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Vittorio Porciatti, Fawzi Abukhalil, Byron L. Lam, William J. Feuer, John Guy; LHON Gene Therapy Trial: 18 Month Serial Pretreatment Evaluations. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4881.
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© ARVO (1962-2015); The Authors (2016-present)
To describe serial changes of visual function, electrophysiologic RGC function and optic nerve structure of affected LHON patients and unaffected carriers with the G11778A mutation in mtDNA from baseline to 18 months of study entry.
Patients with visual loss and unaffected maternally related family members genotyped with G11778A mtDNA underwent serial examinations (SAP, PERG, OCT) every 6 months for 18 months. Of 94 total participants, 26 affected patients (mean age 32 years) and 22 carriers (mean age 41 years) completed their 18 month follow-up visits. Measurements of both eyes were averaged and their means compared over time with analysis of variance, orthogonal polynomial tests, and post-hoc LSD tests.
In affected patients, the baseline mean PERG amplitude (0.46 µV) was reduced compared to the expected normal for the age group (1.12µV), and remained stable 0.45 µV at 6 months, 0.45 µV at 12 months and 0.46 µV at 18 months (p=0.96). Cirrus OCT RNFL thickness diminished slightly from a baseline of 64 µm (p overall=0.008, pBL vs 6, 12, 18 mos all <0.05), but remained stable thereafter with 56 µm at 6 months, 54 µm at 12 months and 55 µm 18 months (all p>0.18). SAP mean defect was stable with -23 db at baseline, -25 db at 6 month, -24 db at 12 months and -24 db at 18 months (p=0.63). In carriers, the mean baseline PERG amplitude (1.03 µV) was not reduced compared to the expected normal for the age group (1.02 µV). However, it decreased to 0.90 µV at 6 months (p overall <0.001), 0.87 µV at 12 months and 0.80 µV at 18 months (p linear decrease <0.001). Baseline RNFL thickness (93 µm) was normal and remained stable with 92 µm at 6 months, 91 µm at 12 months and 92 µm at 18 months (p=0.27). SAP mean defect was stable with -1.36 db at baseline, -1.18 db at 6 months, -1.19 db at 12 months and -1.25 db at 18 months (p=0.91).
In affected patients, SAP, PERG and OCT measurements are steadily reduced to about half of normal values over 18 months; thus relatively small improvements over time following gene therapy should be measurable. PERGs of unaffected carriers are larger than those of affected patients but show a measurable progressive decline in RGC function without any change in structure or visual function. Further follow-up will reveal whether the PERG amplitude drops will predict conversion to the phenotype. If so then carriers may be treated before loss of vision.
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