Zhaohui Hu wins ophthalmology prize for her medical student research day presentation

Tue, 09/22/2015 - 18:30

Zhaohui won a research presentation award for her presentation, "Why can’t patients with albinism see? Electrophysiology and structure of the central retina in albinism", at the Medical Student Research Day this past September.

Abstract:
Albinism is a congenital condition characterized by complete or partial absence of melanin pigmentation in the skin, hair and eyes. Most patients with albinism are legally blind (less than 20/200 vision). In addition to reduced visual acuity, nystagmus, strabismus, photophobia, decreased stereopsis, and amblyopia are usually present. Treatment is supportive since there is no way to improve the structure or function of the retina when they have formed incorrectly in utero. A pathognomonic feature of albinism is foveal hypoplasia, a mal-development of the macula in the central retina that can be detected on optical coherence tomography (OCT). The correlation between macular function, as measured by electrophysiology, and structure, as measured by OCT, is unknown in albinism. Understanding this relationship will offer clues to therapeutic strategies to improve vision in these patients.

Diagnostic OCT results in patients’ records were correlated with ERG and visual acuity. Patients were compared to controls using the nonparametric permutation test. 12 patients with a molecular genetic and clinical diagnosis of albinism were enrolled (7 males, 5 females, mean age=15.1 yrs). 11 normal controls were enrolled (3 males, 8 females, mean age=28.5 yrs). In mfERGs,7 out of 12 patients had Ring 1 (central) amplitudes within 1 SD of the normal controls (85+/-24 nV/deg2) in at least one eye, even in the absence of a visible fovea on OCT. All 12 patients had higher amplitudes in the central than peripheral rings. There was no correlation between visual acuity and Ring 1 amplitudes on mfERG. Compared to controls, patients had lower mfERG amplitudes and shorter latencies in the central ring (p=0.004, p=0.0074). Patients and controls were assigned to three age groups (6-15 yrs, 16-25 yrs, and 26-50 yrs). Within each group, patients still had lower mfERG central ring amplitudes than the controls. In ffERGs, greater central macular thickness (less well developed fovea) correlated with lower Ring 1 and 2 amplitudes on mfERG (p<0.05) and with lower a-wave amplitudes on ffERG in 3.0 light adapted, 0.01 dark adapted and standard combined response conditions (p<0.05), but not the 30 Hz flicker condition. There was no correlation between ffERG amplitudes and visual acuity. Patients averaged higher a-wave amplitudes than controls in all but the 30 Hz flicker condition (p≤0.01). Patients had shorter latencies in the scotopic 0.1 condition for a-wave and b-wave (p<0.02). Patients also had higher b-wave amplitudes in the light adapted 3.0 condition (p=0.03).In mice with albinism there was no difference in ffERG amplitudes (n=10) or retinal thickness on OCT (n=5) compared to the wild type control. The cone density across the retina was higher in the wild type control than albino (p=0.0004).

Our study shows for the first time that albinism patients with foveal hypoplasia on OCT still may have normal electrical activity in the central retina. On average, however, the central mfERG amplitudes are lower than normal controls while the ffERG amplitudes are higher. This suggests that more light reaches the retina in albinism patients, increasing ffERG amplitudes, however the central cones cannot respond normally to the detailed stimulus of the mfERG. We found a relationship between mfERG amplitude and OCT, but not visual acuity, which is consistent with previous studies showing no correlation between OCT and visual acuity. However our results are diametrically opposed to two reports of children under anesthesia who had no recordable mfERG spike in the central retina. The etiology of decreased vision in albinism is complex and requires more study, but absence of electrical activity in the central retina is not a proximal cause of vision loss.