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Ординатура / Офтальмология / Английские материалы / Myopia Animal Models to Clinical Trials_Beuerman, Saw, Tan_2009.pdf
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154 C. D. Luu and A. W. L. Chia

a significant correlation between first-order kernel mfERG responses and refractive error. The findings showed that the amplitude of the mfERG decreased as the degree of myopia increased. The mfERG P1 amplitude is negatively correlated with the axial length. The mfERG P1 implicit time increased with an increase in axial length and severity of myopia.

Effect of Long-Term Atropine Usage on Retinal Function

To date, only atropine eye drops have been shown to have a consistent effect on the retardation of myopia progression.28,29 There are, however, at least two potential chronic side effects associated with the long-term use of atropine. Firstly, accumulation of atropine over a period of time might be toxic to the neural retina. Secondly, constant pupillary dilatation will increase the amount of light entering the eye and could theoretically cause photic damage to the retina.

Luu et al.30 recorded the mfERG responses in children (n = 48) receiving atropine eye drops once daily for two years, and in those receiving placebo eye drops (n = 57) for a similar duration. Their results showed that there was no significant difference in the mfERG response amplitudes and implicit times between the atropine treated and placebo control groups, suggesting that atropine use for two years has no significant effect on retinal function.

Macular Function Associates with Myopia Progression

Studies have examined the relationship between macular function changes and the rate of myopia progression. Chen et al.14 studied the multifocal oscillatory potential (mfOP) changes in emmetropes, stable myopes, and progressing myopes. They found that progressing myopes had significantly shorter mfOP implicit times compared to emmetropes and stable myopes. There were, however, no statistically significant differences in OP amplitudes between the groups.

Luu et al.31 examined the mfERG responses of 81 children (aged 9–10 years) with myopia (mean spherical equivalent refraction ranging from 1.00 D to 5.88 D), and they showed that the initial mfERG P1 amplitude within the central 5 degrees was significantly associated with the subsequent two-year myopia progression rate, but not with the initial degree of

155 Retinal Function

myopia. The mfERG P1 amplitude of the central ring was significantly reduced in a high progression group, defined as a progression rate of at

least 1 D per two years, compared to a medium progression group (progression rate of >0.25 D and <1 D per two years) or a low/no progression

group (progression rate of ≤0.25 D per two years). Responses from rings 2–5 (central 5 to 35 degrees retina) were similar for all the progression groups. No significant differences in mfERG response implicit times were found in any of the progression groups at any of the locations tested.

Factors Associated with ERG Changes in Myopia

Although the reduction in ERG response in adults with myopia has been well recognized, the actual mechanisms of ERG reduction in myopia are unclear.

It has been suggested that the reduction in ERG amplitudes seen in adults with myopia may be owing to a reduced image size and decreased retinal illumination, known as the optical factor, as a result of axial elongation of the eye.32 By examining the stimulus intensity response function, Kawabata and Adachi-Usami23 claimed that decreased retinal illuminance did not explain the reduced ERG response because the responses of the high-myopic eye had much lower saturated amplitudes than for the emmetropic eye.

It has been suggested that the ERG amplitudes are reduced in persons with myopia because of a higher resistance between the source of the current (the retina) and the place where the current is measured (the cornea). It is believed that increased distance between the electrical source and the recording corneal electrode, also referred to as the electrical factor, due to a larger eyeball, caused an increase in the ocular resistance to electric current.9,33

Decreased retinal photoreceptor density, morphological changes in the photoreceptor outer segment, and photoreceptor dysfunction have been postulated as the causes for ERG reduction in myopia.24,34 Altered neural processing could result, in part, from retinal stretching in the enlarged myopic eye, which may produce both increased retinal cell spacing and post-receptoral retinal dysfunction, and lead to a decrease in retinal sampling.34 Another mechanical attribute of the eye in axial myopia might be an increase in the subretinal space and subsequent reduction in photoreceptor response.34

156 C. D. Luu and A. W. L. Chia

Luu et al.25 examined the relationship between ERG amplitude and myopia in adults and children with various degrees of myopia. While their results confirm that there is a significant correlation between the refractive error and ERG amplitude in adults with myopia, they also discovered that such a relationship is absent in children with myopia. In light of the results obtained from this study, the optical and electrical factors are unlikely to be the cause of the ERG reduction because of the absence of any relationship between ERG amplitudes and the severity of myopia in children. Similarly, with photoreceptor morphological and functional changes in myopic eyes, a good correlation between ERG amplitude reduction and severity of myopia would be expected irrespective of the subject’s age. These data provide strong evidence that the reduction of ERG response seen in adults with myopia is not directly due to the severity of myopia. The lack of correlation between ERG amplitude and the degree of myopia in children suggest that other mechanisms must be responsible for the reduction in ERG. It is postulated that the reduction in ERG response seen in the adult group may be owing to retinal function modifications that are associated with long-standing myopia.

Conclusion

There are demonstrable changes in retinal function in subjects with myopia. In studies involving Ganzfield electroretinography, there is a progressive reduction in both a-wave (photoreceptor) and b-wave (bipolar cell) responses in adult subjects with increasing myopia, and reduction in b-/a-wave amplitude ratio in those with very high myopia. Similar reduction in P1 responses of the mfERG were seen in the macular regions. The exact nature of ERG reduction in myopia remains unknown. Gradual changes do occur in myopic fundi over time with the development of posterior staphyloma, peripalliary atrophy, and myopic macular degeneration, and there may be clinically significant visual loss in some individuals.

Future directions include a better understanding on what, when, and where functional changes occur within the myopic retina over time. Of interest is also whether these changes precede or even induce anatomical changes and whether they can be used to identify individuals at greatest risk of developing high myopia. Electroretinography can also be used to

157 Retinal Function

monitor the safety and efficacy of new drug therapies for myopia as they become available in the future.

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Section 3

Genetics of Myopia

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