Download - Immunosuppressives in Ophthalmology
-
7/29/2019 Immunosuppressives in Ophthalmology
1/24
IMMUNOSUPPRESSIVES IN
OPHTHALMOLOGY
DR.SHWETA
-
7/29/2019 Immunosuppressives in Ophthalmology
2/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
3/24
Pre requisites of starting immunosuppressive
therapy
Informed consent should be obtained
Systemic work up:
Complete haemogram
Urinalysis
Liver function test
Renal function test
electrolytes
-
7/29/2019 Immunosuppressives in Ophthalmology
4/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
5/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
6/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
7/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
8/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
9/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
10/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
11/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
12/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
13/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
14/24
Contraindications:
Pts with H/O hypersensitivity to the drug
Immunosuppressed
Pregnant and nursing women
Pts of rheumatiod arthritis previously treated
with alkylating agents
-
7/29/2019 Immunosuppressives in Ophthalmology
15/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
16/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
17/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
18/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
19/24
Contraindications :
Hypersensitivity
Chronic liver disease
Pregnant and nursing women
Immunocompromised states
Pre existing bllod dyscrasias or bone marrow
suppression
-
7/29/2019 Immunosuppressives in Ophthalmology
20/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
21/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
22/24
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
-
7/29/2019 Immunosuppressives in Ophthalmology
23/24
-
7/29/2019 Immunosuppressives in Ophthalmology
24/24