The relationship of accommodation to myopia development and progression has been the subject of speculation and debate for many years. In this presentation some of the key findings from past research will be discussed along with recent data showing that accommodative behavior during optical treatment with multifocal contact lenses is related to treatment efficacy. The results will be discussed along with some possible strategies for improving treatment outcomes.

Studying the temporal integration of visual signals is crucial to understand how time spent on different visual tasks can affect emmetropization and refractive error development. In this study we assessed the effect of interrupting positive and negative lens-imposed defocus with brief periods of unrestricted vision or darkness. A total of forty-six marmosets were treated monocularly with soft contact lenses for 4 weeks from 10 weeks of age (OD: + 5D or − 5D; OS: plano). Two control groups wore + 5D (n = 5) or − 5D (n = 13) lenses continuously for 9 h/day. Two experimental groups had lens-wear interrupted for 30 min twice/day at noon and mid-afternoon by removing lenses and monitoring vision while marmosets sat at the center of a viewing cylinder (normal vision interruption, + 5D: n = 7; − 5D: n = 8) or while they were in the dark (dark interruption, + 5D: n = 7; − 5D: n = 6). The interruption period (30 min/day) represented approx. 10% of the total stimulation time (9 h/day). On-axis refractive error (RE) and vitreous chamber depth (VCD) were measured using an autorefractor and high frequency A-scan ultrasound at baseline and after treatment. Wearing + 5D lenses continuously 9 h/day for 4 weeks induced slowed eye growth and hyperopic shifts in RE in treated relative to contralateral control eyes (relative change, VCD: − 25 ± 11 μm, p > 0.05; RE: + 1.24 ± 0.58 D, p > 0.05), whereas − 5D lens wear resulted in larger and myopic eyes (relative change, VCD: + 109 ± 24 μm, p < 0.001; RE: − 2.03 ± 0.56 D, p < 0.05), significantly different from those in the + 5D lens-treated animals (p < 0.01 for both). Interrupting lens induced defocus with periods of normal vision or darkness for approx. 10% of the treatment time affected the resulting compensation differently for myopic and hyperopic defocus. Interrupting defocus with unrestricted vision reduced − 5D defocus compensation but enhanced + 5D defocus compensation (− 5D, VCD: + 18 ± 33 μm; RE: − 0.93 ± 0.50 D, both p > 0.05; + 5D, VCD: − 86 ± 30 μm; RE: + 1.93 ± 0.50 D, both p < 0.05). Interrupting defocus with darkness also decreased − 5D defocus compensation, but had little effect on + 5D defocus compensation (− 5D, VCD: + 73 ± 34 μm, RE: − 1.13 ± 0.77 D, p > 0.05 for both; + 5D, VCD: − 10 ± 28 μm, RE: + 1.22 ± 0.50 D, p > 0.05 for both). These findings in a non-human primate model of emmetropization are similar to those described in other species and confirm a non-linear model of visual signal integration over time. This suggests a mechanism that is conserved across species and may have clinical implications for myopia management in school-aged children.

The COVID-19 pandemic has been spreading across the globe for several months. The nature of the virus (SARS-CoV-2) with easy person-to-person transmissions and the severe clinical course observed in some people necessitated unprecedented modifications of everyday social interactions. These included the temporary suspension of considerable elements of clinical teaching at optometry schools worldwide. This article describes the challenges optometry schools were facing in early to mid 2020. The paper highlights the experiences of six universities in five countries on four continents. Strategies to minimise the risk of virus transmission, to ensure safe clinical optometric teaching and how to overcome the challenges presented by COVID-19 are described. An outlook on opportunities to further improve optometric education is provided.

Biofeedback training has been used to access autonomically-controlled body functions through visual or acoustic signals to manage conditions like anxiety and hyperactivity. Here we examined the use of auditory biofeedback to improve accommodative responses to near visual stimuli in patients wearing single vision (SV) and multifocal soft contact lenses (MFCL). MFCLs are one evidence-based treatment shown to be effective in slowing myopia progression in children. However, previous research found that the positive addition relaxed accommodation at near, possibly reducing the therapeutic benefit. Accommodation accuracy was examined in 18 emmetropes and 19 myopes while wearing SVCLs and MFCLs (centre-distance). Short periods of auditory biofeedback training to improve the response (reduce the lag of accommodation) was performed and accommodation re-assessed while patients wore the SVCLs and MFCLs. Significantly larger accommodative lags were measured with MFCLs compared to SV. Biofeedback training effectively reduced the lag by ≥0.3D in individuals of both groups with SVCL and MFCL wear. The training was more effective in myopes wearing their habitual SVCLs. This study shows that accommodation can be changed with short biofeedback training independent of the refractive state. With this proof-of-concept, we hypothesize that biofeedback training in myopic children wearing MFCLs might improve the treatment effectiveness.

The results of many studies in a variety of species have significantly advanced our understanding of the role of visual experience and the mechanisms of postnatal eye growth, and the development of myopia. This paper surveys and reviews the major contributions that experimental studies using animal models have made to our thinking about emmetropization and development of myopia. These studies established important concepts informing our knowledge of the visual regulation of eye growth and refractive development and have transformed treatment strategies for myopia. Several major findings have come from studies of experimental animal models. These include the eye's ability to detect the sign of retinal defocus and undergo compensatory growth, the local retinal control of eye growth, regulatory changes in choroidal thickness, and the identification of components in the biochemistry of eye growth leading to the characterization of signal cascades regulating eye growth and refractive state. Several of these findings provided the proofs of concepts that form the scientific basis of new and effective clinical treatments for controlling myopia progression in humans. Experimental animal models continue to provide new insights into the cellular and molecular mechanisms of eye growth control, including the identification of potential new targets for drug development and future treatments needed to stem the increasing prevalence of myopia and the vision-threatening conditions associated with this disease.

The purpose of this study was to evaluate the effect of interrupting negative lens wear for short periods early or late during the development of lens-induced myopia in marmosets. Sixteen marmosets were reared with a −5D contact lens on their right eye (plano on contralateral eye) for 8 weeks. Eight marmosets had lenses removed for 30 mins twice/day during the first four weeks (early interruption) and eight during the last four weeks (late interruption). Data were compared to treated controls that wore lenses continuously (N = 12) and untreated controls (N = 10). Interocular differences (IOD) in vitreous chamber (VC) depth and central and peripheral mean spherical refractive error (MSE) were measured at baseline and after four (T4) and eight (T8) weeks of treatment. Visual experience during the interruptions was monitored by measuring refraction while marmosets were seated at the center of a 1 m radius viewing cylinder. At T4 the eyes that were interrupted early were not different from untreated controls (p = 0.10) and at T8 had grown less and were less myopic than those interrupted later (IOD change from baseline, VC: +0.07 ± 0.04 mm vs +0.20 ± 0.03 mm, p < 0.05; MSE: −1.59 ± 0.26D vs −2.63 ± 0.60D, p = 0.13). Eyes interrupted later were not different from treated controls (MSE, p = 0.99; VC, p = 0.60) and grew at the same rate as during the first four weeks of uninterrupted lens wear (T4 − T0: 3.67 ± 1.1 µm/day, T8 − T4: 3.56 ± 1.3 µm/day p = 0.96). Peripheral refraction was a predictive factor for the amount of myopia developed only when the interruption was not effective. In summary, interrupting hyperopic defocus with short periods of myopic defocus before compensation occurs prevents axial myopia from developing. After myopia develops, interruption is less effective.

With the growing prevalence of myopia, already at epidemic levels in some countries, there is an urgent need for new management approaches. However, with the increasing number of research publications on the topic of myopia control, there is also a clear necessity for agreement and guidance on key issues, including on how myopia should be defined and how interventions, validated by well-conducted clinical trials, should be appropriately and ethically applied. The International Myopia Institute (IMI) reports the critical review and synthesis of the research evidence to date, from animal models, genetics, clinical studies, and randomized controlled trials, by more than 85 multidisciplinary experts in the field, as the basis for the recommendations contained therein. As background to the need for myopia control, the risk factors for myopia onset and progression are reviewed. The seven generated reports are summarized: (1) Defining and Classifying Myopia, (2) Experimental Models of Emmetropization and Myopia, (3) Myopia Genetics, (4) Interventions for Myopia Onset and Progression, (5) Clinical Myopia Control Trials and Instrumentation, (6) Industry Guidelines and Ethical Considerations for Myopia Control, and (7) Clinical Myopia Management Guidelines.

Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

Program Number: 5460 Poster Board Number: B0617 Presentation Time: 8:30 AM–10:15 AM Opposing contributions by D2 receptor activation on form-deprivation myopia development in mice Xiangtian Zhou, Furong Huang, Qiongsi Wang, Lishuai Zhang, Jia Qu. School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China. Purpose: Many studies have shown that retinal dopamine is a major regulator of postnatal eye growth and myopia in animal models. In the present study, we determined the effects of the dopamine D2 receptor agonist, quinpirole, on form-deprivation myopia development (FDM) and whether quinpirole acts at dopamine D2 receptors (D2R) to exert its effect on myopia development using D2R knockout (KO) mice. Methods: Wild-type C57/BL6 (WT) littermates and corresponding D2R KO mice were subjected to FDM at postnatal 28-56 days of age. Both groups were intraperitoneally injected daily with either quinpirole (high dose: 10 mg/kg/day; low dose: 1 mg/kg/day) or vehicle for 4 weeks (starting from postnatal day 28). Their body weight, refraction, corneal radius of curvature and ocular axial components were measured at the end of 4-weeks of treatment. Results: Consistent with our recent report, D2R KO attenuated FDM development compared to WT littermates (-2.29±0.44 D in D2R KO versus -5.23±0.44 D in WT, p<0.05). In the WT mice, the high and low doses of quinpirole had opposite effects on FDM development: high dose promoted myopia development (-8.83±0.72 D in WT-high dose versus -5.23±0.44 D in WT-vehicle, p<0.05) while low dose inhibited it (-1.79±0.35 D in WT-low dose versus -5.23±0.44 D in WT-vehicle, p<0.05). Importantly, these opposing effects of quinpirole on FDM in WT mice were absent in D2R KO mice (D2R KO-high dose or D2R KO-low dose versus D2R KOvehicle, p>0.05). In parallel with refraction changes, these opposing quinpirole effects were accompanied by changes in vitreous chamber depth and axial length that were consistent with those on FDM development. Furthermore, in the D2R KO mice, quinpirole or vehicle treatment did not alter FDM-induced elongation of vitreous chamber depth and increases in axial length. Conclusions: Quinpirole has opposing dose dependent effects on FDM stemming from its interaction with D2R. As D2R is a GPCR coupled to various signaling transduction pathways mediating different responses that may oppose one another, it is conceivable that their activation by this D2 partial agonist is dose dependent. An additional possibility is that quinpirole activates presynaptic D2R autoreceptor-linked signaling, which in turn reduces extracellular space dopamine levels and attenuates dopaminergic signaling. Commercial Relationships: Xiangtian Zhou, None; Furong Huang, None; Qiongsi Wang, None; Lishuai Zhang, None; Jia Qu, None Support: National Natural Science Foundation of China (81422007, 81371047, and 81271039, http://www.nsfc.gov.cn/)