Vogt-Koyanagi-Harada (VKH) Disease Medication

Updated: Aug 17, 2018
  • Author: Fatma Zaguia, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Medication

Medication Summary

As previously mentioned, early, aggressive treatment with systemic corticosteroids—including prednisone and possibly, in the most severe cases, intravenous methylprednisolone—is key to the effective treatment of VKH disease (although intravenous therapy has not been found to improve visual outcomes).

Immunomodulatory treatment can be used in patients who are not responsive to high-dose systemic corticosteroids or who suffer from intolerable adverse effects. Immunomodulatory agents include cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, cyclophosphamide, and chlorambucil. [1, 69, 70, 71, 72, 73]

Infliximab is a chimeric immunoglobulin monoclonal antibody to tumor necrosis factor alpha. Infliximab has previously been shown to be effective in the treatment of uveitis. Several case reports have shown a promising role of infliximab in the treatment of VKH. [81]

Adalimumab, another biologic agent targeting TNF, was also reported to be effective in the treatment of VKH disease. [82]

Rituximab, a human-murine chimeric monoclonal antibody against CD20, has been reported to be effective in patients with VKH disease who did not respond to anti-TNF agents. [83]

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.

Prednisone

Prednisone is a synthetic adrenocortical steroid with predominantly glucocorticoid properties. An immunosuppressant, it is used for the treatment of autoimmune disorders. Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Prednisolone acetate (Millipred, Orapred, Pred Forte)

This agent is useful for the treatment of associated anterior uveitis. It decreases inflammation by suppressing the migration of PMN leukocytes and reversing increased capillary permeability.

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Cycloplegics

Class Summary

Instillation of a long-acting cycloplegic agent can relax any ciliary muscle spasm that is causing deep, aching pain and photophobia.

Homatropine (Isopto Homatropine), Cyclopentolate (Cyclogyl)

Homatropine and cyclopentolate block responses of the sphincter muscle of the iris and the muscle of the ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia). These agents induce mydriasis in 10-30 minutes and cycloplegia in 30-90 minutes. These effects last up to 48 hours. Individuals with heavily pigmented irides may require larger doses.

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Immunosuppressants

Class Summary

Agents in this category inhibit key factors involved in the immune response. May be used when inflammation is not controlled adequately by systemic corticosteroids and/or in patients who develop intolerable adverse effects. Ophthalmologists should seek the assistance of a clinician experienced in the use of these drugs when treating patients with ocular inflammatory diseases.

Cyclosporine (Sandimmune, Neoral, Gengraf)

Cyclosporine is a cyclic polypeptide that suppresses humoral immunity and, to a greater extent, cell-mediated immunity.

Mycophenolic Acid (Myfortic), Mycophenolate Mofetil (CellCept)

Myfortic is an enteric-coated formulation that delivers the active moiety mycophenolic acid (MPA). MPA is the same active moiety delivered by the prodrug mycophenolate mofetil (CellCept), which is combined to the mofetil moiety to improve the agent's oral bio­availability.

MPA inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production.

Azathioprine (Imuran)

Azathioprine may be used alone or as a steroid-sparing agent. It antagonizes purine metabolism and inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. Azathioprine may decrease the proliferation of immune cells, in this way lowering autoimmune activity.

Tacrolimus (Prograf)

Tacrolimus is a macrolide immunosuppressive agent that inhibits the activation of T cells.

Cyclophosphamide (Procytox, Endoxan)

Cyclophosphamide may be used as monotherapy or as a steroid-sparing agent. It is a cyclic polypeptide that is chemically related to nitrogen mustards and that suppresses some humoral activity. It is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

Cyclophosphamide is biotransformed by the cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. The interaction of phosphoramide mustard with DNA is considered to be cytotoxic.

When used in autoimmune diseases, cyclophosphamide's mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, the drug affects B cells by inhibiting clonal expansion and by suppressing the production of immunoglobulins. With long-term, low-dose therapy, cyclophosphamide affects T-cell functions.

Chlorambucil (Leukeran)

Chlorambucil is a bifunctional, slow-acting, aromatic nitrogen mustard derivative that interferes with DNA replication, transcription, and nucleic acid function by alkylation. Known chemically as 4-[bis(2chlorethyl)amino]benzene butanoic acid, the drug alkylates and cross-links strands of DNA.

Alkylation takes place through formation of the highly reactive ethylenimonium radical. Chlorambucil's probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.

Dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as an abrupt fall in the white blood cell count occurs.

Methotrexate (Trexall, Rheumatrex)

Methotrexate ameliorates the symptoms of inflammation (eg, pain, swelling, stiffness). Its mechanism of action in the treatment of inflammatory reactions is unknown, but immune function may be affected. Gradually adjust the dose to achieve a satisfactory response.

Infliximab

Infliximab is a chimeric immunoglobulin monoclonal antibody to tumor necrosis factor alpha. Infliximab has previously been shown to be effective in the treatment of uveitis. Several case reports have shown a promising role of infliximab in the treatment of VKH.

Adalimumab

Adalimumab, another biologic agent targeting TNF, was also reported to be effective in the treatment of VKH disease.

Rituximab

Rituximab, a human-murine chimeric monoclonal antibody against CD20, has been reported to be effective in patients with VKH disease who did not respond to anti-TNF agents.

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