Low- and Medium-Dose Gene Therapy in Patients with Prior Unilateral LHON Does Not Prevent Further Visual Loss in the Treated Eye (S16.006)

Objective: To report the visual results after a single unilateral, intravitreal injection of a self-complementary adenoassociated virus serotype 2 containing a wild-type nuclear-encoded ND4 subunit to five G11778A LHON subjects with acute unilateral disease (20/40 or better ) and 20/200 or worse in the fellow eye. Background: We had previously reported that many patients with bilateral visual loss from LHON who received low (1X) and medium dose (5X) gene therapy to the worse eye within a year after their bilateral visual loss had significant gains of visual acuity, but most of those treated after a year did not (Ophthalmology. 2017 124:1621–1634). Design/Methods: Clinical testing included ETDRS visual acuity, Humphrey visual fields (30–2), OCT, pattern ERG and neuro-ophthalmic examinations. Blood samples were screened for neutralizing antibodies prior to and after treatment. Visual acuity changes from light perception to hand movements or hand movements to counting fingers was assigned a value of 15 letters. Results: In acute unilateral cases with good vision at the first baseline examination (20/40 or better) there was an average loss of 45.6 letters in the gene therapy-injected eyes at last follow-up relative to the second baseline examination. An average loss of 8.6 letters was seen between baseline exams prior to gene injections. The 3 unilateral cases described in our prior natural history study lost an average of 20.7 letters (JAMA Ophthalmol. 2014 132(4):428–36). OCT RGC+IPL thickness in treated eyes of unilaterals was 69.8 um the day prior to injections but 48.7 um in those who were 20/200 or worse for more than a year and 54.0 um in those with 20/200 or worse for less than a year. We have yet to test the high dose (20X). Conclusions: Low-medium dose gene therapy did not prevent deterioration of vision suggesting a planned higher dose may be needed perhaps due to the thicker RGC+IPL layers. Study Supported by: NEI 1U10EY023558 (Guy)and 1U10EY024247 (Feuer) Disclosure: Dr. Guy has nothing to disclose. Dr. Feuer has nothing to disclose. Dr. Davis has nothing to disclose. Dr. Porciatti has nothing to disclose. Dr. Lam has nothing to disclose. Dr. Yuan has nothing to disclose. Dr. Koilkonda has nothing to disclose. Dr. Gonzalez has nothing to disclose.