Drugs used in Uveitis Capt Md Ferdous Islam

Trainee in OphthalmologyCMH ,Dhaka

Introduction

• The purpose is to describe the different drugs used in the treatment of uveitis. The term drug would incl eye drops, tablets and injections.

• It may be useful to remember the aims of treatment in uveitis:

What Should Treatment Achieve?• Relieve pain and discomfort.• Prevent sight loss due to the disease or its

complications.• Treat the cause of the disease where possible,

that is, treat the inflammation.• In a few types , the inflammation is caused by

an infection and treated with antibiotics or antiviral drugs.

• The drugs fall into 3 main groups: Steroids, Immunosuppressants and Mydriatics

Cycloplegics Mydriatics

• These ophthalmic preparations block the responses of the iris sphincter and the accommodative muscle of the ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia)

• Tropicamide 1%, cyclopentolate and atropine have both properties

• Phenylephrine has only mydriasis.

CycloplegicsPurpose:•To break or prevent posterior synechiae and to relieve ciliary spasm induced photophobia.•Dosing depends on the extent of inflammation

Posterior synechiae

CorticosteroidsMainstay of initial therapy

Topical Steroids

Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8

Topical Steroids

Injections

Adverse Effects of Corticosteroids

Cont.

Cont.

NSAIDS

Systemic NSAIDSComplications of prolonged use:• Myocardial infarction• Hypertension• Stroke (selective cox-2 inhibitors) • PUD• GI bleeding• Nephrotoxicity• Hepatotoxicity

Immunomodulatory Medications (IMT)

• Antimetabolites• T Cell Signaling Inhibitors• Alkylating Agents• Biologic Response Modifiers

Indications For IMTInadequate response of uveitis to corticosteroid therapy for

greater than 3 months with doses exceeding 5-10mg/day.Vision threatening Intraocular inflammation.Reversibility of disease process.Contraindications to corticosteroid use: 1. diabetes, hypertension, peptic ulcer, GERD,

immunocompromised state, psychiatric conditions2. exacerbated side effects3. chronic corticosteroid dependence

Precautions

No infection presentNo hepatic or hematologic contraindicationsClose physician follow upTeratogenicInformed Consent

Antimetabolites• Azathioprine, methotrexate, mycophenolate mofetil• Azathioprine (purine nucleoside analogue)-interferes with DNA replication and RNA transcription-found beneficial in VKHsyndrome, int. uveitis, Behcet uveitis,

sympathetic opthalmia and necrotizing scleritis-GI side effects (nausea, upset stomach) are cause for D/C.-CBC, LFT every 4-6 weeks.

Methotrexate• Folic Acid analogue• Inhibitor of dihydrofolate reductase and it’s DNA replication• Causes extracellular accumulation of adenosine to create an

anti-inflammatory effect.• Useful for iridocyclitis (first line choice IMT treatment for

children), sarcoidosis, panuveitis, various other types of uveitis

• Prospective study for IV inj. for refractory uveitis and uveitic CME.

Mycophenolate Mofetil

• Inhibits inosine monophosphate dehydrogenase and DNA replication

• Side effects: reversible GI distress, diarrhea• CBC monthly• 85% effectivity in chronic uveitis patients and a good

second choice IMT for children.

CYCLOSPORINE and TACROLIMUS• Calcineurin inhibitors- disrupt T-cell

receptor signal transduction and down regulate IL-2 transcription and CD4 T lymphocyte receptor expression.

SIROLIMUS• Non-calcineurin inhibitor- disrupts T cell

signaling that inhibits Ab production and B-lymphocytes.

T Cell Signaling Inhibitors

Cyclosporine

• SE: Nephrotoxicity and systemic hypertension; paresthesia, hypertrichosis.

• BP, CBC, s creatinine monthly.• Used for int. uveitis and posterior uveitis cases from

Behcets and VKH.• Used in combination with corticosteroids

Tacrolimus

• Low dose and increased potency to cyclosporine• Less risk of hypertension and hyperlipidemia• Useful for chronic int. and posterior uveitis.• Nephrotoxicity

Sirolimus

• One open-label, prospective study it was found useful in treatment for refractory noninfectious uveitis

• GI side effects• Under active investigation for use in treating uveitis

Alkylating AgentsCYCLOPHOSPHAMIDE• Active metabolites alkylate purines in DNA and RNA, creating

impaired DNA replication and cell death• Cytotoxic to dividing and resting lymphocytes• myelosuppression, hemorrhagic cystitis, sterilityCHLORAMBUCIL• Interferes with DNA replication• myelosuppression, sterilityTreatment for int. uveitis, VKH, SO, Behcet Increased risk for malignancy (leukemia, various cancers)

Biologic Response Modifiers{inhibitors of cytokines}

INFLIXIMAB• Chimeric, monoclonal IgG1k antibody against TNF alpha• Treatment for Behcet, sarcoidosis and VKH. Some HLA B27

ant. Uveitis • Drug induced toxicity (lupus, systemic vascular thrombosis,

CHF, malignancy, demyelinating disease and vitreous hemorrhage)

ADALIMUMAB• less AE, same effectiveness

Alternative Therapy Under FDA Investigation

• RITUXIMAB chimeric monoclonal antibody against CD20 positive cells (B lymphocytes)

• DACLIZUMAB monoclonal Ab to IL-2• IFN alpha 2a: antiviral, immunomodulatory and

antiangiogenic effects (leukopenia and thrombocytopenia,depression)