UC Berkeley

Myopia or nearsightedness is a condition in which the axial length of the eye is too long relative to its optical focal length. This condition is reaching epidemic levels worldwide, and has become a tremendous public health burden. Myopia is one of the leading causes of vision loss and high myopia significantly increases the risk of permanent blindness. Consequently, myopia cannot be considered as a benign condition and early interventions aimed at slowing down or even stopping the progression of myopia rather than merely correcting the associated optical focusing error is of great importance.

The consistent evidence from animal model studies showing that imposed hyperopic defocus, if sustained, comprises an effective myopogenic stimulus, accelerating eye growth, while imposed myopic defocus slows ocular elongation, has motivated clinical studies using bifocal and progressive addition spectacles for myopia control. While these studies, reviewed in Chapter 2 of this dissertation, failed to provide convincing evidence for a clinically significant treatment effect, i.e., slowed myopia progression; smaller scale, non-randomized studies using multifocal soft contact lenses and orthokeratology lenses have shown much more promising effects in terms of slowing myopia progression. However, the mechanism(s) underlying the latter anti-myopia treatment effects are poorly understood, thereby limiting their further refinement. In addition to the aforementioned systematic review of relevant clinical evidence for optical interventions for myopia control, this dissertation described 3 other studies using chick model, representing efforts to further understand how multifocal optical environments affect normal ocular development, specifically the process of emmetropization. These manipulations have also been used as a tool to investigate the mechanism underlying the myopia controlling effect of the novel contact lens applications referred above.

Chapter 2 describes a systematic review and meta-analysis performed on randomized controlled trials investigating the effects of three traditional optical interventions, bifocal and progressive addition spectacles, and rigid contact lenses, all believed to control myopia progression, based on anecdotal evidence. The overall treatment effect was estimated to be only small and clinically insignificant. A number of reasons were proposed to explain the discrepancy between the results of related animal studies and these clinical trials - strong support for optical control of myopia from the former studies and inconclusive results from the latter studies. Poor compliance to the spectacle corrections in clinical studies, inaccurate measurement of adherence to the treatments, inadequate and potentially, ambiguous classification systems for clinical myopia, and potential flaws in the optical designs are likely to have contributed to the discouraging results from the clinical trials.

Chapter 3 describes the first of three studies in which the chick model was used to test the effects on ocular growth of a series of custom-designed 2-zone multifocal "spectacle" lenses. This and the two follow-up studies using this model have the following merits; they made use of standardized experimental paradigms and objective methods of measurement to track ocular changes. The first study applied the lenses in a simple experimental paradigm, in which monocular lenses were attached to the normal eyes of young chickens. The 2-zone lenses included a plano zone, either in the center or peripheral surround, with either positive or negative power (+5 or -5 D) incorporated into the other zone. The size of the central zone was also allowed to vary, to control the size of the unifocal central and peripheral retinal areas, and intermediate multifocal zone, as was the placement of the powered zone, i.e. in the center or periphery of the lenses. Single vision lenses were included as a control treatment. Two important observations from this study were that 1) peripheral optical defocus can influence both peripheral (off-axis) and central (on-axis) refractive error development and 2) the inhibitory effect on axial ocular growth of myopic defocus imposed using 2-zone lenses (positive zones) could exceed that induced by single vision lenses of the same power. These results suggested complex interactions between adjacent retinal regions, with the peripheral retina apparently able to decode optical defocus, as well as complex interactions between the eyes own optical aberrations and those of the 2-zone lenses, which introduced large amounts of spherical aberration.

Chapter 4 described a closely related study in which subsets of the same 2-zone lenses were tested on eyes that had undergone surgical manipulations (sectioning of the ciliary nerve, CNX or iridectomy, ID) to investigate the influence of the pupil size of the eye as well as accommodation on the effects of the 2-zone lenses. Both were uncontrolled in the first study; yet create a dynamic optical system on which the multifocal optical environment was imposed. The ID surgery produced a fixed dilated pupil without any effect on accommodation (confirmed in another study, reported in Appendix I), while the CNX surgery produced a similarly enlarged pupil while also eliminating accommodation. This study revealed pupil size to be a critical factor in the treatment effects of 2-zone lenses, likely to reflect at least in part, its influence on the optical experience of various retinal zones (center to periphery), and also suggested a significant role of accommodation in the decoding of imposed optical defocus stimuli, in this case, complex multifocal optical stimuli.

Chapter 5 described a third study which attempted to develop a clinically more relevant scenario; specifically, 2-zone lenses that incorporated two different negative powers (-5 & -10 D) in two optical zones (center & periphery or vice versa), were tested on both normal eyes and eyes made myopic before being fitted with one of the 2-zone lenses. The latter combination was intended to simulate the ocular conditions created when concentric multifocal contact lenses, i.e. with a near addition, are prescribed to human myopes, one of the novel, myopia control treatments currently being explored. When the 2-zone lenses were fitted to normal eyes, they induced myopia, of a magnitude falling between the values expected, had single vision lenses of the same powers been used. However, on myopic eyes, the lenses had a strong myopia inhibiting effect with the already induced myopia undergoing substantial regression. This result supports the further investigation of appropriately designed concentric multifocal contact lenses for the control of myopia progression.

In summary, the studies reported in this dissertation indicate complex interactions between central and peripheral retinal regions in decoding and responding to complex defocus signals as well as critical influences of pupil size and accommodation on these processes. The strong and consistent inhibitory effects on ocular growth of concentric 2-zone lenses incorporating a zone of either positive power or a near addition, 2-zone designs lend plausibility to the notion of using custom-designed novel optical treatments for the control of myopia progression.