immunosuppressives in ophthalmology

7/29/2019 Immunosuppressives in Ophthalmology

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IMMUNOSUPPRESSIVES IN

OPHTHALMOLOGY

DR.SHWETA


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ALKYLATING AGENTS:

Cyclophosphamide,chlorambucil

ANTIMETABOLITES:

Folic acid analogues: methotrexate

Pyrimidine analogues : 5 fluorouracil

Purine analogues : azathioprine

ANTIBIOTICS Cyclosporine,tacrolimus,mitomycin,dapsone

ANTIBODIES:

Antilymphocyte serum,anti T cellantibody,gamma globulin

Corticosteroids


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Pre requisites of starting immunosuppressive

therapy

Informed consent should be obtained

Systemic work up:

Complete haemogram

Urinalysis

Liver function test

Renal function test

electrolytes


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CORTICOSTEROIDS :

They are 21 carbon structures that are synthesized byACTH hormone controlled conversion of cholesterol in

adrenal cortex

They work at two levels : molecular and cellular

At molecular level they freely penetrate cellmembranes and bind to specific steroid binding proteinreceptor complex. This complex then enters thenucleus and binds to chromatin, signaling theproduction of messenger RNA and coding for enzymesand proteins that determine the response of that

particular cell to the hormone They affect lymphocyte proliferation by inhibiting

transcription factor signaling


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Indications:

Post operative control of inflammation

Immunosuppression

For diseases that have combined infectious andimmunocompromised process

Adverse effects:

Myopathy,osteoporosis,vertebral compression fractureof bone

Peptic ulcer,gastric haemorrhage,intestinal perforation Psychiatric disorders

Hyperglycaemia,hyperlipidaemia,centripetal obesity


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Hypertension Sodium and water retention

Lipodystrophy

Delayed wound healing

Menstrual irregularities,suppression of hypothalamo-pituitary-adrenal axis

Ocular:

Cataract Glaucoma

Mydriasis

Exophthalmos

Ptosis

Secondary infection

uveitis


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CYCLOPHOSPHAMIDE:

Nitrogen mustard family of alkylating agent

Inhibits B and T cell by causing DNA_DNA crosslinkage

Indications :

Peripheral ulcerative keratitis

Necrotizing scleritis

Bilateral Moorens ulcer

Behcets disease with posterior uveitis or retinal

vasculitis manifestationsActive,progressive ocular cicatricial pemphigoid


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Dose ; 1-3mg/kg

Dose is usually titrated to a target blood cellcount betn 3000-4000

Onset of action 6 weeks

Adverse effects :

Bone marrow suppression,affects WBCs more

than platelets.Leucopenia occurs by 1-2 weeksand recovery occurs by 2 weeks of stoppage ofdrug

Haemorrhagic cystitis

Gonadal dysfunction

Nausea,vomiting,anorexia and stomatitis

Reversible alopecia

Infections

Infertility


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Contraindications :

Patients with severly depressed bone marrow function

Patients with focal chorioretinitis

Herpes simplex and zoster

CMV,AIDS Retinopathy, toxoplasmosis,tuberculosis,fungal infections

Patients with previous hypersensitivity Treatment is stopped when

WBC count


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CHLORAMBUCIL

Slowest acting,least toxic and highly

carcinogenic

Inhibits Tand B cell proliferation by causing

DNA-DNA cross linkage

Indications :

Behcets disease

Uveitis recalcitrant to conventional therapy

Sympthetic ophthalmia

Intractable JRA associated iridocyclitis


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Dose : 0.1-0.2 mg/kg per day

Complications such as myelosuppression

increase significantly at doses greater than10mg/day

Onset of action 2-4 weeks

Adverse effects :

Myelosuppression

Sterility

Pulmonary fibrosis

seizures


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AZATHIOPRINE ;

Antimetabolite Purine analogue

Competitively inhibits purine synthesis,blocksDNA replication and RNA synthesis

Suppresses both T and B lymphcytes

Indications :Multifocal choroiditis with panuveitis

Behcets disease

Sympathetic ophthalmiaReiters associated iridocyclitis

VKH syndrome


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Sarcoidosis

Pars planitis

Steroid resistant forms of uveitis

JRA ass iridocyclitis unresponsive to conventionaltherapy

Dose ; 2-3 mg/kg per day

Adverse effects :Myelosuppression

Neoplasia(non-hodgkins lymphoma)

Nausea,vomiting

Hepatic veno-occlusive diseases

Pancreatitis


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Contraindications:

Pts with H/O hypersensitivity to the drug

Immunosuppressed

Pregnant and nursing women

Pts of rheumatiod arthritis previously treated

with alkylating agents


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CYCLOSPORINE:

It affects lymphocyte proliferation by inhibiting

transcription factor signaling which is required forproduction of potent T cell mitoge IL2

Indications :

Bilateral sight threatening uveitis of noninfectious etiology

Uveitis of various aetiology refractory to steroid

and cytotoxic agents

Sjogrens syndrome and atopic

keratoconjunctivitis sicca


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Dose : 2-5mg/kg per day

Adverse effects:

Nephrotoxicity

Systemic hypertension

Increased risk of Opportunistic infections

Hyperuricaemia and gouty arthritis

Contraindications : Hypersensitivity

Renal or hepatic insufficiency

Uncontrolled systemic hypertension

Pregnancy

Ocular :burning,conjunctival hyperaemia, discharge,pruritis,pain,epiphora,blurring,foreign body sensation


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METHOTREXATE:

Antimetabolite,folic acid antagonist

Prevents conversion of dihydrofolate totetrahydrofolate

Inhibits DNA replication and RNA transcription

Indications :

Steroid resistant cyclitis

Sympathetic ophthalmia resistant to conventionaltherapy

Paediatric uveitis refractory to conventionaltherapy

Scleritis ass with collagen vascular diseases


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Dose : 2.5-10mg orally,i.m,i.v in a 36-48 hr

period to a maximum of 50mg/week

Adverse effects:Myelosuppression

Pulmonary fibrosis

Hepatotoxicity

Ocular : irritation,photophobia,aggravation of

seborrheic blepharitis,epiphora


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Contraindications :

Hypersensitivity

Chronic liver disease

Pregnant and nursing women

Immunocompromised states

Pre existing bllod dyscrasias or bone marrow

suppression


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5-FLUOROURACIL

Antimetabolite,pyrimidine antagonist

Indication :Adjuvant in glaucoma surgery

Topical in basal cell carcinoma

Dose : 5-10mg subconjunctivallyintermediately after glaucoma surgery

Adverse effects

Bleb leakage,flat anterior chamber,blebitis,Superficial punctate keratopathy

Persistent epithelial defect


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MITOMYCIN C

Alkylating agent,acts by inhibiting DNA synthesis

Indication :Adjuvant in glaucoma surgery

Post operative in pterygium surgery

Dose : 0.4 mg/ml soaked in saturated cellulosesponge applied to scleral bed of trabeculectomywith conjunctiva draped over the sponge for 4min then vigorously irrigate the area with 45ml of

BSS after removal of sponge Single application 0.02% at the end of pterygium

surgery


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Adverse effects :

Conjunctival wound leaks

Corneal epithelial defects

Serious corneal infections in eyes with pre

existing corneal oedema

Corneal melting

Scleral ulceration

Calcification

Contraindiacation :

hypersensitivity


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immunosuppressives in ophthalmology

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