Amblyopia occurs when there are abnormal visual experiences during the sensitive period of visual development, leading to the reduction of one or both eyes’ BCVA to below age standard. In this study, we used OCT and P-ERG to investigate retinal structural and functional changes in adult patients with monocular anisometropic or strabismic amblyopia. The analysis of RNFL thickness comprised of four regions and P-ERG was recorded and analyzed by two different modes, biasing the parvocellular pathway and magnocellular pathway respectively. We found GCC and all sectors of RNFL thickness except the temporal sector significantly increased and P50 and N95 amplitudes significantly reduced in the amblyopic eyes of the AA group compared with the fellow eyes while no significant changes of OCT and ERG parameters could be seen in SA group.
Inconsistent results have been reported by different scholars in observing the changes of retinal structure in amblyopia by using OCT. Altintas [7] et al. and Al-Haddad et al. [8] found that the RNFL thickness of amblyopic eyes was not significantly different from the contralateral healthy eyes in either adult or children patients with anisometropic amblyopia. Furhtermore, Firat et al. [20] reported that RNFL thickness in the amblyopic eyes of children was not significantly different from the healthy eyes in the normal control group. But Yoon et al. [9] found that RNFL was significantly thicker in the amblyopic eyes than the contralateral healthy eyes in anisometropic amblyopic children. We speculated that the cause of the inconsistency was that the total peripapillary RNFL had been analyzed in previous studies whereas different regions of RNFL might vary in amblyopia. So we analyzed RNFL in four sectors separately in this study and found RNFL thickness in the nasal, superior and inferior sectors significantly increased. At the same time, the temporal sector of RNFL, where the maculopapillary bundle is located, in amblyopic eyes is thinner. The maculopapillary bundle is believed to be responsible for the central visual signals from the macula to the optic nerve. Previous studies suggested that in amblyopia, central vision is impaired; in other words, damage occurs mainly in the center of the macula and central visual pathways with no significant change to peripheral vision when compared to the contralateral eyes. We speculated that the thinning of RNFL in the maculopapillary bundle may cause degeneration of central vision and corresponding excessive ganglion cell atrophy or apoptosis. Thickening in RNFL layer in other sectors might be due to the blocking of normal ganglion cells’ apoptosis after birth [10].
Changes in ganglion cells after birth are considered to be one of main reasons for retinal structural alteration in amblyopia [10]. Apart from RNFL, the GCC layer includes inner plexiform layers, ganglion cell body, and nerve fiber. Tugcu et al. [13], using OCT to measure GCC thickness, found that in strabismic amblyopia patients (aged 3–13 years), the GCC layer was thicker when compared to the fellow healthy eyes. However, Park et al. [12] found that patients with amblyopia had significantly reduced GCC layer average thickness than the contralateral healthy eyes. The present study found an increase in the thickness of the GCC layer in adult patients with anisometropic amblyopia compared with the contralateral eyes, but no statistically significant change in strabismic amblyopia. This is consistent with the study by Yen et al [10] that suggested that normal apoptosis of retinal ganglion cells was blocked after birth in amblyopia, which can lead to an increase in RNFL thickness. Szigeti A et al. [11] suggested that if Yen and others’ hypothesis was correct, then the suppression of retinal ganglion cells’ apoptosis would not only affect the thickness of the RNFL, but also result in a thickening of the GCC layer. These studies provided evidence that the mean GCC thickness would increase in amblyopia.
Besides the structural changes that could be observed in the amblyopic eyes, P-ERG was used in exploring the functional changes of the retina in our study [25]. The P50 wave of P-ERG was suggested to reflect the function of retinal ganglion cells [26] while the N95 wave was believed to be a specific indicator of retinal ganglion cell function [27–28] and N95 amplitude reduction implied function defects of retinal ganglion cells. There were many studies on patients with amblyopia in P-ERG changes, but results still remained inconsistent. Tepping et al. [21], Guttob et al. [15] and Hess et al. [16] found no significant difference between amblyopic eyes and the normal control eyes in either amplitude or latency of P50 and N95. Tugcu B et al. [13] and Arden et al. [14], using the same stimulation patterns, found that among patients with amblyopia, there were no significant differences in the amblyopic eyes’ P-ERG latency compared to the fellow eyes, but P50 amplitude in the amblyopic eyes declined significantly when compared to the normal control eyes, indicating the decline of retinal ganglion cell function. Manny et al. [22], also under the same stimulation patterns, found that P50 amplitude decreased in amblyopic eyes compared to the contralateral healthy eyes and pointed out that this may be due to the amblyopic eyes’ retinal ganglion cell function decline. In this study, we used a low temporal frequency - high spatial frequency mode (HSLT) and a high temporal frequency - low spatial frequency mode (ISHT) to respectively bias parvocellular pathway and magnocellular pathway. These two visual transmission pathways are relatively separated from the retina to LGN, anatomically and functionally [23, 24]. We found that both P50 and N95 wave amplitudes declined in patients with anisometropic amblyopia under the parvocellular pathway biased stimulation, while no magnocellular pathway impairments could be observed in anisometropic amblyopia. These results suggested that in the patients with anisometropic amblyopia, the damage might exist in some of retinal ganglion cells that were responsible for signal transmission of the parvocellular pathway.
Ganglion cell development requires the stimulus of a clear optical image [26]. In anisometropic amblyopia, the eyes’ refractive state does not allow a clear image to be projected onto the retina. This may affect the normal development of the ganglion cells leading to structural and functional abnormalities, which may in turn affect the photoelectric signal conversion or signal transmission of the retina, resulting in amblyopia development. In strabismus amblyopia patients, neither GCC nor RNFL thickness was significantly different in the amblyopic eyes compared with the fellow eyes, and also no statistically significant difference existed in amplitude and latency of P50 and N95 when compared with the fellow eyes. Our results are consistent with the results of Altintas et al. [7] and Kee et al. [17]. These findings also support the hypothesis that the mechanism of anisometropic amblyopia is different from strabismic amblyopia. The visual pathway damage of strabismic amblyopia may be mainly in the visual cortex [29], and the retina may be as normal as the fellow normal eyes.
Since the present study enrolled subjects who were all over the age of 18, the confounding factor of age has been excluded in comparison with previous studies. Axial length was not corrected during analysis because the authors did not find a significant difference between the amblyopic eyes and the fellow eyes in AL. No significant correlation between axial length and OCT, P-ERG indicators was established. These results are consistent with the findings of Szigeti A [11].