1. OCULAR MANIFESTATIONS OF SARCOIDOSIS
Dr.Rajesh Babu B
MS, FMRF, MSc (CEH) , DLSHTM, UK
Consultant
Uveitis & Ocular Immunology
Ocular Epidemiology & Community Eye Health
Narayana Nethralaya , Bangalore

2. Ocular Sarcoidosis Definition Epidemiology Theories of pathogenesis
Clinical manifestations
Symptoms
Complications
Pathology
Differential diagnosis
Investigations
Treatment
Prognosis

3. Definition
Sarcoidosis is a chronic multisystemic granulomatous disorder of unknown etiology thought to result from an exaggerated cellular immune response to a variety of self antigens or non-self antigens that is characterized by its pathological hallmark, the noncaseating granuloma.

4. The illness can be self-limited or chronic Episodic recrudescence and remissions.
Because the lungs and thoracic lymph nodes are almost always involved, most patients report acute or insidious respiratory problems, variably accompanied by symptoms affecting the skin, eyes, or other organs.

5. Epidemiology Sarcoidosis occurs worldwide.
Affecting persons of all races, both sexes, and all ages.
It has a particular proclivity for adults < age of 40 and for certain ethnic and racial groups (US blacks, Scandinavian and Irish white people).
The lifetime risk of sarcoidosis for U.S. blacks is 2.4 percent, and that for U.S. whites 0.85 percent.

6. Epidemiology
The frequency of sarcoidosis is reported to be low in various parts of the world.
It is not known whether this low frequency of sarcoidosis is genuine or whether it represents an underdiagnosis owing to the frequent occurrence of subclinical course, similarity with other diseases, or absence of firm diagnostic criteria.

7. Etiopathogenesis Mycobacterium remain leading suspects.
The cause of sarcoidosis remains obscure for a number of reasons
The heterogeneity of the manifestations of the disease
The lack of a precise definition
Clinical overlap with other disorders
and insensitive and nonspecific diagnostic tests that lead to misclassification of the disease .
Mycobacterium remain leading suspects.
Transmission after cardiac /bone-marrow transplant has been reported
Almenoff PL, Johnson A, Lesser M, Mattman LH. Growth of acid fast L forms from the blood of patients with sarcoidosis. Thorax 1996;51:
Burke WMJ, Keogh A, Maloney PJ, Delprado W, Bryant DH, Spratt P. Transmission of sarcoidosis via cardiac transplantation. Lancet 1990;336:
Heyll A, Meckenstock G, Aul C, et al. Possible transmission of sarcoidosis via allogeneic bone marrow transplantation. Bone Marrow Transplant 1994;14:

8. Theories of pathogenesis
The diverse manifestations of this disorder help fuel the prevailing hypothesis that sarcoidosis has more than one cause, each of which
may promote a different pattern of illness.

9. Theories of pathogenesis
Conceptually, it appears likely that
Genetically predisposed hosts are exposed to antigens that trigger an exaggerated cellular immune response and the formation of granulomas.

10. PATHOLOGICAL AND IMMUNOLOGIC FEATURES
Non-caseating granuloma holds the key to the diagnosis of sarcoidosis and provides clues to the immunopathogenesis of the disease.

11. Clinical Manifestations
Can be widespread or may involve only one organ system at a time.
Two peaks of incidence - the first at ages 20–30 years and the second at ages 50–60 years.
Ocular involvement manifests in 25%–60% of patients with systemic sarcoidosis.
Albert DM, Jakobiec FAHunter DG, Foster CS(1994) Ocular manifestations of sarcoidosis. in Principles and practice of ophthalmology . eds Albert DM, Jakobiec FA(WB Saunders, Philadelphia), pp 443–450.

12. Symptoms
The majority of patients, however, present with systemic symptoms such as fatigue, anorexia, weight loss, and fever .
Many report dyspnea on exertion, retrosternal chest pain, and cough .
This may precede of come many months and years later.
Ocular symptoms related to chronic granulomatous uveitis
Lid nodules, conjunctival injection and nodules, rarely proptosis

13. Symptoms
In 20 to 50 percent of the patients with more acute presentations, one sees the constellation of
Erythema Nodosum
Bilateral hilar lymphadenopathy
Polyarthralgias, known as Löfgren's syndrome.
Parotid involvement with uveitis is called Herfordt syndrome.

14. Examination findings
Ophthalmic lesions develop in approximately 25 percent of patients.
The classic symptom of anterior uveitis has a rapid onset, with blurred vision, photophobia, and excessive lacrimation; it usually clears spontaneously within a year.
Conjunctival involvement with small, pale, yellow nodules is common.

15. The most common ocular manifestations are uveitis (30%–70%) and conjunctival nodules (40%)
More than 80% of uveitis cases manifested before or within 1 year after the onset of systemic disease.

16. DIFFUSE MUTTON FAT KERATIC PRECIPITATES
AQUEOUS FLARE ++
AQUEOUS CELLS ++
FIBRIN PRESENT
IRIS NODULES
LENS CLEAR
NO VITREOUS REACTION
RIGHT EYE

17. Multiple koeppe’s and bussaca nodules

18. Conjunctival involvement has been reported in 6
Conjunctival involvement has been reported in % of patients with ocular sarcoidosis
Sarcoidosis granulomas are described as solitary, yellow "millet-seed" nodules.
CONJUNCTIVAL NODULES

19. Posterior segment manifestations
Intermediate Uveitis

20. Posterior segment manifestations
Disc edema
Active sarcoid granulomas

21. Complications
The clinical impact of sarcoidosis is directly related to the extent of granulomatous inflammation and its effect on the function of vital organs.
Specimens should be obtained from the most readily accessible organ with the least invasive method.

22. Complications
The clinical impact of sarcoidosis is directly related to the extent of granulomatous inflammation and its effect on the function of vital organs.
Specimens should be obtained from the most readily accessible organ with the least invasive method.

23. Pathology Small focus of necrosis.
The most common appearance of necrosis in sarcoidosis

24. Rather like a rugby scrum with all the players grouped around the ball; only with sarcoidosis the ball is invisible.

25. Small focus of necrosis

26. Granulomas involving a bronchiole

27. Angiotensin converting enzyme (ACE)
ACE is normally present in the vascular endothelium of many organs (lung, kidney, small intestine, uterus, prostate, thyroid, testes, adrenals) and in macrophages.
The macrophages accounts for elevated ACE levels in patients with sarcoidosis.
ACE is elevated in 60-90% of patients with active sarcoidosis.
A normal serum ACE does not exclude the diagnosis, especially if the disease is in its early stages, localized to a small area (e.g. the eye), and therefore with a small epithelioid cell "burden".

28. False low values of ACE Patients taking ACE inhibitors
Endothelial abnormalities, such as deep vein thrombosis
Patients who have had chemotherapy or radiation.
Treatment with systemic steroids or other immunosupressive agents can also affect ACE levels with values normalizing with adequate control of intraocular inflammation.

29. Elevated serum ACE Gaucher's disease Leprosy Chronic pulmonary disease
Rheumatoid arthritis
Spondylitis
Primary biliary cirrhosis
Tuberculosis
Histoplasmosis
Histiocytic medullary fibrosis
Hyperthyroidism
Diabetes mellitus.

30. Differential diagnosis
Any cause of chronic granulomatous diseases
Tuberculosis
Syphillis
Herpetic uveitis
Lymphoma
Metastases

31. Investigations
In the absence of a known causative agent, sarcoidosis remains a diagnosis of exclusion.
There are no definitive diagnostic blood, skin, or radiologic imaging tests specific for the disorder.
Even serum ACE and galluium 67 Scan s are not specific to Sarcoidosis
Gold standard is demonstration of non caseating granulomas from tissue .

32. Investigations CBC, ESR Mantoux test Chest X Ray Serum ACE levels
Lymph Node Biopsy
Broncheo Alveolar Lavage
Trans Bronchial Lung Biopsy
Other tests
TPHA
Sputum for AFB
Gallium 67 Scan

33. Gold standard
In most centers, skin and transbronchial lung biopsies have supplanted biopsy of mediastinal lymph nodes and the liver because of their high yield, greater specificity, and low morbidity.

34. Lungs and thoracic lymph nodes are affected in 90% of patients with sarcoidosis
Clinical staging is based on the pattern of chest radiographic findings:
Radiographic Staging of Pulmonary Sarcoidosis Using Conventional Chest Radiography

35. Stage 0--No abnormality is defined.

36. Bilateral hilar lymphadenopathy (BHL),stage 1

37. Stage 1- Hilar and paratracheal adenopathy without parenchymal involvement.
Bilateral hilar adenopathy is most common, followed by adenopathy in the right paratracheal area or aortopulmonary window area on the left.

38. BHL with parenchymal infiltrates, stage II

39. Bilateral hilar adenopathy with Mild interstitial disease in upper lobes.

40. Stage 2-Adenopathy with parenchymal involvement.
The parenchymal involvement includes a diffuse accentuation of interstitial markings resulting in a reticular pattern.

41. Sarcoidosis (with progression from stage II to stage III)

42. Parenchymal infiltrates, stage III

43. Signs of fibrosis with shrinkage, stage IV.

44. CT showing bilateral nodular infiltrates along bronchovascular bundles and enlarged mediastinal lymph nodes

45. Treatment
The optimal therapy for sarcoidosis is not well defined; therapeutic decisions are dictated by the localisation of the disease and severity of organ involvement.
The mainstay of treatment is corticosteroid therapy, which exhibits especially short term beneficial effects.

46. Treatment Steroid sparing drugs for longer term treatment
Methotrexate mg/week
Cyclosporin B 3-5 mg/kgBW/day
Azathioprine 1-3mg/kgBW BID/TID

47. Local Treatment Topical Prednisolone acetate eye drops
Peri-ocular Posterior subtenons triamcinolone acetonide
Dexamethasone implant in very severe recurrent cases

48. Prognosis
The poor visual prognosis was associated with the advanced age of the patients, black race, female sex, chronic systemic disease, and also with posterior segment involvement, peripheral punched out lesions, and the presence of cystoid macular oedema and glaucoma.
CME is leading cause of visual loss in sarcoid patients

49. Thank You