Retinitis pigmentosa (RP) is a collection of genotypically and phenotypically diverse eye disorders, all of which attack the rods and cones within the retina. This inherited disease is often identified by its main clinical features, which typically include symptoms of poor night vision, visual field loss, and flickering lights. As the disease progresses and more photoreceptors are lost, patients experience an indolent, progressive constriction of their visual field until legal and functional blindness occurs, typically by age 40. Loss of central vision occurs in very advanced RP or in atypical RP. Upon ophthalmic examination, a triad of clinical findings is typically noted: attenuation of retinal blood vessels, “bone spicule” clumping and mottling of the retinal pigment epithelium (a single layer of pigmented cells that nourishes the retina photoreceptors), and optic nerve head pallor. All of these findings are a direct result of the main pathophysiologic action of RP, atrophy of the photoreceptor layer.
Age-related Macular Degeneration
The RP population, particularly those with vision poor enough to qualify for a retinal prosthesis system (RPS), is rather small. A paper by Grover and colleagues (1999) examined the visual abilities of 982 patients with RP, of whom 25 percent had visual acuity of 20/200 or worse in both eyes. Many of these patients had more vision than light perception, so they would not meet the U.S. Food and Drug Administration (FDA) indication for the approved Argus II RPS device (which requires light perception only, or worse). Thus, the broader goal for most of the companies developing retinal prostheses would be for implementation in more common disease states.
The most logical of these is late-stage age-related macular degeneration (AMD), because many of the pathologic aspects of RP for RPS can also be found in AMD, namely physiologic damage limited to the outer retina. AMD is the leading cause of irreversible visual loss in industrialized countries, and in the United States, it accounts for about half of severe sight loss. However, the number of patients with advanced AMD who could possibly benefit from an RPS is much smaller. Although the etiology is incompletely understood, AMD develops as a result of deposition of cellular debris—including lipids, amyloid, complement factors, and other components—in Bruch’s membrane.
Retinal Prosthesis Systems
Multiple types of ocular prosthetic devices are under development. The devices have focused on stimulating different parts of the visual pathway, including the visual cortex,8 the optic nerve, and the retina when placed in the suprachoroidal, epiretinal, and subretinal spaces. Of the seven RPS devices for which there was at least one published article describing a study in humans, the only one to date to receive FDA approval is the Argus II epiretinal RPS (Second Sight Medical Products, Inc., Sylmar, CA). Another device originating in the United States is the subretinal Artificial Silicon Retina (ASR), developed by Optobionics (Glen Ellyn, ES-1
IL). The subretinal Alpha-IMS was created by Retina Implant AG (Reutlingen, Germany). Another German manufacturer is Fraunhofer IMS Biohybrid Systems (Duisburg, Germany), which developed the epiretinal EPIRET3 device. The IRIS device (also epiretinal) began development in Germany but is now produced by the French manufacturer Pixium Vision (Paris, France). The suprachoroidal Bionic Eye RPS comes from BionicVision in Parkville, Victoria, Australia. Nidek Co., Ltd. (Gamagori, Japan), produces the Suprachoroidal Transretinal Stimulation (STS) Artificial Vision System. These devices are discussed in detail in the body of this report.
We also identified three additional devices subjected to preclinical tests. The Boston Retinal Implant Prosthesis (Visus Technology, Inc., Boston, MA) uses a subretinal array of 16 electrodes that receives energy and data from an eyeglass-mounted video camera and radiofrequency coil, with assistance from a controller that performs image signal processing. Another American device, the Photovoltaic Retinal Prosthesis (Stanford University Palanker Laboratory) has a subretinal array of thousands of photodiodes that convert light pulses to bi-phasic pulses of electric current. From Japan, the Okayama University-Type Retinal Prosthesis uses a unique approach with photoelectric dye molecules coupled to polyethylene film.
Alternative Treatments for Retinitis Pigmentosa and Age-Related Macular Degeneration
For RP, the current state of care is generally supportive in nature, focusing on maximizing the visual acuity of a patient (i.e., performing cataract surgery) and offering training with low-vision aids and services helping patients to function within their limited visual capacity. Some pharmacologic agents approved for other conditions may potentially maximize visual acuity in RP patients. (For example, the topical carbonic anhydrase inhibitor dorzolamide, used in open-angle glaucoma or ocular hypertension, may have an ancillary benefit of reducing cystoid macular edema in RP patients who have this feature of the disease). The absence of RP-specific FDA-approved medications is not for lack of effort, with most of the past focus being on nutritional supplements. Supportive care is offered to patients with nonexudative AMD. For those patients who smoke, they are advised to quit. Those with intermediate or advanced disease may be advised to take antioxidant vitamins and minerals to reduce the risk of progression. For the nonexudative patients who have progressed to exudative AMD, the main treatment is vascular endothelial growth factor (VEGF) inhibitor therapy.
Scope and Key Questions
The scope of this review is defined in Table A according to the PICOTS framework (population, intervention, comparators, outcomes, timing, and setting; see Table A). Key questions (KQs) appear below. Figure A presents an analytic framework that depicts KQs, populations, treatments, patient-centered outcome measures, and associated psychometric properties.