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S um m a r y Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investiga t ed the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carry- ing RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477). Three patients with LCA2 had an acceptable local and systemic adverse-event pro- file after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study pro- vides the basis for further gene therapy studies in patients with LCA.

To the Editor: Leber's congenital amaurosis, a common cause of blindness in infants and children,1 recently became the first human genetic retinal disease to show improved vision in response to tre...

In this issue of the Journal, two groups of investigators — Bainbridge et al.1 and Maguire et al.2 — describe the first results of separate clinical trials investigating the short-term safety and preliminary efficacy of gene therapy for Leber's congenital amaurosis. Both groups present short-term data (12 months and 5 months, respectively) on three patients with Leber's congenital amaurosis in each study; the patients were enrolled in trials of recombinant adeno-associated viral delivery of the human retinal pigment epithelium-specific 65-kDa protein gene (RPE65), which was administered as a subretinal injection during vitrectomy. Originally described by Leber in 1869, . . .

Current ocular imaging techniques provide extraordinarily high-resolution visualization of the retinal layers, amounting to what has been called in vivo microscopy. Combine this with a battery of sophisticated retinal-function tests, and the retina becomes unusually accessible in the evaluation of trials of retinal gene therapy for the treatment of conditions such as Leber’s congenital amaurosis. Leber’s congenital amaurosis is a group of inherited retinal dystrophies associated with blindness early in life and can be caused by mutations in at least 19 different genes. Loss-of-function mutations in one of these genes, RPE65, account for 5 to 10% of recessive Leber’s . . .

The retina, the transparent neural tissue lining the interior of the eye, is the initial receptor for visual stimuli. Exciting progress has been made in many areas of retinal investigation, from genetic breakthroughs in retinoblastoma and retinitis pigmentosa to sophistication in the medical and surgical therapy of retinal diseases. This article reviews recent clinical developments in diabetic retinopathy, retinal detachment, retinal manifestations of the acquired immunodeficiency syndrome (AIDS), and age-related macular degeneration. Classically, the retina is separated into 10 layers on light microscopy (Figure 1)1. The photoreceptors, consisting of rod and cone cells, are located near the outer surface . . .

Apoptosis causes the death of photoreceptors in macular degeneration and retinitis pigmentosa and the death of retinal ganglion cells in glaucoma. Receptors for erythropoietin are present in both t...