1.Dr. Sunita Kumawat DEPTT. Of Ophthalmology SPMC Bikaner IMMUNOMODULATORS in OPHTHALMOLOGY

2. As the name implies, immunomodulators weaken or modulate the activity of the immune system. That in turn,decreases the inflammatory response. Immunomodulators are most often used in organ transplantation to prevent rejection of the new organ as well as in autoimmune diseases which appears to be caused by an overactive immune system 3. class Type of agent Name of agent corticosteroids Alkylating agent Nitrogen mustard cyclophosphamide chlorambucil Antimetabolite Folic acid analogs methotrexate Pyrimidine analogs 5-fluorouracil Purine analogs Azathioprine Natural products Antibiotics Cyclosporine Dapsone Tacrolimus Mitomycin Antibodies Antilymphocyte serum AntiT cell antibody Gamma globulin 4. Alkylating agents: Cyclophosphamide : most potent therapeutic alkylating agent. Converted to active metabolite(aldophosphamide & 4- hydroxycyclophosphamide) by liver. These active metabolite form DNA crosslinks between and within the DNA strands,leads to cell death,which acounts for their predominant immunosupressive activity. 5. Uses: 1. Cyclophosphamide is the treatment of choice for any patient with ocular manifestations of wegners granulomatosis or polyarteritis nodosa. 2. It can be used in Highly destructive form of inflammation in association with rheumatoid arthritis. 3. Necrotizing scleritis associated with relapsing polychondritis. 6. 4.Retinal vasculitis associated with sarcoidosis; 5.Pars planitis associated with multiple sclerosis; 6. Severe uveitis associated with ankylosing spondylitis, with Reiters syndrome, or with inflammatory bowel disease; 7. Idiopathic uveitis; and bilateral Moorensulcer, cicatricial pemphigoid. 7. 8.multifocal choroiditis associated with progressive systemic sclerosis; 9.Other OID including posterior uveitis or retinal vasculitis manifestations of Behets disease,juvenile idiopathic arthritis, sympathetic ophthalmia;Vogt-Koyanagi- Harada syndrome; birdshot retinochoroidopathy; multifocal choroiditis with panuveitis; retinal vasculitis associated with systemic lupus erythematosus. 8. Route : orally, IV For controlling ocular inflammation orally is more effective then intermittent IV pulses. DOSE : 2 mg/kg/day orally 9. Side effects: Potential complications of cyclophosphamide therapy includes: Severe bone marrow depression with resultant anemia, leukopenia,thrombocytopenia. Secondary infections. Anorexia, nausea, vomiting, hemorrhagic colitis, and oral mucosal ulceration;jaundice; hemorrhagic cystitis. Gonadal suppression,alopecia; and interstitial pulmonary fibrosis. 10. Chlorambucil: It interfere with DNA replication and prevent cellular division of rapidly proliferating cells, such as inflammatory and neoplastic cells. Used in retinal vasculitis in Behcets ds. side effects are same as cyclophosphamide.(except haemmorhagic cystitis which is a peculiar s/e of cyclophosphamide and it is not associated with chlorambucil). DOSE : 0.1 -0.2 mg/kg single daily dose orally. 11. Monitoring : Careful hematologic monitoring is must for use of alkylating agents Avoid depressing: WBC