Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia.

Retinal gene therapy is increasingly recognized as a novel molecular intervention that has huge potential in treating common causes of blindness, the majority of which have a genetic aetiology1-5. Choroideremia is a chronic X-linked retinal degeneration that was first described in 18726. It leads to progressive blindness due to deficiency of Rab-escort protein 1 (REP1). We designed an adeno-associated viral vector to express REP1 and assessed it in a gene therapy clinical trial by subretinal injection in 14 patients with choroideremia. The primary endpoint was vision change in treated eyes 2 years after surgery compared to unoperated fellow eyes. Despite complications in two patients, visual acuity improved in the 14 treated eyes over controls (median 4.5 letter gain, versus 1.5 letter loss, P = 0.04), with 6 treated eyes gaining more than one line of vision (>5 letters). The results suggest that retinal gene therapy can sustain and improve visual acuity in a cohort of predominantly late-stage choroideremia patients in whom rapid visual acuity loss would ordinarily be predicted.

Vector Shedding and Immunogenicity Sampling for Retinal Gene Therapy.

There has been recent growth in the number and magnitude of clinical trials for various forms of retinal gene therapy. Because of regulatory requirements, and to better understand vector safety profiles, there is a need for standardised and effective methods to collect, process, and store biological samples taken from trial patients that can be used to assess the dissemination of the vector within bodily fluids and any systemic cellular and humoral immune responses.

Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema.

PURPOSE: Pegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME. METHODS: Macular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 µm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST. RESULTS: Thirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046). CONCLUSION: In this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course.