•Serum chemistry panel with tests for renal and liver functions

•Blood sugar

•Urinalysis

•Venereal Disease Research Laboratory (VDRL) test, Fluorescent treponemal antibody absorption (FTAABS) test

•Tuberculin skin testing

•Gamma interferon release assays for tuberculosis

•Toxoplasmosis serology

•Lyme disease serology

•Cat scratch disease serology

•Human immunodeficiency virus, human T cell lymphoma virus type 1, cytomegalovirus, herpes simplex virus, varicella zoster virus, hepatitis virus, and West Nile virus serology

•Polymerase chain reaction to identify pathogens in ocular specimens

•Serum angiotensin-converting enzyme

•Rheumatoid factor

•Antinuclear antibody

•Anti-dsDNA

•Antineutrophil cytoplasmic antibody

•Antiphospholipid antibodies (lupus anticoagulants and anticardiolipin antibodies)

•Serum complement, CH50, AH50

•Extractable nuclear antigen

•Serum protein electrophoresis

•Serum cryoglobulins

•Human leukocyte antigen testing

•Vitreous biopsy

•Cerebrospinal fluid cytology and cell count

B.Imaging

•Fluorescein angiography

•Optical coherence tomography

•Ultrasonography

•Chest X-ray

•CT scanning

•Magnetic resonance imaging

•Gallium scan

•Sacroiliac X-ray

The diagnostic work-up should be tailored according to the patient’s medical history, review of systems, and physical examination.

up should be tailored for that disease. The absence of any diagnostic clues from history makes idiopathic retinal vasculitis most likely. If, however, the patient has no signs or symptoms suggestive of an associated disease then the work-up of the patient is limited to a fluorescein angiogram, complete blood count, erythro-

cyte sedimentation rate, VDRL, FTA-ABS, blood chemistry, urinalysis, tuberculin skin testing, HIV serology, and chest radiograph. Numerous studies showed that little additional information is gained by “blind” investigation of the patient and that pursuing this is neither time nor cost effective.

Evaluation of patients with suspected infectious retinal vasculitis may include ocular and / or systemic cultures, serologic tests, polymerase chain reaction, and tuberculin skin testing. Tuberculin skin testing is often negative in sarcoidosis and in immunosuppressed individuals. In patients with suspected tuberculosis or Eales’ disease, chest radiograph and/or computed tomography of the chest may aid in the evaluation. Computed chest tomography was found to reveal the presence, dimensions, and activity of tuberculous mediastinal lymphadenopathy which routine chest X-rays were unable to detect in patients with presumed tuberculous retinal vasculitis(112).

In patients with suspected noninfectious systemic diseases, the diagnostic evaluation typically focuses on systemic vasculitis syndromes. Evaluation of these patients should include rheumatoid factor, antinuclear antibody, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigens, levels of complement, anticardiolipin antibodies, C-reactive protein, and imaging studies.

The study of human leukocyte antigen (HLA) testing may be helpful in certain forms of systemic disease associated with retinal vasculitis. These HLA associations include birdshot retinochoroidopathy and HLA-A29, Behçet’s disease and HLA-B51, and systemic lupus erythematosus and HLA-DR3.

If intraocular lymphoma is suspected, then vitreous biopsy is mandatory. Furthermore, because of the association between this disease and central nervous system lymphoma, a full neurological evaluation, including magnetic resonance imaging and cerebrospinal fluid cytological analysis is needed.

COMPLICATIONS AND PROGNOSIS

The causes of poor vision in retinal vasculitis are multifactorial, but cystoid macular oedema is a significant contributory factor. Cystoid macular oedema when adequately treated with immunosuppressive

therapy, is associated with a good prognosis.3 Poor visual outcome in some patients with retinal vasculitis despite adequate therapy may be explained by the presence of macular ischaemia on fluorescein angiography.113 Palmer et al3 demonstrated that patients with ischaemic retinal vasculitis have a significantly worse visual outcome than those with non-ischaemic retinal vasculitis. Inflammation induced vascular occlusion and ischaemia can lead to a proliferative vascular retinopathy, with sequelae such as recurrent vitreous haemorrhage, traction retinal detachment, rubeosis iridis, and neovascular glaucoma that can lead to functional loss of the eye.10,51,58,60,75,92,94,101 Recently, we demonstrated that aggressive treatment of Eales’ disease, an obliterative retinal periphlebitis, with systemic steroids and antituberculous therapy, full panretinal photocoagulation and early vitrectomy, when necessary, may result in improving the anatomic and visual outcome.10 Inflammatory branch retinal vein occlusions are strongly associated with Behçet’s disease and might contribute to visual loss.65,67,114 Retinal arterial occlusions are also reported in patients with retinal vasculitis.79,83,88,94,109,110

KEY POINTS

1.Retinal vasculitis may occur as an isolated idiopathic condition, as a complication of infective, or neoplastic disorders, or in association with systemic inflammatory disease.

2.Active vascular disease is characterised by sheathing or cuffing of blood vessels.

3.Fluorescein angiography demonstrates, leakage of dye, and staining of the blood vessel wall. It is also useful in confirming the presence of macular oedema, retinal vascular occlusion, and neovascularisation.

4.Optical coherence tomography is highly effective in the diagnosis of macular oedema and is the technique of choice for the follow-up and monitoring the effect of treatment.

5.Causes of poor vision are macular oedema, macular ischaemia, and proliferative vascular retinopathy, with sequelae such as recurrent vitreous haemorrhage, traction retinal detachment, rubeosis iridis, and neovascular glaucoma.

6.The search for a cause often involves a multidisciplinary team approach and laboratory investigation.

7.The laboratory work-up should be focused, based on a differential diagnosis derived from a detailed history, review of systems, and physical and ophthalmic examinations.

ACKNOWLEDGEMENT

The author thank Ms. Connie B. Unisa-Marfil for secretarial work.

REFERENCES

1.Herbort CP, Cimino L, Abu El-Asrar AM. Ocular vasculitis: a multidisciplinary approach. Curr Opin Rheumatol 2005;17:25-33.

2.Perez VL, Chavala SH, Ahmed M, et al. Ocular manifestations and concepts of systemic vasculitides. Surv Ophthalmol 2004;49:399-418.

3.Palmer HE, Stanford MR, Sanders MD, Graham EM. Visual outcome of patients with idiopathic ischaemic and non-ischaemic retinal vasculitis. Eye 1996;10:343-8.

4.Helm CJ, Holland GN. Ocular tuberculosis. Surv Ophthalmol 1993;38:229-56.

5.Rosen PH, Spalton DJ, Graham EM. Intraocular tuberculosis. Eye 1990;4:486-92.

6.Gupta A, Gupta V, Arora S, Dogra MR, Bambery R. PCRpositive tubercular retinal vasculitis. Clinical characteristics and management. Retina 2001;21:435-44.

7.Biswas J, Therese L, Madhavan HN. Use of polymerase chain reaction in detection of Mycobacterium tuberculosis complex DNA from vitreous samples of Eales’ disease. Br J Ophthalmol 1999;83:994.

8.Madhavan HN, Therese KL, Gunisha P, Jayanthi U, Biswas J. Polymerase chain reaction for detection of Mycobacterium tuberculosis in epiretinal membrane in Eales’ disease. Invest Ophthalmol Vis Sci 2000; 41:822-5.

9.Biswas J, Mukesh BN, Narain S, Roy S, Madhavan HN. Profiling of human leukocyte antigens in Eales’ disease. Int Ophthalmol 1998;21:277-81.

10.Abu El-Asrar AM, AL-Kharashi SA. Full panretinal photocoagulation and early vitrectomy improve prognosis of retinal vasculitis associated with tuberculoprotein hypersensitivity (Eales’ disease). Br J Ophthalmol 2002; 86:1248-51.

11.Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology 1990;97:1281-7.

12.Morgan CM, Webb RM, O’Connor GR. Atypical syphilitic chorioretinitis and vasculitis. Retina 1984;4:225-31.

13.Margo CE, Hamed AM. Ocular syphilis. Surv Ophthalmol 1992;37:203-20.

14.Gass JDM, Braunstein RA, Chenoweth RG. Acute syphilitic posterior placoid chorioretinitis. Ophthalmology 1990;97:1288-97.

15.Aldave AJ, King JA, Cunningham ET. Ocular syphilis. Curr Opin Ophthalmol 2001;12:433-41.

16.Browing D. Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis regimen of penicillin therapy, and the influence of human immunodeficiency virus status on response. Ophthalmology 2000; 107:2015-23.

17.Jumper JM, Machemer R, Gallemore RP, Jaffe GJ. Exudative retinal detachment and retinitis associated with acquired syphilitic uveitis. Retina 2000;20:190-4.

18.Theodossiodis P, Kokolakis S. Ladas I, Kollia AC, Chatzonlis D, Theodossiadis G. Retinal vascular involve-

ment in acute toxoplasmic retinochoroiditis. Int Ophthalmol 1995;19:19-24.

19.Ysasaga JE, Davis J. Frosted branch angiitis with ocular toxoplasmosis. Arch Ophthalmol 1999;117:1260-1.

20.Diaz-Valle D, Diaz-Rodriguez E, Diaz-Valle T, Benitez del Castillo JM, Toledano N, Fernandez Acenero MJ. Frosted branch angiitis and late peripheral retinochoroidal scar in a patient with acquired toxoplasmosis. Eur J Ophthalmol 2003;13:726-28.

21.Holland GN, Muccioli C, Silveira C, Weisz JM, Belfort R Jr, O’Connor GR. Intraocular inflammatory reactions without focal necrotizing retinochoroiditis in patients with acquired systemic toxoplasmosis. Am J Ophthalmol 1999; 128:413-20.

22.Sasaki K, Morooka I, Inomata H, Kashio N, Akamine T, Osame M. Retinal vasculitis in human T-lymphotropic virus type 1 associated myelopathy. Br J Ophthalmol 1989;73:812-5.

23.Nakao K, Ohba N. Clinical features of HTLV-1 associated uveitis. Br J Ophthalmol 1993;77:274-9.

24.Nakao K. Ohba N. HTLV-1 associated uveitis revisited: Characteristic grey-white, granular deposits on retinal vessels. Br J Ophthalmol 1996;80:719-22.

25.Nakao K, Ohba N. Human T-cell lymphotropic virus type 1-associated retinal vasculitis in children. Retina 2003; 23:197-201.

26.Levy-Clarke GA, Buggage RR, Shen D, Vaughen LO, Chan CC, Davis JL. Human T-cell lymphotropic virus-type 1 associated T-cell leukemia / lymphoma masquerading as necrotizing retinal vasculitis. Ophthalmology 2002; 109:1717-22.

27.Yoser SL, Forster DJ, Rao NA. Systemic viral infections and their retinal and choroidal manifestations. Surv Ophthalmol 1993;37:313-52.

28.Culbertson WW. Infections of the retina in AIDS. Int Ophthalmol Clin 1989;29:108-18.

29.Spaide RF, Vitale AT, Toth IR, Oliver JM. Frosted branch angiitis associated with cytomegalovirus retinitis. Am J Ophthalmol 1992;113:522-8.

30.Geier SA, Nasemann J, Klauss V, Kronawitter U, Goebel FD. Frosted branch angiitis in a patient with the acquired immunodeficiency syndrome. Am J Ophthalmol 1992;113:203-5.

31.Kestelyn P, Lepage P, Van de Perre P. Perivasculitis of the retinal vessels as an important sign in children with AIDSrelated complex. Am J Ophthalmol 1985;100:614-5.

32.Kestelyn P, Van de Perre P, Rouvroy D, et al. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome in Africa. Am J Ophthalmol 1985;100:230-8.

33.Fine HF, Smith JA, Murante BL, Nussenblatt RB, Robinson MR. Frosted branch angiitis in a child with HIV infection. Am J Ophthalmol 2001;131:394-6.

34.Ganatra JB, Chandler D, Santos C, Kuppermann B, Margolis TP. Viral causes of the acute retinal necrosis syndrome. Am J Ophthalmol 2000;129:166-72.

35.Tran TH, Stanescu D, Caspers-Velu L, et al. Clinical characteristics of acute HSV-2 retinal necrosis. Am J Ophthalmol 2004;137:872-9.

36.Holland GN, Executive Committee of the American Uveitis Society. Standard diagnostic criteria for the acute

retinal necrosis syndrome. Am J Ophthalmol 1994;117:663- 7.

37.Siam AL, Meegan JM, Gharbawi KF. Rift Valley fever ocular manifestations: Observations during the 1977 epidemic in Egypt. Br J Ophthalmol 1980;64:366-74.

38.Al-Hazmi A, Al-Rajhi AA, Abboud EB, et al. Ocular complications of Rift Valley fever outbreak in Saudi Arabia. Ophthalmology 2005;112:313-8.

39.Bains HS, Jampol LM, Caughron MC, Parnell JR. Vitritis and chorioretinitis in a patient with West Nile virus infection. Arch Ophthalmol 2003;121:205-7.

40.Anninger WV, Lomeo MD, Dingle J, Epstein AD, Lubow M. West Nile virus-associated optic neuritis and chorioretinitis. Am J Ophthalmol 2003;136:1183-5.

41.Hershberger VS, Augsburger JJ, Hutchins RK, Miller SA, Horwitz JA, Bergmann M. Chorioretinal lesions in nonfatal cases of West Nile virus infection. Ophthalmology 2003;110:1732-6.

42.Adelman RA, Membreno JH, Afshari NA, Stoessel KM. West Nile virus chorioretinitis. Retina 2003;23:100-01.

43.Vandenbelt S, Shaikh S, Capone A Jr, Williams GA. Multifocal choroiditis associated with West Nile virus encephalitis. Retina 2003;23:97-9.

44.Khairallah M, Ben Yahia S, Ladjimi A, et al. Chorioretinal involvement in patients with West Nile Virus infection. Ophthalmology 2004;111:2065-70.

45.Kaiser PK, Lee MS, Martin DA. Occlusive vasculitis in a patient with concomitant West Nile virus infection. Am J Ophthalmol 2003;136:928-30.

46.Chan CK, Limstrom SA, Tarasewicz DG, Lin SG. Ocular features of West Nile virus infection in North America: a study of 14 eyes. Ophthalmology 2006;113:1539-46.

47.Garg S, Jampol LM, Wilson JF, Batle IR, Buettner H. Ischemic and hemorrhagic retinal vasculitis associated with West Nile virus infection. Retina 2006;26:365-7.

48.Alio J, Ruiz-Beltran R, Herrero-Herrero JI, Hernandez E, Guinaldo V, Millan A. Retinal manifestations of mediterranean spotted fever. Ophthalmologica 1987;195:31-7.

49.Khairallah M, Ladjimi A, Chakroun M, et al. Posterior segment manifestations of Rickettsia Conorii infection. Ophthalmology 2004;111:529-34.

50.Lim JI, Tessler HH, Goodwin JA. Anterior granulomatous uveitis in patients with multiple sclerosis. Ophthalmology 1991;98:142-5.

51.Vine AK. Severe periphlebitis, peripheral retinal ischemia, and preretinal neovascularization in patients with multiple sclerosis. Am J Ophthalmol 1992;113:28-32.

52.Arnold AC, Usaf M, Pepose TS, Hepler RS, Foos RY. Retinal periphlebitis and retinitis in multiple sclerosis. I. pathologic characteristics. Ophthalmology 1984;91:255-62.

53.Graham EM, Francis DA, Sanders MD, Rudge P. Ocular inflammatory changes in established multiple sclerosis. J Neurol Neurosurg Psychiatry 1989;52:1360-3.

54.Engell T, Andersen PK. The frequency of periphlebitis retinae in multiple sclerosis. Acta Neurol Scand 1982;65: 601-8.

55.Birch MK, Barbosa S, Blumhardt LD, O’Brien C, Harding SP. Retinal venous sheathing and the blood-retinal barrier in multiple sclerosis. Arch Ophthalmol 1996;114:34-9.

56.Rucker CW. Sheathing of the retinal veins in multiple sclerosis; review of pertinent literature. Mayo Clin Proc 1972;47:335-40.

57.Prineas JW, Wright RG. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest 1978;38:409-21.

58.Morse PH.Retinal venous sheathing and neovascularization in disseminated sclerosis. Ann Ophthalmol 1975; 7:949-52.

59.Towler HM, Lightman S. Symptomatic intraocular inflammation in multiple sclerosis. Clin Experiment Ophthalmol 2000;28:97-102.

60.Valentincic NV, Kraut A, Rothova A. Vitreous hemorrhage in multiple sclerosis-associated uveitis. Ocul Immuno Inflamm 2007;15:19-25.

61.O’Halloran HS, Pearson PA, Lee WB, Susac JO, Berger JR. Microangiopathy of the brain, retina, and cochlea (Susac syndrome). A report of five cases and a review of the literature. Ophthalmology 1998;105:1038-44.

62.Do TH, Fisch C, Evoy F. Susac syndrome: report of four cases and review of the literature. AJNR Am J Neuroradiol 2004;25:38288.

63.Martinet N, Fardeau C, Adam R, et al. Fluorescein angiographies in Susac syndrome. Retina 2007;27:1238-42.

64.International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990;335:1078-80.

65.Sakane T, Takeno M. Novel approaches to Behçet’s disease. Exp Opin Invest Drugs 2000;9:1993-2005.

66.Verity DH, Wallace GR, Vaughan RW, Stanford MR. Behçet’s disease: from Hippocrates to the third millennium. Br J Ophthalmol 2003;87:1175-83.

67.Okada AA. Drug therapy in Behçet’s disease. Ocul Immunol Inflamm 2000;8:85-91.

68.Crick RP, Hoyle C, Smellie H. The eyes in sarcoidosis. Br J Ophthalmol 1961;45:461-81.

69.Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 1986;102:297-301.

70.Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 1978;86;648-55.

71.Rothova A. Ocular involvement in sarcoidosis. Br J Ophthalmol 2000; 84:110-6.

72.Nicholas J. Sarcoidosis. Curr Opin Ophthalmol 2002; 13:393-6.

73.Gold DH, Morris DA, Henkind P. Ocular findings in systemic lupus erythematosus. Br J Ophthalmol 1972;56: 800-4.

74.Lanham JG, Barrie T, Kohner EM, Hughes GRVO. SLE retinopathy: evaluation by fluorescein angiography. Ann Rheum Dis 1982;41:473-8.

75.Jabs DA, Fine SL, Hochberg MC, Newman SA, Heiner GG, Stevens MB. Severe retinal vaso-occlusive disease in systemic lupus erythematosus. Arch Ophthalmol 1986;104:55863.

76.Asherson RA, Merry P, Acheson JF, Harris EN, Hughes GRV. Antiphospholipid antibodies: A risk factor for occlusive ocular vascular disease in systemic lupus erythematosus and the primary antiphospholipid syndrome. Ann Rheum Dis 1989;48:358-61.

77.Quillen DA, Stathopoulos NA, Blankenship GW, Ferriss JA. Lupus associated frosted branch periphlebitis and exudative maculopathy. Retina 1997;17:449-51.

78.Karpik AG, Schwartz MM, Dickey LE, Streeten BW, Roberts JL. Ocular immune reactants in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 1985;35:295-312.

79.Abu El-Asrar AM, Naddaf HO, Al-Momen A, Al-Balla SR. Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion. Lupus 1995;4:158-60.

80.Bullen CL, Liesegang TJ, McDonald TJ, De Remee RA. Ocular complications of Wegener’s granulomatosis. Ophthalmology 1983;90:279-90.

81.Spalton DJ, Graham EM, Page NGR, Sanders MD. Ocular changes in limited forms of Wegener’s granulomatosis. Br J Ophthalmol 1981;65:553-63.

82.Pulido JS, Goeken JA, Nerad JA, Sobol WM, Folberg R. Ocular manifestations of patients with circulating antineutrophil cytoplasmic antibodies. Arch Ophthalmol 1990;108:845-50.

83.Iida T, Spaide RF, Kantor J. Retinal and choroidal arterial occlusion in Wegener’s granulomatosis. Am J Ophthalmol 2002;133:151-2.

84.Venkatesh P, Chawla R, Tewari HK. Hemiretinal vein occlusion in Wegener’s granulomatosis. Eur J Ophthalmol 2003;13:722-5.

85.Wang M, Khurana RN, Sada SR. Central retinal vein occlusion in Wegener’s granulomatosis without retinal vasculitis. Br J Ophthalmol 2006;90:1435-6.

86.Morgan CM, Foster CS, Gragoudas ES. Retinal vasculitis in polyarteritis nodosa. Retina 1986;6:205-9.

87.Akova YA, Jabbur NS, Foster CS. Ocular presentation of polyarteritis nodosa. Clinical course and management with steroid and cytotoxic therapy. Ophthalmology 1993; 100:1775-81.

88.Hsu CT, Kerrison JB, Miller NR, Goldberg MF. Choroidal infarction, ischemic optic neuropathy, and central retinal artery occlusion from polyarteritis nodosa. Retina 2001;21: 348-51.

89.Emad Y, Basaffar S, Ragab Y, Zeinhom F, Gheita T. A case of polyarteritis nodosa complicated by left central retinal artery occlusion, ischemic optic neuropathy, and retinal vasculitis. Clin Rheumatol 2007;26:814-6.

90.Curi ALL, Freeman G, Pavesio C. Aggressive retinal vasculitis in polyarteritis nodosa. Eye 2001;15:229-31.

91.Ruby AJ, Jampol LM. Crohn’s disease and retinal vascular disease. Am J Ophthalmol 1990;110:349-53.

92.Salmon JF, Ursell PG, Frith P. Neovascular glaucoma as a complication of retinal vasculitis in Crohn’s disease. Am J Ophthalmol 2000;130:528-30.

93.Sykes SO, Horton JC. Steroid-responsive retinal vasculitis with a frosted branch appearance in Crohn’s disease. Retina 1997;17:451-4.

94.Saatci OA, Koçak N, Durak I, Ergin MH. Unilateral retinal vasculitis, branch retinal artery occlusion and subsequent retinal neovascularization in Crohn’s disease. Int Ophthalmol 2002;24:89-92.

95.Ito Y, Nakano M, Kyu N, Takeuchi M. Frosted branch angiitis in a child. Jpn J Clin Ophthalmol 1976;30:797-803.

96.Kleiner RC, Kaplan HJ, Shakin JL, Yannuzzi LA, Crosswell HH Jr, McLean WC Jr. Acute frosted retinal periphlebitis. Am J Ophthalmol 1988;106:27-34.

97.Kleiner RC. Frosted branch angiitis: Clinical syndrome or clinical sign?. Retina 1997;17:370-1.

98.Markomichelakis NN, Barampouti F, Zafirakis P, Chalkiadakis I, Kouris T, Ekonomopoulos N. Retinal vasculitis with a frosted branch angiitis-like response due to herpes simplex virus type 2. Retina 1999;19:455-7.

99.Sugin SL, Henderly DE, Friedman SM, Jampol LM, Doyle JW. Unilateral frosted branch angiitis. Am J Ophthalmol

1991;111:682-5.

100.Borkowski LM, Jampol LM. Frosted branch angiitis complicated by retinal neovascularization. Retina 1999; 19:454-5.

101.Abu El-Asrar AM, Al-Obeidan SA, Abdel Gader AGM. Retinal periphlebitis resembling frosted branch angiitis with nonperfused central retinal vein occlusion. Eur J Ophthalmol 2003;13:807-812.

102.Kincaid J, Schatz H. Bilateral retinal arteritis with multiple aneurysmal dilatations. Retina 1983;3:171-8.

103.Chang TS, Aylward W, Davis JL, et al. Idiopathic retinal vasculitis, aneurysms, and neuro-retinitis. Ophthalmology 1995;102:1089-97.

104.Samuel MA, Equi RA, Chang TS, et al. Idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN): new observations and a proposed staging system. Ophthalmology 2007;114:1526-9.

105.Abu El-Asrar AM, Jestaneiah S, Al-Serhani AM. Regression of aneurysmal dilatations in a case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) associated with allergic fungal sinusitis. Eye 2004;18:197- 9.

106.Owens SL, Gregor ZJ. Vanishing retinal arterial aneurysms: a case report. Br J Ophthalmol 1992;76:637-8.

107.Sashihara H, Hayashi H, Oshima K. Regression of retinal arterial aneurysms in a case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN). Retina 1999; 19: 250-1.

108.Tomita M, Matsubara T, Yamada H, et al. Long term follow up in a case of successfully treated idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN). Br J Ophthalmol 2004;88:302-3.

109.Gass JDM, Tiedeman J, Thomas MA. Idiopathic recurrent branch retinal arterial occlusion. Ophthalmology 1986;93: 1148-57.

110.Johnson MW, Thomley ML, Huang SS, Gass JDM. Idiopathic recurrent branch retinal arterial occlusion. Natural history and laboratory evaluation. Ophthalmology 1994; 101:480-9

111.Herbort, CP, Probst K, Cimino L, Tran VT. Differential inflammatory involvement of retina and choroid in birdshot chorioretinopathy. Klin Monatsbl Augenheilk 2004; 221:351-6.

112.Metha S. Role of computed chest tomography (CT scan) in tuberculous retinal vasculitis. Ocul Immunol Inflamm 2002;10:151-5.

113.Bentley CR, Stanford MR, Shilling JS, Sanders MD, Graham EM. Macular ischaemia in posterior uveitis. Eye 1993;7:411-4.

114.Graham EM, Stanford MR, Sander MD, Kasp E, Dumonde DC. A point prevalence stgudy of 150 patients with idiopathic retinal vasculitis: I. Diagnostic value of ophthalmological features. Br J Ophthalmol 1989;73:714-21.

INTRODUCTION

Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology characterized by the presence of noncaseating granulomas in involved organs. It predominantly affects the lungs and intrathoracic lymph nodes, but any organ or system can be involved. Involvement of the eyes and adnexa occurs in 25–80% of sarcoidosis patients.1-4

The disease can involve the orbit, lacrimal gland, anterior and posterior segments. Sarcoidosis accounts for 1.7 to 7% of all uveitis cases,5-7 and symptomatic uveitis, typically granulomatous in nature, affects 20 to 30% of patients with sarcoidosis at some point.5

The diagnosis of sarcoidosis is based on laboratory findings and, if possible, confirmatory biopsy demonstrating noncaseating granuloma.

The eye disease may occur in the absence of apparent systemic involvement or may be the main site of disease without significant clinical disease elsewhere. Uveitis is reported to precede systemic sarcoid symptoms in about 30% of patients,8 and sarcoidosis diagnosis is particularly challenging in such case.

ETIOLOGY AND EPIDEMIOLOGY

The etiology of sarcoidosis is unknown, and it is assumed that systemic cellular immunity against exogenous infectious agents initiates the disease and causes the granuloma formation. The putative causative infectious agents of sarcoidosis include mycobacterium tuberculosis9, mumps10, and propionibacterium acnes11,12. Environmental exposure to

beryllium, aluminum, and zirconium also have been implicated in the pathogenesis of the disease.5, 13

Sarcoidosis has a worldwide distribution, with variable incidence among geographical regions. The exact prevalence and incidence are not known. Sarcoidosis is 3 to 4 times more common in US blacks than whites.14 The disease usually presents in adults between 20 and 40 years of age in both genders. A second peak occurs for women aged 45-65 years.15 It is currently the most common cause of uveitis in Japan.16 However, epidemiological survey of sarcoidosis in many different countries is difficult due to the lack of diagnostic criteria internationally accepted.

SYSTEMIC MANIFESTATIONS

Sarcoidosis generally presents with bilateral hilar lymphadenopathy (BHL), pulmonary infiltrates (Figure 1) and skin or eye lesions. Symptomatic patients with pulmonary sarcoidosis present with nonproductive cough, dyspnea, chest pain, fatigue, weakness, malaise, fever, and weight loss. In approximately one-half of the cases the disease is asymptomatic and incidentally detected by abnormalities on a routine chest X-ray.17

Extrapulmonary sarcoidosis can involve any organ or system. Skin lesions may be found in at least 15% of patients. They may be specific, showing noncaseating granulomas, or nonspecific (e.g., erythema nodosum).

The most common other locations are reticuloendothelial system, musculoskeletal system, exocrine glands, heart, kidney, and central nervous system (Table 1).

Figure 1: Chest X-ray study of a patient with uveitis showing bilateral hilar lymphadenopathy (BHL) and pulmonary infiltrates

The clinical course of sarcoidosis may be acute or chronic. Acute disease develops suddently and is characterized by constitutional symptoms such as fever, erythema nodosum, arthralgias, and parotid enlargement or uveitis. Acute disease may be severe, causing serious disability. It may resolve with minimal residual sequelae or may progress to chronic sarcoidosis. Chronic sarcoidosis develops insidiously over several months and is not associated with constitutional symptoms. There is often progressive pulmonary fibrosis and obstruction of the airways.

OCULAR MANIFESTATIONS

Ocular involvement occurs in 20 to 80% of patients with sarcoidosis at any time during the course of the

disease.18 It may develop in the absence of apparent systemic involvement or may be the main site of disease without significant clinical disease elsewhere. Any part of the eye or adnexa can be affected, with uveitis being the most common ocular manifestation (Table 2).

ADNEXAL INVOLVEMENT

Common manifestations of orbital sarcoidosis include palpable mass, proptosis, palpebral swelling, ptosis, diplopia, keratoconjunctiva sicca, exposure keratopathy, and myositis.19,20 A case of orbital sarcoidosis manifesting with enophthalmos has been recently reported.21

Lacrimal gland infiltration has been noted in up to 30% of patients with ocular sarcoidosis.22 It may remain asymptomatic, until tear production is severely compromised and patients complain of dry eye. It has been reported that lacrimal gland involvement is the most commonly affected orbital site (55-61%).20, 23 It is often bilateral and may be associated with parotid swelling and dacryoadenitis (Heerfordt syndrome).22 Conjunctival nodules have been reported in 6.9 to 70% of patients with ocular sarcoidosis.2,24 They may be seen on the fornix or palpebral conjunctiva in the form of yellowish slightly elevated lesions.

ANTERIOR SEGMENT DISEASE

Anterior segment involvement is observed in nearly 85% of patients with ocular sarcoidosis.25

Table 2: Ocular manifestations of sarcoidosis

Anterior Uveitis

Anterior uveitis is the most common ocular manifestation of sarcoidosis (85% of patients with ocular involvement). It is usually bilateral, chronic, and granulomatous, characterized by mutton fat or small keratic precipitates (Figures 2 and 3), iris nodules, and posterior synechiae. Iris nodules have been reported in up to 12.5% of patients with ocular sarcoidosis.2, 26 They may involve the pupillary margin (Koeppe nodules) (Figure 4) or the anterior stroma (Busacca nodules) (Figure 5). Nodules located on trabecular meshwork may also be noted. Tent-shaped peripheral anterior synechiae have also been described.

Acute anterior uveitis manifesting clinically with ciliary injection, aqueous cells, and flare, and some-

times fine keratic precipitates is noted in about 15% of patients with ocular sarcoidosis.25

Figure 3: Small granulomatous KPs and posterior synechiae

Figure 4:. Iris pupillary margin nodules (Koeppe Nodules)

Figure 2: Large granulomatous (mutton-fat ) keratic precipitates (KPs)

Figure 5: Iris stromal nodules (Busacca nodules)

Other Findings

Corneal changes have been reported, including limbal and corneal nodules, nummular-appearing keratitis, interstitial keratitis, and endothelial fibrosis.

Anterior scleritis is relatively rare; it can be diffuse or nodular. Scleral plaques have been reported in up to 2% of patients.2 Episcleritis can also occur.

POSTERIOR SEGMENT DISEASE

Posterior segment involvement is seen in 25% of patients with ocular sarcoidosis,22 and it can be the sole manifestation of the disease in 5% of patients.

Intermediate Uveitis

Intermediate uveitis has been reported in 16 to 38% of patients with posterior segment involvement.24,27 Clinical features include vitritis, string of pearls vitreous opacities (Figure 6), snowballs (Figure 7) , and snowbank.

Posterior Uveitis

Posterior uveitis occurrs in 12% of patients. It is usually chronic and more common in white women with late onset of the disease.27

The predominant posterior segment manifestations of sarcoidosis are chorioretinitis and retinal periphlebitis. The chorioretinal lesions are typically multifocal and located in the inferior peripheral fundus (Figure 8), and it is unusual for them to appear in the posterior pole. They characteristically appear as

Figure 6: String of pearls vitreous opacities

Figure 7: Snowballs

Figure 8: Multiple chorioretinal peripheral lesions

patches of creamy-yellow chorioretinal lesions, which are later, associated with overlying hypoor hyperpigmentation.

Retinal vasculitis, commonly presenting as segmental sheathing of veins (periphlebitis), occcurs in 9 to 34% of cases (Figure 9).2,22,24 The ophthalmoscopic appearance of “candle-wax drippings” in more severe cases is a hallmark of the disease (Figure 10). This finding, though not pathognomonic, suggests the diagnosis of sarcoidosis.

Cystoid macular edema has been reported in 19 to 72% of patients with posterior segment inflammation.24,27 Fluorescein angiography and optical coherence tomograhy are useful in the detection and evaluation of macular edema.

Figure 10: Nodular and/or segmental periphlebitis with canddle-wax drippings

Other Posterior Segment Findings

Other posterior segment manifestations of sarcoidosis include solitary choroidal granulomas,28 serpiginous choroiditis, birdshot-like chorioretinopathy,29 retinal vein occlusion, ischemic retinopathy, retinal or optic disc neovascularization,17,27 multiple arteriolar macroaneurysms,30 choroidal neovascularization, posterior scleritis, and exudative retinal detachment.31

NEURO-OPHTHALMOLOGIC MANIFESTATIONS

Optic nerve involvement can be observed in a substantial proportion of patients with ocular sarcoidosis.31 Granuloma of the optic nerve head may be

ROLE OF FLUORESCEIN ANGIOGRAPHY (FA) AND INDOCYANINE GREEN ANGIOGRAPHY (ICGA) IN OCULAR SARCOIDOSIS

FLUORESCEIN ANGIOGRAPHY (FA)

Fluorescein angiography (FA) is a useful tool for the diagnosis and follow-up of posterior segment involvement in sarcoidosis. It is especially useful in the evaluation of retinal vascular involvement. Although characteristic funduscopic findings in posterior segment include periphlebitis, this lesion is sometimes subclinical and only visible on FA in the form of focal or diffuse perivenous leakage in the affected areas (Figure 12).32 FA is necessary for the assessement of retinal capilliritis that may present as focal of diffuse retinal capillary leakage in the periphery or posterior pole. FA is useful in detecting and evaluating retinal