Treatment Effect of Levodopa in Amblyopia Evaluated by Functional MRI

investigation of the changes of visual cortical activity in patients with amblyopia after the levodopa treatment. Method Four amblyopes aged from 13 to 17 years old were enrolled in this study. The indications, risks and benefits of the procedures were well explained to the patients or their family. The best-corrected visual acuities (BCVAs) of their sound eye were all 1.0, while that of their amblyopic eye were 0.3, 0.3, 0.04 and 0.3, respectively. All patients received levodopa and part-time (3 hours/day) occlusion of the sound eye. Levodopa/carbidopa, in the dosage of 0.5/0.12 mg/kg was administered orally three times per day for 7 weeks. FMRI experiments were performed on a 1.5-T Magnetom Vision MRI scanner. Two separate fMRI scans were performed on sound eye and amblyopic eye, respectively. Each scan contains four resting-state blocks, interleaved by three stimulation-state blocks. Each block lasts for 30 seconds. A full field circular checkerboard flashing at 8 Hz was presented on a goggle display system as the visual stimuli. The visions of each subject were corrected to the BCVAs using lenses during the experiments. The subject’s head was restrained in a molded plastic facial mask to reduce motion. A single-shot T2*-weighted gradient-echo echo-planar imaging (EPI) sequence was used for fMR imaging. 17 slices along the direction of the calcarine fissure was imaged to cover the visual areas and most other parts of the brain. The imaging parameters were as follows: slice thickness=5mm, in-plane spatial resolution=3.3 × 3.3mm 2 , number of measurement=105, and TR/TE/FA=2000ms/60ms/90 0 . For anatomical detail, a high-resolution (1x1mm 2 ) T1-weighted image was acquired with the same slice thickness and location being identical to that used in the functional imaging. For data processing (7), activation maps were calculated by comparing images acquired during the stimulation states and those during the resting states, using an unpaired students’ t-test with a threshold of 2.4 (p<0.01). For each subject, the volume of significantly activated voxels within the visual cortex were used to compare the neuronal activity induced by visual stimulation through the sound eye and the amblyopic eye, before and after the treatment. The ratio of the activation volumes from the amblyopic and sound eye stimulation was calculated to further investigate the treatment effect. Results Fig. 1 shows the functional maps of visual cortical areas from one of the patients, before and after levodopa medication. With the sound eye stimulation (Fig. 1a, b), approximately identical locations and volumes of the activated voxels were observed before and after the treatment. For the amblyopic eye stimulation, no significant activation was detected before the treatment (Fig. 1c). However, after the treatment, significant activation was observed in the visual areas (Fig. 1d). Table 1 summarizes the volumes of the activated voxels in the visual cortical areas detected in all the four patients. With the sound eye stimulation, no significant difference was found in the fMRI volume measurement before and after levodopa medication (p=0.20). With the amblyopic eye stimulation, greater volume of activation was found after than before the administration of levodopa. However, p=0.09 did not reach the statistical criteria. The volume ratio from the amblyopic and sound eye stimulation showed a statistically significant improvement (p<0.05) after levodopa medication. Post-treatment BCVAs of the patients’ sound eyes were 1.0, and that of their amblyopic eyes were 0.4, 0.5, 0.04, and 0.5, respectively. Improvement of BCVAs was observed to be in good agreement with the fMRI results.