April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Gene therapy for choroideremia: Early functional and anatomical recovery after subfoveal vector injection
Author Affiliations & Notes
  • Markus Groppe
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
    Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  • Charles L Cottriall
    Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  • Jasleen Kaur Jolly
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
    Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  • Robert E MacLaren
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
    Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3295. doi:
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      Markus Groppe, Charles L Cottriall, Jasleen Kaur Jolly, Robert E MacLaren; Gene therapy for choroideremia: Early functional and anatomical recovery after subfoveal vector injection. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3295.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To report on early visual-functional and structural retinal recovery after subretinal injection using an adeno-associated viral (AAV) vector encoding Rab escort protein (REP)1 in six patients with a diagnosis of choroideremia.

Methods: Patients with genetically confirmed diagnosis of choroideremia underwent pre (PO) and postoperative visual function assessment with ETDRS vision chart (PO, 1d, 1 wk, 1 m, 6 m) and personalised microperimetry testing (PO, 1 m, 6 m) (Maia Centervue). Two patients with very advanced disease underwent additional microperimetry testing 1 day and 1 week post operatively. Anatomical changes were assessed with optical coherence tomography and SLO autofluorescence. The vector was delivered by subretinal injection after initial foveal detachment with balanced salt solution at a dose of 1010 genome particles (gp) in five patients and 6 x 109 in the sixth.

Results: The surgical procedure to not cause any adverse events. The average visual acuity (aVA) pre-treatment was 0.34 logMAR. One day after treatment the aVA dropped to 0.64. The effect was more marked in 4 patients with previously normal VA (0.06 to 0.46), whereas the two patients with poorer VA had a smaller drop in VA (0.94 to 1.02). One week after surgery the VA was only slightly reduced 0.38 and returned to baseline after 1 month (0.34). The return of vision was sustained in all patients, and the two patients with low VA improved at 1m, 6m, 1y (0.74, 0.62, 0.56). The mean retinal sensitivity of functional retinal areas across the cohort was 7.74dB before surgery. The sensitivity was unchanged 1 month after surgery (7.54dB) but improved to 8.85dB 6 months after surgery. Two patients with advanced disease (baseline 8.0dB) showed a reduction of retinal sensitivity one day after surgery, which recovered by 1w (7.54dB) and and further by 1m (7.95dB). The OCT examination showed complete absorption of the vector on day after surgery and no significant structural changes at 1m and 6m.

Conclusions: Subfoveal gene therapy with localised retinal detachment was controversially discussed due to fear of induced progression of retinal degeneration. The recovery of VA and retinal sensitivity 1w and 1m after foveal detachment in our study suggest that this method of treatment does not bear any adverse effects. Furthermore in patients with advanced disease an early improvement in function was noted. Future gene therapy treatment studies for macular/fovea involving diseases should consider subfoveal injection as a viable delivery method.

Keywords: 538 gene transfer/gene therapy • 696 retinal degenerations: hereditary • 462 clinical (human) or epidemiologic studies: outcomes/complications  
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