Partial degeneration of photoreceptors at the fovea combined with abnormally reduced light sensitivity in the remaining photoreceptors
15,25,26 are the major reasons for reduced visual acuity in most patients with
RPE65-LCA.
15,27–31 When examined cross-sectionally, patients with more abnormal acuity tend to show greater eye movement abnormalities,
15 but fixation and nystagmus characteristics of
RPE65-LCA have not been studied in detail. We made oculomotor recordings of subjects by using direct retinal imaging monocularly in fully dark-adapted, untreated eyes in a dark room while viewing a stationary target brighter than the visibility threshold of each tested eye.
9,11,12,15 Five
RPE65-LCA eyes demonstrate the spectrum of oculomotor abnormalities observed under these conditions (
Figs. 1A–F). Patient P15 at age 18 with 20/80 acuity and P11 at age 27 with 20/40 acuity showed examples of minor oculomotor abnormalities with foveal fixation. The waveforms had small amplitudes (<1° excursion) and fast movements (“jerks”) occurring at 2.0 Hz for P15 and 1.8 Hz for P11 (
Figs. 1B,
1C). Fixation instability was 0.8° for both patients, implying that the center of the fixation target fell within 0.8° of the center of the anatomical fovea more than 95% of the time during a typical recording epoch of 10 seconds. Patient P1 at age 24 with 20/250 acuity also showed foveal fixation but with a larger amplitude (~2°) of diagonally beating (1.9-Hz) jerk nystagmus (
Fig. 1D); fixation instability was 1.9°. Patient P5, on the other hand, demonstrated a more severe stage of
RPE65-LCA. At age 20 with 20/2000 acuity, she showed more of a pendular nystagmus waveform (3.3 Hz) with horizontal as well as vertical components of ~4° amplitude and a mean fixation location centered at ~2° superonasal to the fovea; fixation instability around the extrafoveal fixation locus was 2.6° (
Fig. 1E). Fifth, P7 at age 15 with 20/250 acuity showed both small and large amplitudes (up to 6°) of nystagmus with jerk and pendular components beating (4 Hz) mostly horizontally across the anatomical fovea (
Fig. 1F); fixation instability was 5.1°. In summary,
RPE65-LCA patients viewing a visible stationary target under controlled adaptation and ambient conditions showed a range of eye movement abnormalities from barely detectable nystagmus with less than 1° amplitude to more severe forms with greater than 6° amplitude beating as fast as 4 Hz frequency.