A novel Lenslet-ARray-Integrated spectacle lenses for myopia control: a one-year randomized, double-masked, controlled trial.

PURPOSE: To investigate the myopia control efficacy of novel Lenslet-ARray-Integrated (LARI) spectacle lenses with positive (PLARI) and negative (NLARI) power lenslets worn for one year in myopic children. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: A total of 240 children, aged 6 to 12 years, with spherical equivalent refraction (SER) between -4.00 and -1.00 diopter (D), astigmatism of 1.50 D or less, and anisometropia of 1.00 D or less. METHODS: Participants were assigned randomly in a 1:1:1 ratio to PLARI, NLARI, and a control (single-vision (SV)) groups. Cycloplegic autorefraction and axial length were measured at baseline and 6-month intervals after lens wear. MAIN OUTCOME MEASURES: Changes in SER, axial elongation (AE), and differences between groups. RESULTS: After 1-year, SER changes and AE in the PLARI and NLARI groups were significantly less than those in the SV group (SER: -0.30 ± 0.48 D, -0.21 ± 0.35 D, -0.66 ± 0.40 D; AE: 0.19 ± 0.20 mm, 0.17 ± 0.14 mm, 0.34 ± 0.18 mm, respectively) (all P < 0.001). There were no significant differences in SER changes and AE between PLARI and NLARI groups (P = 0.54 and P = 1.00, respectively). Younger age was associated with more rapid SER increase and larger AE in the SV (r = 0.40, P < 0.001 and r = -0.59, P < 0.001, respectively) and PLARI (r= 0.46, P < 0.001 and r = -0.52, P < 0.001, respectively) groups, but not in the NLARI group (r = -0.002, P = 0.98 and r = -0.08, P = 0.48, respectively). CONCLUSIONS: Compared with the SV group, both PLARI and NARI groups showed significantly slower myopia progression in terms of SER and axial elongation. Faster myopia progression, in terms of both SER and AE, was associated with younger age in the SV and PLARI groups, but not in the NLARI group.

The effects of brief high intensity light on ocular growth in chicks developing myopia vary with time of day.

Evidence suggests that the relevant variable in the anti-myopigenic effect of increased time spent outdoors is the increase in light intensity. Because light is the strongest Zeitgeber, it is plausible that the effects of bright light exposure depend on time of day, and may impact circadian rhythms. In these studies, we asked whether the effects on eye growth rates and ocular rhythms of brief daily exposures to bright light differed depending on time of day in eyes developing myopia in response to form deprivation (FD) or negative lens-induced hyperopic defocus (LENS). We also studied the effects of concurrent exposures to brief hyperopic defocus and bright light. Exp. 1: Starting at 12d, chicks wearing monocular diffusers or -10 D lenses were exposed to 3 daily hours (h) of bright light (30K lux) in the morning (FD: n = 12; LENS: n = 7) or evening (FD: n = 21; LENS: n = 7) for a total of 6 exposures. Controls wore diffusers or lenses but weren't exposed to bright light ("not bright" FD: n = 14; LENS: n = 9). Exp. 2: Untreated chicks were exposed to 3 h bright light in the morning (n = 12) or evening (n = 14) for a total of 6 exposures. Controls were not exposed to bright light (n = 11). Exp. 3: Chicks were exposed to 2 h simultaneous monocular hyperopic defocus and bright light in the morning (n = 11), mid-day (n = 7) or evening (n = 8) for 5 exposures. "Not bright" lens-wearing controls were data from published work (Nickla et al., 2017). High frequency A-scan ultrasonography was done at the start and end to measure growth rates. The FD group in Exp. 1 and the morning and evening groups in Exp. 3 were measured at 6-h intervals over the final 24 h to determine parameters for the rhythms in axial length and choroidal thickness. 1. Brief bright light in the evening inhibited eye growth in eyes wearing diffusers or lenses relative to "not bright" controls(interocular differences: FD: 316 vs 468 µm, p = 0.026; LENS: 233 vs 438 µm, p = 0.03); morning bright light had no effect. There was no differential effect of time of day of exposure on the rhythm in axial length; for choroid thickness, "time" accounted for the variance between groups (2-way ANOVA interaction p = 0.027). 2. In binocularly untreated chicks, bright light in the morning had a small but significant growth stimulatory effect relative to evening exposures (803  vs 679 µm/7d; post-hoc p = 0.048). 3. Eyes exposed to simultaneous hyperopic defocus and bright light were significantly more inhibited relative to "not bright" controls for morning exposures (interocular differences: -207 vs 69 µm; p < 0.01). In conclusion, the effects of brief periods of bright light on the growth controller depended on the time of day of exposure and on the contemporaneous state ofocular growth .

Global-flash mfERG responses to local differences in spherical and astigmatic defocus across the human retina.

PURPOSE: Emmetropisation is essentially a visually guided, within-eye process. We investigated differences in global-flash multifocal electroretinogram (gmfERG) responses to naturally occurring differences in spherical and astigmatic defocus across the retina, which might provide a basis for guiding eye growth. METHODS: Experiment 1: The gmfERG responses (direct, DC, and induced, IC, amplitudes and latencies) recorded simultaneously from six retinal areas (15° eccentricity, spaced at 60°, areas 3.2°2 ) were correlated with the uncorrected retinal defocus measured at the six corresponding retinal locations in 20 adults with foveal refractive errors (-4.75 to +1.25D). No correcting lenses were used to avoid introduction of lens-induced aberrations and magnification. Experiment 2 investigated the effect of superimposing astigmatic defocus (+2.00/-4.00D Jackson Cross Cylinder presented at four orientations) on gmfERG responses. RESULTS: Experiment 1: DC and IC response amplitudes were greater in retinal regions naturally exposed to more hyperopic spherical defocus (DC: rho = 0.26, p = 0.005; IC: rho = 0.29, p = 0.001), but response latencies were unaffected by sign or magnitude of spherical defocus (DC: p = 0.34; IC: p = 0.40). Response amplitudes and latencies were unaffected by astigmatic defocus. Experiment 2: Rotating the JCC axis to four different orientations had no effect on the gmfERG responses (DC amplitude, p = 0.39; DC latency, p = 0.10; IC amplitude, p = 0.51; IC latency, p = 0.64). CONCLUSION: The gmfERG responses from discrete retinal areas varied with the sign and magnitude of local spherical defocus, but we found no evidence that retinal responses were affected by astigmatic defocus. Therefore, local astigmatism is unlikely to provide cues for controlling eye growth, whereas differences in response to spherical defocus between different retinal regions could potentially provide cues for controlling eye growth in emmetropisation.

Influence of the time of day on axial length and choroidal thickness changes to hyperopic and myopic defocus in human eyes.

Research in animal models have shown that exposing the eye to positive or negative spectacle lenses can lead to predictable changes in eye growth. Recent research indicates that brief periods (1-2 h) of monocular defocus results in small, but significant changes in axial length and choroidal thickness of human subjects. However, the effects of the time of day on these ocular changes with defocus are not known. In this study, we examined the effects of monocular myopic and hyperopic defocus on axial length and choroidal thickness when applied in the morning (change between 10 a.m. and 12 p.m.) vs the evening (change between 5 and 7 p.m.) in young adult human participants (mean age, 23.44 ±â€¯4.52 years). A series of axial length (using an IOL Master) and choroidal thickness (using an optical coherence tomographer) measurements were obtained over three consecutive days in both eyes. Day 1 (no defocus) examined the baseline ocular measurements in the morning (10 a.m. and 12 p.m.) and in the evening (5 and 7 p.m.), day 2 investigated the effects of hyperopic and myopic defocus on ocular parameters in the morning (subjects wore a spectacle lens with +3 or -3 DS over the right eye and a plano lens over the left eye between 10 a.m. and 12 p.m.), and day 3 examined the effects of defocus in the evening (+3 or -3 DS spectacle lens over the right eye between 5 and 7 p.m.). Exposure to myopic defocus caused a significant reduction in axial length and thickening of the subfoveal choroid at both times; but, compared to baseline data from day 1, the relative change in axial length (-0.021 ± 0.009 vs +0.004 ± 0.003 mm, p = 0.009) and choroidal thickness (+0.027 ± 0.006 vs +0.007 ± 0.006 mm, p = 0.011) with defocus were significantly greater for evening exposure to defocus than for the morning session. On the contrary, introduction of hyperopic defocus resulted in a significant increase in axial length when given in the morning (+0.026 ± 0.006 mm), but not in the evening (+0.001 ± 0.003 mm) (p = 0.047). Furthermore, hyperopic defocus resulted in a significant thinning of the choroid (p = 0.005), but there was no significant influence of the time of day on choroidal changes associated with hyperopic defocus (p = 0.672). Exposure to hyperopic and myopic defocus at different times of the day was also associated with changes in the parafoveal regions of the choroid (measured across 1.5 mm nasal and temporal choroidal regions on either side of the fovea). Our results show that ocular response to optical defocus varies significantly depending on the time of day in human subjects. These findings represent a potential interaction between the signal associated with the eye's natural diurnal rhythm and the visual signal associated with the optical defocus, making the eye perhaps more responsive to hyperopic defocus (or 'go' signal) in the morning, and to myopic defocus (or 'stop' signal) in the latter half of the day.

Relationship between peripheral refraction, axial lengths and parental myopia of young adult myopes.

PURPOSE: To determine the relationship between peripheral refraction at the horizontal retina, axial length and parental history of myopia between myopic adults who have positive parental myopia and those with negative parental myopia. METHODS: 69 males and 44 females in the age range of 18-25 years were assigned either a negative parental myopia (NPM) or positive parental myopia (PPM) group. In the corrected and uncorrected states, peripheral refractive error was measured up to 30° horizontally in 10° steps using an open field autorefractor. Axial length was measured using an Opto US1000 Fine A-Scan Ultrasonography (model US1000). RESULTS: Relative peripheral refractive error showed more hyperopic defocus that was statistically significantly more increased in the positive parental myopia group than in the negative parental myopia group (P ≥ 0.02). The overall mean ± SD axial length of all subjects was 23.38 ± 0.32 mm (range 23.01-25.01 mm). The study showed a statistically significant difference (P = 0.005) in axial lengths of young adult myopes (23.45 ± 0.36 mm) with parental myopia compared to those with similar spherical equivalent refraction who have non-myopic parents (23.28 ± 0.19 mm). CONCLUSION: There was significantly more hyperopic defocus at 30° N and 30° T retina in the corrected states of young adult myopes who had myopic parents compared to their counterparts with non-myopic parents.

Novel application of multispectral refraction topography in the observation of myopic control effect by orthokeratology lens in adolescents.

BACKGROUND: Myopia, as one of the common ocular diseases, often occurs in adolescence. In addition to the harm from itself, it may also lead to serious complications. Thus, prevention and control of myopia are attracting more and more attention. Previous research revealed that single-focal glasses and orthokeratology lenses (OK lenses) played an important part in slowing down myopia and preventing high myopia. AIM: To compare the clinical effects of OK lenses and frame glasses against the increase of diopter in adolescent myopia and further explore the mechanism of the OK lens. METHODS: Changes in diopter and axial length were collected among 70 adolescent myopia patients (124 eyes) wearing OK lenses for 1 year (group A) and 59 adolescent myopia patients (113 eyes) wearing frame glasses (group B). Refractive states of their retina were inspected through multispectral refraction topography. The obtained hyperopic defocus was analyzed for the mechanism of OK lenses on slowing down the increase of myopic diopter by delaying the increase of ocular axis length and reducing the near hyperopia defocus. RESULTS: Teenagers in groups A and B were divided into low myopia (0D - -3.00 D) and moderate myopia (-3.25D - -6.00 D), without statistical differences among gender and age. After 1-year treatment, the increase of diopter and axis length and changes of retinal hyperopic defocus amount of group A were significantly less than those of group B. According to the multiple linear analysis, the retinal defocus in the upper, lower, nasal, and temporal directions had almost the same effect on the total defocus. The amount of peripheral retinal defocus (15°-53°) in group A was significantly lower than that in group B. CONCLUSION: Multispectral refraction topography is progressive and instructive in clinical prevention and control of myopia.

Inverting peripheral hyperopic defocus into myopic defocus among myopic schoolchildren using addition power of multifocal contact lens.

PURPOSE: The purpose was to determine the minimum near-addition power needed using Proclear® multifocal D-Design contact lens (adds: +1.50 D, +2.50 D, +3.00 D, and +3.50 D) to invert the pattern of relative hyperopic defocus in the peripheral retina into relative myopic defocus among the eyes of myopic schoolchildren. METHODS: Twenty-seven right eyes (24 females and 3 males) of 27 myopic schoolchildren aged between 13 and 15 years were included in this study. The measurements of central refraction, peripheral refraction (between 35° temporal and 35° nasal visual field in 5° steps), and lag of accommodation were conducted using the Grand-Seiko WR-5100K open-field autorefractometer initially without correction (WC), followed by with correction using four different addition powers of Proclear® multifocal D-Design contact lens in random sequence. Axial length was measured using a handheld probe ultrasound A-scan (Tomey AL-2000). RESULTS: The relative peripheral refractive error showed high hyperopic defocus of +1.08 ± 1.24 D at 35° nasal and +1.06 ± 1.06 D at 35° temporal visual field WC. All Proclear multifocal contact lenses (MFCLs) decreased the peripheral hyperopic defocus with increasing addition powers (F [2.938, 47.001] = 13.317, P < 0.001). However, only +3.00 D addition and +3.50 D addition (P = 0.001) could invert the peripheral hyperopic defocus into peripheral myopic defocus. Apart from that, the +3.00 D addition lens showed the lowest lag of accommodation (+1.10 ± 0.83 D) among the other MFCL adds (P = 0.002). CONCLUSION: A +3.00 D addition Proclear MFCL is the optimal addition power that can invert the pattern of peripheral hyperopic defocus into myopic defocus.

Effect of spectacle lenses designed to reduce relative peripheral hyperopia on myopia progression in Japanese children: a 2-year multicenter randomized controlled trial.

PURPOSE: Novel spectacle lenses (MyoVision, Carl Zeiss) designed to reduce relative peripheral hyperopia have been developed and reported to be effective for preventing myopia progression in a subgroup of Chinese children. In this study we examined the efficacy of MyoVision lenses in Japanese children. STUDY DESIGN: This was a multicenter prospective randomized double-blind placebo-controlled trial. METHOD: We enrolled 207 participants (aged 6-12 years) with spherical equivalent refractions (SERs) ranging from -1.5 to -4.5 diopters (D) and with at least 1 myopic parent. The participants were randomized to receive either single vision lenses (SVLs) or MyoVision lenses and were followed up every 6 months for 2 years. The primary outcome was myopia progression evaluated by cycloplegic autorefraction, and the secondary outcome was elongation of axial length. RESULTS: A total of 203 children (98.1%) completed the follow-up. The mean adjusted change in SER was -1.43 ± 0.10 D in the MyoVision group, which was not significantly different from that of the control group wearing SVLs (-1.39 ± 0.07 D) at the 24-month visit (P = .65). The adjusted axial length elongation was 0.73 ± 0.04 mm in the MyoVision group, which was not significantly different from that in the control group wearing SVLs (0.69 ± 0.03 mm) at the 24-month visit (P = .28). CONCLUSION: The results of this clinical trial could not verify the therapeutic effect of MyoVision for slowing down myopia progression in Japanese children. Additional studies are needed to design lenses that can reduce peripheral hyperopic defocus individually and to examine the effectiveness of these lenses in preventing myopia progression.

Effect of Peripheral Defocus on Axial Eye Growth and Modulation of Refractive Error in Hyperopes: Protocol for a Nonrandomized Clinical Trial.

BACKGROUND: Hyperopia occurs due to insufficient ocular growth and a failure to emmetropize in childhood. In anisohyperopia, it is unclear why one eye may remain hyperopic while the fellow eye grows toward an emmetropic state. Animal studies have shown that manipulating peripheral defocus through optical means while simultaneously providing correct axial focus can either discourage or encourage axial eye growth to effectively treat myopia or hyperopia, respectively. Myopia progression and axial eye growth can be significantly reduced in children and adolescents through the use of multifocal contact lenses. These contact lenses correct distance central myopia while simultaneously imposing relative peripheral myopic defocus. The effect of correcting distance central hyperopia while simultaneously imposing relative peripheral hyperopic defocus is yet to be elucidated in humans. OBJECTIVE: The objective of our study is to understand the natural progression of axial eye growth and refractive error in hyperopes and anisohyperopes and to establish whether axial eye growth and refractive error can be modified using multifocal contact lenses in hyperopes and anisohyperopes. METHODS: There are 3 elements to the program of research. First, the natural progression of axial eye growth and refractive error will be measured in spectacle-wearing hyperopic and anisohyperopic subjects aged between 5 and <20 years. In other words, the natural growth of the eye will be followed without any intervention. Second, as a paired-eye control study, anisohyperopes aged between 8 and <16 years will be fitted with a center-near multifocal design contact lens in their more hyperopic eye and a single-vision contact lens in the fellow eye if required. The progression of axial eye growth and refractive error will be measured and compared. Third, subjects aged between 8 and <16 years with similar levels of hyperopia in each eye will be fitted with center-near multifocal design contact lenses in each eye; the progression of axial eye growth and refractive error in these subjects will be measured and compared with those of subjects in the natural progression study. RESULTS: Recruitment commenced on 6 June 2016 and was completed on 8 April 2017. We estimate the data collection to be completed by April 2020. CONCLUSIONS: This trial will establish whether axial eye growth can be accelerated in children with hyperopia by imposing relative peripheral hyperopic defocus using center-near multifocal contact lenses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02686879; https://clinicaltrials.gov/ct2/show/NCT02686879 (Archived by Webcite at http://www.webcitation.org/71o5p3fD2). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9320.

Peripheral refraction with different designs of progressive soft contact lenses in myopes.

Aim: The purpose of this study was to compare the changes in relative peripheral refractive error produced by two different designs of progressive soft contact lenses in myopic schoolchildren. Methods: Twenty-seven myopic schoolchildren age between 13 to 15 years were included in this study. The measurements of central and peripheral refraction were made using a Grand-Seiko WR-5100K open-field autorefractometer without correction (baseline), and two different designs of progressive contact lenses (PCLs) (Multistage from SEED & Proclear from Cooper Vision) with an addition power of +1.50 D. Refractive power was measured at center and at eccentricities between 35º temporal to 35º nasal visual field (in 5º steps). Results: Both PCLs showed a reduction in hyperopic defocus at periphery. However, this reduction was only significant for the Multistage PCL (p= 0.015), (Proclear PCL p= 0.830).  Conclusion: Multistage PCLs showed greater reduction in peripheral retinal hyperopic defocus among myopic schoolchildren in comparison to Proclear PCLs.