A Phase I Study to Evaluate the Ocular and Non Ocular Safety of Ranibizumab in Treating Neovascularization Secondary to Sickle Cell Retinopathy

In the U.S., about 10% of African Americans have an abnormal hemoglobin gene. About 8% of African Americans are heterozygous for Hemoglobin S. In the United States, sickle cell anemia primarily occurs in the black population, with approximately 0.2% of African American children afflicted by this disease. It may be associated with other hemoglobinopathies as well. The prevalence in adults is lower because of the decrease in life expectancy. Systemically, the sickle cell anemia variation (SS) produces the most symptoms. With respect to the eye, the sickle cell disease mutation (SC) produces the most effects. Overall, the sickle cell trait expression (AS) produces the fewest complications.

• Among patients with SC or SThal, the incidence of proliferation sickle cell retinopathy is 33% and 14% respectively.
• Proliferative sickle cell retinopathy is the major cause of vision loss in sickle cell disease.

For sickle cell retinopathy, the commonly used therapeutic modalities include laser retinal photocoagulation, retinal cryotherapy, and vitrectomy/membranectomy depending on the severity of the disease. The most effective therapeutic modality with minimal postoperative complications appears to be scatter laser retinal photocoagulation.

A single case study of bevacizumab was found to effective in short term regression of neovascularization and improving vision after a single injection. Further study with ranibizumab is warranted.

Recent clinical trials (Marina and Anchor) have demonstrated that ranibizumab is effective in treating patients with CNV with age-related macular degeneration. Retinopathy in sickle cell disease has also been linked to VEGF. Therefore, patients with sickle cell retinopathy should respond to ranibizumab therapy.