Alan D. Letson

RADIAL OPTIC NEUROTOMY FOR CENTRAL RETINAL VEIN OCCLUSION: A RETROSPECTIVE PILOT STUDY OF 11 CONSECUTIVE CASES

Purpose Retinal vascular occlusive disease is the second leading cause of permanent retinal blindness. The etiology of central retinal vein occlusion (CRVO) is not well understood. The anatomy of the optic disk including the cribriform plate and scleral ring may contribute to the development of retinal vaso-oclussive diseases. Neurovascular compression within the confined space at this location may play a pathoetiologic role in CRVO. The authors performed radial optic neurotomy in patients with CRVO to relax this space and relieve pressure on the central retinal vein. Methods Radial optic neurotomy (RON) was performed on 11 consecutive patients with severe, hemorrhagic CRVO with visual acuities of 20/400 or less. A microvitreoretinal blade was used to relax the scleral ring, cribriform plate, and adjacent sclera of the optic disk. Reperfusion of the retina was achieved via decompressing the central retinal vein. Results Radial optic neurotomy was performed successfully in all 11 patients. There were no complications noted with this procedure. All patients had clinical improvement as determined by fundus examination, photography, and fluorescein angiography. Postoperative visual acuities were equal or improved in 82% of patients. Eight of the patients (73%) had rapid improvement of visual acuity with an average gain of five lines of vision. Conclusions Surgical decompression of CRVO via RON is a technically feasible and initially safe procedure that is associated with rapid reperfusion of the retina. Resolution of the intraretinal hemorrhage, edema, and ischemia may improve the visual prognosis in patients with this common retinal disorder.

Chemotherapy for Treatment of Choroidal Metastases from Breast Carcinoma

Of 15 patients with choroidal metastases from breast carcinoma, eight were treated with radiation therapy and six with chemotherapy. One patient received both. Although five of the six patients receiving chemotherapy died after an average follow-up period of 12 months, these patients generally had more widespread disease and a worse prognosis originally. Chemotherapy proved to be as effective as radiation therapy for this tumor.

Multifunctional microbubbles for image-guided antivascular endothelial growth factor therapy.

We synthesize multifunctional microbubbles (MBs) for targeted delivery of antivascular endothelial growth factor (antiVEGF) therapy with multimodal imaging guidance. Poly-lactic-co-glycolic acid (PLGA) MBs encapsulating Texas Red dye are fabricated by a modified double-emulsion process. Simultaneous ultrasound and fluorescence imaging are achieved using Texas Red encapsulated MBs. The MBs are conjugated with Avastin, an antiVEGF antibody for treating neovascular age-related macular degeneration (AMD). The conjugation efficiency is characterized by enzyme-linked immunosorbent assay (ELISA). The efficiency for targeted binding of Avastin-conjugated MBs is characterized by microscopic imaging. Our work demonstrates the technical potential of using multifunctional MBs for targeted delivery of antiVEGF therapy in the treatment of exudative AMD.

Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.

Electrospray of multifunctional microparticles for image-guided drug delivery

Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA) microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.