Stewart, Michael W.

Background and Objective: Optical coherence tomography (OCT) was used to evaluate the macular thickness in eyes with advanced glaucoma compared with eyes following a retinal artery occlusion. Patients and Methods: Ten patients with a retinal artery occlusion and 10 patients with severe glaucoma were evaluated with OCT using the macular thickness map protocol. Results: The median thinnest macular sector was 183 microns (range: 152 to 223 microns) in patients with glaucoma versus 143 microns (range: 98 to 177 microns) in patients with arterial occlusion ( P = .001). Median macular volume was 5.9 mm 3 (range: 5.1 to 6.7 mm 3 ) in patients with glaucoma versus 5.1 mm 3 (range: 3.6 to 6.1 mm 3 ) in patients with arterial occlusion ( P = .015). Conclusions OCT demonstrates that patients with a retinal artery occlusion have significantly reduced macular thickness compared with those with severe glaucoma. [Ophthalmic Surg Lasers Imaging 2007;38:392–398.]

Background: Antibodies constitute an important drug development platform for drugs to treat several ophthalmic, oncologic, and immunologic conditions, but due to limitations inherent in antibody production and structure, a wide range of other protein binding scaffolds are being investigated. Designed ankyrin repeat proteins (DARPins) are simple to produce and offer a range of advantages over antibodies because of their stability, high binding affinity, and rigid structure. Objective: DARPins are being developed for a wide variety of medical applications, and the most studied molecule, abicipar pegol, is used to treat chorioretinal vascular diseases. This mini-review will discuss the current state of DARPin technology and will summarize drug development with a focus on abicipar. Methods: PubMed searches with keywords “DARPin” and “designed ankyrin repeat proteins” were performed and the reference lists of identified articles were examined for additional research material. Studies using DARPin molecules were identified at Clinicaltrials. gov. Non-peer reviewed data were found through Google searches of pertinent websites. Results: Abicipar prevents angiogenesis by binding all isoforms of vascular endothelial growth factor (VEGF)-A with single-digit picomolar affinity. Abicipar has a long intraocular half-life in rabbits and has produced promising results in pre-clinical studies. Pivotal phase III registration trials for the treatment of neovascular age-related macular degeneration are ongoing and a phase II/III trial for the treatment of diabetic macular edema has been announced. Conclusion: Abicipar pegol has the potential to effectively treat chorioretinal vascular conditions with an extended duration of action beyond those of currently used anti-VEGF drugs.

Background/Purpose: To describe the findings and clinical course of a patient with scleromyxedema complicated by retinal vasculitis and macular edema. Methods: Interventional case report. Results: A 64-year old Caucasian woman with recently diagnosed, biopsy proven scleromyxedema presented with decreased visual acuity (20/50 OD; 20/100 OS) due to retinal vasculitis and macular edema. She received intravitreal bevacizumab and subtenon's triamcinolone acetonide for the macular edema, and bilateral pars plana vitrectomies were required for vitreous hemorrhages. Monthly intravenous infusions of immunoglobulins (IVIG) resulted in resolution of the macular edema and vasculitis, and stabilization of the VA (20/40 OD; counting fingers at 6 feet OS). Conclusion: Scleromyxedema may be complicated by retinal vasculitis and macular edema. Treatment with corticosteroids and vascular endothelial growth factor inhibitors may be minimally effective but IVIG should be considered for both the ocular and systemic findings.

The treatment of exudative age-related macular degeneration (AMD) has been completely transformed by the development of drugs that bind vascular endothelial growth factor (VEGF). The antibody-based VEGF inhibitors bevacizumab and ranibizumab usually prevent the enlargement of choroidal neovascular membranes, reduce vascular permeability, and improve visual acuity. The newest VEGF inhibitor, aflibercept, is a soluble fusion protein that binds all isoforms of VEGF-A, VEGF-B, and placental growth factor with high affinity. Preclinical studies demonstrated aflibercept's ability to prevent experimental neovascularization and tumor growth in animal models. In phase 3 trials for exudative AMD, patients who received aflibercept avoided moderate vision loss and experienced improved visual acuity comparable to those who received ranibizumab. Additionally, patients who were treated with aflibercept 2 mg every 8 weeks (after 3 monthly loading doses) had similar visual results to those treated every 4 weeks. When treated as needed during the second year of the trials, patients were able to last an average of 3 months between aflibercept injections. Since its regulatory approval, aflibercept has also been found to perform well as a salvage therapy for eyes that respond incompletely to ranibizumab and bevacizumab. Because aflibercept can be administered less frequently than ranibizumab, it promises to decrease the frequency of patients’ visits to physicians’ offices in addition to the overall cost of AMD therapy.