Medical Care
The appropriate level of treatment is determined by the severity of the inflammation. Conflicting reports exist regarding the efficacy of steroids. Some patients with mild inflammation may respond well to regional injection of steroids. Other patients require the use of systemic prednisone for control of the inflammation. Some patients may be controlled for a while on less than 10 mg/d, while other patients require higher doses. Long-term treatment, even 10 mg/d of steroids, is undesirable, considering the high risk of significant morbidity and mortality of such treatment. Many patients show no significant response to steroid therapy. [1]
In addition, it is now very well documented that long-term outcomes of visual function are not altered with corticosteroid therapy.
Cyclosporine has been shown to have a beneficial effect on birdshot chorioretinopathy inflammation in retrospective case series. [14] Initial reports demonstrated improved visual acuity, decreased vitritis, and stabilization of eyes with cyclosporine dosages of 10 mg/kg/d. However, this dose also was associated with a high incidence of nephrotoxicity and hypertension. Vitale and colleagues reported a series of 19 cases of birdshot chorioretinopathy, which demonstrated that cyclosporine treatment with lower dosages, from 2.5-5 mg/kg, can be effective. [15] This series showed control of vitreal inflammation in 88.5% of eyes and improved or stable visual acuity in 83.3% of eyes. However, the low incidence of drug toxicity was most striking; there were only 2 cases of hypertension and no cases of nephrotoxicity.
Adalimumab therapy has been found effective in improving visual acuity in patients with refractory birdshot chorioretinopathy, although complete remission is rare. [16]
One suggestion is to initially start cyclosporine dosages at 2.5 mg/kg and then to increase to the level necessary to control the inflammation, while ensuring avoidance of drug adverse effects. The maximum dosage is 5 mg/kg according to this author. Monitoring for blood counts and renal function is performed every 4-6 weeks, along with blood pressure monitoring. Cyclosporine serum levels are not followed at these dosing regimens. Other potential adverse effects, such as hirsutism, paresthesias, tremor, and gingival hyperplasia, are not risks for morbidity, but are mentioned, since lowering of drug dosage or discontinuation of the medication may be indicated if such adverse effects occur to a point of affecting the quality of the patient's life.
One study reports the use of ketoconazole as adjunct therapy to cyclosporine. Ketoconazole delays metabolism of cyclosporine; hence, it may lower the dose of cyclosporine required to maintain control of inflammation. Silverstein and Wong demonstrated that cyclosporine trough levels could be maintained in a patient when the cyclosporine dosage was dropped from 200 mg/d (3 mg/kg) to 50 mg/d (0.75 mg/kg) with the addition of ketoconazole at 200 mg/d. This amounts to an 80% reduction of cyclosporine consumption. While this may be cost-saving, one cannot necessarily equate stabilization of cyclosporine serum levels with adequate control of inflammation nor with reduced potential toxicity. After all, the serum cyclosporine levels are still in the therapeutic range, and one might expect cyclosporine toxicity prevalence to be unchanged. Additionally, ketoconazole is not without potential adverse effects, especially the risk of hepatitis.
Other immunomodulatory therapies have been described. Kiss and colleagues reported the use of mycophenolate mofetil, azathioprine, methotrexate, and daclizumab in a series of 28 patients with birdshot chorioretinopathy; however, the small size of the study precludes any comment on the efficacy of any single drug. [17, 18, 14] LeHoang and colleagues reported the use of intravenous immunoglobulin in a series of 18 patients as initial therapy for active birdshot chorioretinopathy, and they noted stable vision in 33 of 36 eyes over a mean follow-up period of 39 months. [19] Daclizumab was withdrawn from the United States market because of diminished use and emergence of other effective therapies.
Long-Term Monitoring
Patients should be observed every 4-6 weeks. The patient is queried about visual quality, including color perception and vision at nighttime, and about symptoms of the potential adverse effects from the medications. The patient is examined, and blood tests and blood pressure measurement are performed. If the patient describes change in the quality of vision, despite a change in the visual acuity or evidence of active inflammation by examination, fluorescein angiography and indocyanine green angiography are performed to detect inflammation not seen readily on funduscopy, looking in particular for disk leakage or leakage from vessels. The use of serial ERGs as a tool to detect subclinical inflammation is being investigated.
This author believes in a zero tolerance for even minimal inflammation. When inflammation is not controlled, the dosage of the medication is increased; this is continued until the inflammation is controlled, the patient reaches the maximal tolerated dose, or the patient shows signs of drug toxicity. Although most cases can be controlled with this strategy, a small number of patients will have persistent inflammation despite regional steroids and maximally tolerated cyclosporine therapy. In these cases, combination immunosuppressive therapy may be indicated and will require management by a physician experienced in their use.
