Part 3 • Medical Therapy and Surgical Intervention Chapter 7 Philosophy, Goals, and Approaches to Medical Therapy

helps in administration of ganciclovir at adequate dosages while antiretroviral therapy is continued. Long-term therapy, once available only through a central line placed to continue intravenous therapy, now includes a ganciclovir implant and oral anti-CMV medication. The introduction of sustainedrelease devices that deliver ganciclovir at a rate that provides therapeutic doses to the eye for up to 8 months has, in our experience, had a profoundly positive effect on the lifestyle of patients. Avoiding the need for daily infusions of drug has been important for these patients. There was of course a tradeoff: these patients were not being treated for the prevention of CMV infection elsewhere, such as in the contralateral eye. The use of oral ganciclovir (and other oral anti-CMV agents that may be developed) may be one alternative therapy that could be coupled with the local device.

Colchicine

Mode of Action

Colchicine, or acetyltrimethylcolchicinic acid, has poorly understood antiinflammatory characteristics. Colchicine suppresses lactic acid production in leukocytes and reduces phagocytosis. In addition, it also reduces polymorpho­ nuclear cell migration.

Indications and Dosages

Heightened polymorphonuclear cell migration is a characteristic of patients with Behçet’s disease (see Chapter 26) and may be a cause of the repeated ocular attacks seen in that disorder. Colchicine has been used in the treatment of Behçet’s disease. It should be stressed that this agent is not employed to treat the active inflammatory condition but rather is used prophylactically in the person with multiple ocular attacks to reduce the frequency of these attacks, which can lead to blindness. This approach has not met with universal approval, being more popular in Japan than in other countries with a high incidence of this disease, such as Turkey. Many believe that this agent is not effective in treating white patients. Its use might be considered in those fairly rare patients with Behçet’s disease who have unilateral involvement and in whom one may not feel fully justified in using more powerful immunosuppressive agents. The average dose of oral colchicine is 0.6 mg twice daily. Some clinicians have suggested that higher dosages may be helpful, but this is based on anecdotal information. Its effect on Behçet’s disease has been at best marginal in our experience.

Secondary Effects

Gastrointestinal reactions such as abdominal pain, diarrhea, nausea, and vomiting are quite common. Prolonged administration may cause bone marrow depression, with thrombocytopenia and aplastic anemia. Colchicine is contraindicated in pregnant women because it can harm the fetus.

Mydriatic and cycloplegic agents

The use of mydriatic and cycloplegic agents is an important adjunct to antiinflammatory or immunosuppressive therapy. The major indication for the use of dilating agents is the presence of a ‘significant’ anterior chamber inflammatory response. In those patients the addition of mydriatics helps

prevent the development of posterior synechiae and, in the extreme, iris bombe. Further, cycloplegia will make the patient more comfortable and helps ensure that the treating physician has an unhindered view of the media and fundus. We generally do not use long-term dilating agents, such as atropine, except postoperatively. Use of the shorter-acting agents, such as tropicamide (Mydriacyl), helps to keep the iris moving and hence reduces the possibility of posterior synechiae. One medication possibly to be avoided in patients with uveitis is cyclopentolate (Cyclogyl), as this has been shown to be an effective chemoattractant for leukocytes.279 Therefore, the addition of this medication to the therapeutic regimen may prove problematic.

Antitoxoplasmosis therapy

The therapeutic approach to treating ocular toxoplasmosis ideally consists of a combination of medications. Sulfadiazine (or trisulfapyrimidines, a mixture of sulfadiazine, sulfamerazine, and sulfamethazine) prevents the conversion of para-aminobenzoic acid to folic acid, which is needed for the carbon metabolism of the Toxoplasma organism, and in humans it is particularly needed for erythropoiesis (Fig. 7-23). Pyrimethamine (Daraprim) blocks the conversion of folic acid to folinic acid. A combination of these agents has been found to be synergistic in the killing of Toxoplasma. Sulfadiazine can be given as a 1–2 g loading dose, followed by 0.5–1 g orally four times daily. This is given in conjunction with a loading dose of 50–75 mg of pyrimethamine, followed by 25 mg twice daily. The therapy should be given for 3–4 weeks. Folic acid-containing vitamins should be stopped during this treatment period. Because of the potentially serious depression of erythropoiesis that can be a consequence of pyrimethamine therapy, leucovorin, 3–5 mg, is given orally or intramuscularly two or three times a week. We obtain a baseline white blood cell count with differential and a platelet count, and weekly thereafter. We give the leucovorin for 1 week after stopping the pyrimethamine. If there is a decrease in the platelet count (<100 000/mm3) or the appearance of hypersegmented polymorphonuclear lymphocytes, we discontinue the pyrimethamine. Pyrimethamine crosses the blood–brain barrier and is also used in the treatment of congenital toxoplasmosis. Sulfadiazine availability had been very limited in the United States, with clinicians needing to contact the Centers for Disease Control and Prevention in Atlanta, Georgia, for access. This situation has now been remedied, and the drug is now readily available.

Clindamycin has been shown to be effective in killing the Toxoplasma organism280 and has the added advantage of

Paraaminobenzoic Acid Dihydrofolate Exogenous folic acid

Sulfadiazine Pyrimethamine

Tetrahydrofolate

Integral role in

DNA metabolism

Figure 7-23.  Effects of sulfadiazine and pyrimethamine on carbon metabolism in Toxoplasma and in humans.