IMI 2023 Digest.

Myopia is a dynamic and rapidly moving field, with ongoing research providing a better understanding of the etiology leading to novel myopia control strategies. In 2019, the International Myopia Institute (IMI) assembled and published a series of white papers across relevant topics and updated the evidence with a digest in 2021. Here, we summarize findings across key topics from the previous 2 years. Studies in animal models have continued to explore how wavelength and intensity of light influence eye growth and have examined new pharmacologic agents and scleral cross-linking as potential strategies for slowing myopia. In children, the term premyopia is gaining interest with increased attention to early implementation of myopia control. Most studies use the IMI definitions of ≤-0.5 diopters (D) for myopia and ≤-6.0 D for high myopia, although categorization and definitions for structural consequences of high myopia remain an issue. Clinical trials have demonstrated that newer spectacle lens designs incorporating multiple segments, lenslets, or diffusion optics exhibit good efficacy. Clinical considerations and factors influencing efficacy for soft multifocal contact lenses and orthokeratology are discussed. Topical atropine remains the only widely accessible pharmacologic treatment. Rebound observed with higher concentration of atropine is not evident with lower concentrations or optical interventions. Overall, myopia control treatments show little adverse effect on visual function and appear generally safe, with longer wear times and combination therapies maximizing outcomes. An emerging category of light-based therapies for children requires comprehensive safety data to enable risk versus benefit analysis. Given the success of myopia control strategies, the ethics of including a control arm in clinical trials is heavily debated. IMI recommendations for clinical trial protocols are discussed.

The effect of concentric and aspheric multifocal soft contact lenses on binocular vision in young adult myopes.

PURPOSE: Multifocal soft contact lenses (MFCLs) are prescribed to inhibit myopia progression; these include aspheric and concentric designs. The effects of MFCLs on visual quality, accommodation and vergence in young-adult myopes were evaluated. METHODS: Participants were twenty-six myopes (19-25 years, spherical equivalent -0.50 to -5.75D), with normal binocular vision and no past myopia control. Pupil sizes were 4.4 ± 0.9 mm during distance viewing and 3.7 ± 0.8 mm at near. In random order, participants wore four MFCLs: Proclear single vision distance, MiSight concentric dual focus (+2.00D), distance center aspheric (Biofinity, +2.50D) (CooperVision lenses), and NaturalVue aspheric (Visioneering Technologies). Testing included visual acuity, contrast sensitivity (Pelli-Robson), stereoacuity, accommodation response, negative and positive relative accommodation, horizontal phorias, horizontal fusional vergence and AC/A ratio, and a visual quality questionnaire. RESULTS: The four lenses differed in distance (p = 0.001) and near visual acuity (p = 0.011), and contrast sensitivity (p = 0.001). Compared with the single vision lens, the Biofinity aspheric had the greatest visual impact: 0.19 ± 0.14 logMAR distance acuity reduction, 0.22 ± 0.15 log contrast sensitivity reduction. Near acuity was affected less than distance acuity; the reduction was greatest with the NaturalVue (0.05 ± 0.07 logMAR reduction). The MFCLs altered the autorefraction measure at distance and near (p = 0.001); the accommodation response was less with aspheric lenses. Negative relative accommodation reduced with the aspheric lenses (p = 0.001): by 0.9 ± 0.5D with Biofinity and 0.5 ± 0.7D with NaturalVue. Exophoric shifts were greater with aspheric lenses (1.8 ± 2.4Δ Biofinity, 1.7 ± 1.7Δ NaturalVue) than with the concentric MiSight (0.5 ± 1.3Δ). CONCLUSIONS: MFCLs alter visual performance, refraction and vergence; two aspheric lenses had greater effect than a concentric lens.

Multifocal contact lens design, not addition power, affects accommodation responses in young adult myopes.

PURPOSE: Prolonged nearwork has been implicated in myopia progression. Accommodation responses of young-adult myopes wearing different multifocal contact lenses were compared. METHODS: Twenty adults, 18-25 years, with myopia (spherical equivalent refraction -0.50 to -5.50 D, mean -2.1 ± 1.6 D) wore five lens types in random order: Proclear single vision distance (SV), MiSight concentric dual-focus +2.00 D Add (MS), Biofinity aspheric centre distance +1.50 D Add (CD1) and +2.50 D Add (CD2) (all Coopervision), and NaturalVue aspheric (Visioneering Technologies) (NVue). Using a Grand-Seiko WAN-5500 autorefractor with binocular correction and viewing right eye accommodative responses were measured after a 10 min adaptation period at 4.0, 1.0, 0.5, 0.33 and 0.25 m distances. Dynamic measurements were taken for 4 s at 6 Hz. Accommodative stimuli and responses were referenced to 4 m (i.e., refraction differences between 4 m and nearer distances). Accommodation lags and refraction instabilities (standard deviations of dynamic responses) were determined. For comparison, results were obtained for an absolute presbyopic eye, where trial lenses counteracted the accommodation stimulus. RESULTS: For SV and MS, accommodation responses were similar to the stimulus values. For aspheric lenses CD1, CD2 and NVue, accommodation responses were approximately 1.0 D lower across the stimulus range than with SV and MS, and rates of change were approximately 0.84 D per 1 D stimulus change. MS produced greater refraction instabilities than other lenses. For the presbyope, changes in refraction matched the trial lenses, indicating that corrections due to measurement through the different lenses were not needed. CONCLUSION: Reductions in accommodation response occurred in young myopes wearing aspheric multifocal contact lenses independent of the labelled 'add' power. The concentric dual-focus MS lens produced minimal lags but had greater instability than the other lenses. The results indicate that the mechanism of multifocal contact lenses slowing myopia progression is unlikely to be through relaxing accommodation, at least in young adults.

IMI 2021 Yearly Digest.

Purpose: The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers. Methods: A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered. Results: One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologic myopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss. Conclusions: Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.

CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye.

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia). However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation. In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

Zone of Clear Single Binocular Vision in Myopic Orthokeratology.

PURPOSE: To examine the zone of clear single binocular vision (ZCSBV) in myopic children and young adults after 12 months of orthokeratology (OK) wear, in comparison with single-vision soft contact lens (SCL) wear. METHODS: Twelve children (8-16 years) and 8 adults (18-29 years) were assessed with a series of near-point binocular vision tests when myopia was corrected using single-vision SCLs and again after 1 and 12 months of OK wear, and axial length was measured. The ZCSBV was constructed for baseline SCL wear and after 12 months of OK wear. RESULTS: After 1 month of OK wear, increased accommodative responses were noted in children (C) and adults (A) as increased binocular amplitude (C:P=0.03, A:P=0.04) and reduced accommodative lag (C:P=0.01, A:P=0.01). Divergence reserves improved after 1 month in both groups (P<0.04), and a near exophoric shift was evident at 12 months (C:P=0.01, A:P=0.04). All changes at 1 month maintained stability at 12 months. An increase in accommodation and vergence responses without reduction in range resulted in an expansion of the ZCSBV in both age groups. Axial length did not significantly change in either children (P=0.25) or adults (P=0.72). CONCLUSION: In both pediatric and young adult myopes, the ZCSBV expands toward a more divergent, increased accommodation response in OK compared with SCL wear. This occurs without a corresponding loss of convergence or accommodation deactivation, indicating improved depth of focus. These findings are relevant to visual acceptance and possible mechanisms of OK's efficacy for myopia control.

Stability of peripheral refraction changes in orthokeratology for myopia.

PURPOSE: Orthokeratology (OK) is known to alter relative peripheral refraction (RPR) with this presumed to be its key myopia control mechanism. A prospective, longitudinal study was performed to examine stability of OK-induced RPR changes in myopic children and young adults. METHODS: RPR of twelve children (C)(8-16 years) and eight adults (A)(18-29 years) with spherical equivalent refraction of -0.75 to -5.00D were measured unaided and while wearing single vision soft contact lenses (SCL). Measurements were repeated after 1, 6 and 12 months of OK wear. RPR was measured using an open-field Shin Nippon SRW-5000 autorefractor at 10, 20 and 30 degrees nasally (N) and temporally (T), converted into power vectors M, J0 and J45. On-axis refractions and axial lengths (IOL Master) were also measured. RESULTS: Compared to the unaided state, 1-month of OK wear shifted the RPR in the myopic direction at 30 T (C: p = 0.023; A:, p = 0.002) and 30 N (C&A, p = 0.003) and was stable thereafter, with similar changes compared to SCL wear. J0 showed a myopic shift in comparison to both unaided and SCL correction in children but not adults, and J45 did not change in either group. The on-axis OK correction was predictive of the RPR shift in both children and adults at 30 T (C: r=-0.58, p = 0.029; A: r=-0.92, p < 0.001) and 30 N (C: r=-0.60, p = 0.024; A: r=-0.74, p = 0.013) with symmetry of RPR shifts (C: r = 0.67, p = 0.008; A: r = 0.85, p = 0.004). No relationships between changes in RPR and axial length were found after twelve months of OK wear; level of myopia was stable in both groups. CONCLUSION: Relative to both unaided and single vision SCL correction, OK shifted the RPR in the myopic direction; the RPR was stable from 1 to 12 months. The RPR shift in OK wear varied with the degree of myopia but was not correlated with myopia progression.

Childhood and lifetime risk comparison of myopia control with contact lenses.

PURPOSE: The relative risks of ocular pathology with increasing myopia have been described; the absolute lifetime risk of vision impairment from myopia is yet to be compared to the childhood and lifetime risks of contact lens wear for myopia control. METHODS: Using peer-reviewed data, the absolute risks of microbial keratitis (MK) in daily disposable soft, reusable soft and orthokeratology contact lens (CL) wear were calculated over both a childhood (age 8-18) and a lifetime (age 8-65) of CL wear. This was compared to the previously published cumulative risk of vision impairment by age 75 based on increasing myopia and axial length. Data were converted utilizing the Council of International Organizations of Medical Sciences (CIOMS) classification system for frequency of adverse events, with 95 % confidence intervals included. RESULTS: The lifetime risk of vision impairment in axial lengths over 26 mm and more than 6D of myopia is greater than the lifetime risk of MK in any CL modality, except for adult SCL extended wear. If axial length is below 26 mm and myopia lower than 3D, a lifetime of CL wear is more risky in comparison, except in the case of daily disposable wear. Ten years of childhood CL wear of any modality presents lower likelihood of MK than any comparable risk of vision impairment. CONCLUSION: The comparative lifetime risks of contact lens wear commenced at age 8 for myopia control are less than the lifetime risks of vision impairment with myopia more than 6D or axial length more than 26 mm. When only childhood CL wear is considered, the risk comparison is clearly skewed towards the positive impact of CL wear, especially in daily disposable wear. Clinicians should be confident to proactively recommend myopia control CL wear to younger children, as both the safety profile and potential preventative ocular health benefits are evident.

Effects of eye rotation and contact lens decentration on horizontal peripheral refraction.

PURPOSE: Peripheral refraction is important in design of myopia control therapies. The aim was to investigate the influence of contact lens decentration associated with eye rotation on peripheral refraction in the horizontal visual field. METHODS: Participants were 10 emmetropes and 10 myopes in good general and ocular health. Right eyes underwent cycloplegic peripheral refraction, using a Grand-Seiko WAM-5500 Autorefractor, in 5° steps to ±35° eccentricities along the horizontal visual field. Targets were fixated using eye rotation only or head rotation only. Refractions were measured without correction and with three types of contact lenses: single vision, a multifocal centre-distance aspheric with +2.50 D add and NaturalVue aspheric. Photographs of eyes during lens wear were taken for each eye rotation. Effects of visual field angle, lens type and test method (head or eye rotation) on vector components of relative peripheral refraction were evaluated using repeated measures anovas. Test method for each visual field angle/lens combination were compared via paired t-tests. RESULTS: Horizontal decentration ranges across the visual field were 1.2 ± 0.6 mm for single vision and 1.2 ± 0.4 mm for multifocal lenses but smaller at 0.7 ± 0.4 mm for NaturalVue lenses. There were only two significant effects of test method across the visual field angle/lens type combinations (single vision: for emmetropes horizontal/vertical astigmatism component at 35° nasal with mean difference -0.38 D and for myopes spherical equivalent refraction at 20° temporal with mean difference +0.24 D). CONCLUSION: Upon eye rotation the contact lenses decentred on the eye, but not enough to affect peripheral refraction. For the types assessed and for the horizontal visual field out to ±35° when measurements were performed with the Grand-Seiko WAM-5500 autorefractor, it is valid to use eye rotations to investigate peripheral refraction.

IMI - Myopia Control Reports Overview and Introduction.

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.

IMI - Industry Guidelines and Ethical Considerations for Myopia Control Report.

Purpose: To discuss guidelines and ethical considerations associated with the development and prescription of treatments intended for myopia control (MC). Methods: Critical review of published papers and guidance documents was undertaken, with a view to carefully considering the ethical standards associated with the investigation, development, registration, marketing, prescription, and use of MC treatments. Results: The roles and responsibilities of regulatory bodies, manufacturers, academics, eye care practitioners, and patients in the use of MC treatments are explored. Particular attention is given to the ethical considerations for deciding whether to implement a MC strategy and how to implement this within a clinical trial or practice setting. Finally, the responsibilities in marketing, support, and education required to transfer required knowledge and skills to eye care practitioners and academics are discussed. Conclusions: Undertaking MC treatment in minors creates an ethical challenge for a wide variety of stakeholders. Regulatory bodies, manufacturers, academics, and clinicians all share an ethical responsibility to ensure that the products used for MC are safe and efficacious and that patients understand the benefits and potential risks of such products. This International Myopia Institute report highlights these ethical challenges and provides stakeholders with recommendations and guidelines in the development, financial support, prescribing, and advertising of such treatments.

IMI - Clinical Management Guidelines Report.

Best practice clinical guidelines for myopia control involve an understanding of the epidemiology of myopia, risk factors, visual environment interventions, and optical and pharmacologic treatments, as well as skills to translate the risks and benefits of a given myopia control treatment into lay language for both the patient and their parent or caregiver. This report details evidence-based best practice management of the pre-, stable, and the progressing myope, including risk factor identification, examination, selection of treatment strategies, and guidelines for ongoing management. Practitioner considerations such as informed consent, prescribing off-label treatment, and guides for patient and parent communication are detailed. The future research directions of myopia interventions and treatments are discussed, along with the provision of clinical references, resources, and recommendations for continuing professional education in this growing area of clinical practice.