Human Myopia Research Articles

Flicker downregulates the content of crystallin proteins in form-deprived C57BL/6 mouse retina

Image degradation by loss of higher spatial frequencies causes form-deprivation myopia (FDM) in humans and animals, and cyclical illumination (flicker) at certain frequencies may prevent FDM. The molecular mechanisms underlying FDM and its prevention by flicker are poorly known. To understand them better, we have identified proteins that differ in amount in form-deprived (FD) mouse retinas, under steady versus flickering light. Male C57BL/6 mice (age 27–29 days) were randomly divided into three groups: Experimental – monocularly form-deprived, and kept under either normal room light (“FD-Only”) or 20 Hz flickering light (“FD-Flicker”), throughout the 12-hour light phase; and Control (“Open-Control”) – kept under normal illumination, without form deprivation. After two weeks of treatment, retinal proteins were extracted and separated by two-dimensional gel electrophoresis (2D-GE); proteins that differ in content in FD-only versus FD-flicker retinas were identified by mass spectroscopy (“MS”), and their identities were verified by western blotting. The contents of three identified proteins differed statistically in FD-only compared to FD-flicker retinas. These proteins were identified by MS as α-A-crystallin, crystallin β A2 and crystallin β A1. Quantitative western blotting showed that the relative amount of α-A-crystallin in FD-only retinas was significantly higher than that in FD-Flicker and control retinas. In conclusion, form deprivation induced significant increases in the amounts of crystallins in mouse retinas. These increases were significantly reduced by exposure to 20 Hz flicker. Since form deprivation is known to induce myopia development, and flicker to prevent it, our data suggest that FD- and flicker-responsive changes in the content of crystallin proteins may be involved causally or protectively in myopia development.

Relative size of the eye and orbit: An evolutionary and craniofacial constraint model for examining the etiology and disparate incidence of juvenile-onset myopia in humans

The principal aim of this research is to provide a new model for investigating myopia in humans, and contribute to an understanding of the degree to which modern variation and evolutionary change in orbital and overall craniofacial morphology may help explain the common eye form association with this condition. Recent research into long and short-term evolution of the human orbit reveals a number of changes in this feature, and particularly since the Upper Paleolithic. These include a reduction in orbital depth, a decrease in anterior projection of the upper and lower orbital margins, and most notably, a reduction in orbital volume since the Holocene in East Asia. Reduced orbital volume in this geographic region could exacerbate an existing trend in recent hominin evolution toward larger eyes in smaller orbits, and may help explain the unusually high frequency of myopia in East Asian populations. The objective of the current study is to test a null hypothesis of no relationship between a ratio of orbit to eye volume and spherical equivalent refractive error (SER) in a sample of Chinese adults, and examine how relative size of the eye within the orbit relates to SER between the sexes and across the sample population.Analysis of the orbit, eye, and SER reveals a strong relationship between relative size of the eye within the orbit and the severity of myopic refractive error. An orbit/eye ratio of 3 for females and 3.5 for males (or an eye that occupies approximately 34% and 29% of the orbit, respectively), designates a clear threshold at which myopia develops, and becomes progressively worse as the eye continues to occupy a greater proportion of the orbital cavity. These results indicate that relative size of the eye within the orbit is an important factor in the development of myopia, and suggests that individuals with large eyes in small orbits lack space for adequate development of ocular tissues, leading to compression and distortion of the lithesome globe within the confines of the orbital walls. The results of this study indicate that future research examining the etiology of juvenile-onset myopia, and particularly its correlation with ancestry, sex, age, and intelligence, should consider how the eye interacts with the matrix of structural and functional components of the skull during both ontogenetic and evolutionary morphogenesis.

Comparison of two scanning instruments to measure peripheral refraction in the human eye

To better understand how peripheral refraction affects development of myopia in humans, specialized instruments are fundamental for precise and rapid measurements of refraction over the visual field. We compare here two prototype instruments that measure in a few seconds the peripheral refraction in the eye with high angular resolution over a range of about ±45 deg. One instrument is based on the continuous recording of Hartmann-Shack (HS) images (HS scanner) and the other is based on the photorefraction (PR) principle (PR scanner). On average, good correlations were found between the refraction results provided by the two devices, although it varied across subjects. A detailed statistical analysis of the differences between both instruments was performed based on measurements in 35 young subjects. Both instruments have advantages and disadvantages. The HS scanner also provides the high-order aberration data, while the PR scanner is more compact and has a lower cost. Both instruments are current prototypes, and further optimization is possible to make them even more suitable tools for future visual optics and myopia research and also for different ophthalmic applications.

The Effect of Two-Zone Concentric Bifocal Spectacle Lenses on Refractive Error Development and Eye Growth in Young Chicks

To characterize the effects on refractive error development and eye growth in young chicks of two-zone concentric lens designs, which differentially affect the defocus experiences of central and peripheral retinal regions. Monocular defocusing lenses were worn for 5 days from 17 days of age. Four two-zone concentric lens designs (overall optical zone diameter, 10 mm) combining plano with either -5- or +5-D power were used. Lens designs were as follows: (1) +5 D center (+5C), (2) +5 D periphery (+5P), (3) -5 D center (-5C), and (4) -5 D peripheral (-5P), with plano in periphery for all C-designs and in the center for P-designs. Five central zone diameters (CZDs) were tested, ranging from 2.5 to 6.5 mm in 1-mm increments. Plano, +5- and -5-D single-vision (SV) lenses were used as the control. A minimum of six birds were included in each lens group. For the two-zone lenses, the P designs (i.e., peripheral defocus) had greater effects than the C designs (i.e., central defocus) on both on-axis eye growth and refractions. All but the 6.5-mm CZD +5P lens induced larger changes than the +5SV lens. The +5C lenses with CZD less than 5.5 mm had little effect. The two-zone -5-D lenses had less effect than the -5SV lens, and only the 6.5-mm CZD lens of the -5C series had a significant effect. The results demonstrate that peripheral defocus can influence both peripheral and central refractive development. The inhibitory effect on axial eye growth of the +5P lenses opens the possibility that appropriately designed concentric lenses may control the progression of human myopia.

Ocular Components in Three Breeds of Dogs with High Prevalence of Myopia

Experimental models of human myopia have been developed using animals of various species. However, most of these are an induced rather than a spontaneous, naturally occurring myopia. This study was conducted to evaluate whether the spontaneous myopia found in three canine breeds was axial in nature and therefore similar to humans. Refractive error was measured by cycloplegic retinoscopy and ocular components by A-scan ultrasound (ocular axial dimensions) and videophakometry (corneal and lens radii and powers) in 83 dogs of three breeds [English Springer Spaniels (n = 33), Toy Poodles (n = 36), and Collies (n = 14)]. Dogs with refractive errors equal to or more myopic than -0.5 diopters spherical equivalent were considered myopic. Myopia was most common in Toy Poodles (63.9%), followed by English Springer Spaniels (36.4%) and Collies (35.7%). Axial lengths and vitreous chamber depths were not different between myopic and non-myopic dogs (p = 0.84 and 0.63, respectively). The anterior crystalline lens radius was steeper and the lens power was greater in myopic compared with non-myopic dogs (p = 0.048 for each). Spontaneous myopia was very common in all three breeds in this sample of dogs, with Toy Poodles being most affected. However, the cause of the myopia appeared to be refractive, that is from a steeper, more powerful crystalline lens, rather than from excess axial elongation. These breeds do not appear to be promising models for human axial myopia.

Nature and nurture: the complex genetics of myopia and refractive error

The refractive errors, myopia and hyperopia, are optical defects of the visual system that can cause blurred vision. Uncorrected refractive errors are the most common causes of visual impairment worldwide. It is estimated that 2.5 billion people will be affected by myopia alone within the next decade. Experimental, epidemiological and clinical research has shown that refractive development is influenced by both environmental and genetic factors. Animal models have showed that eye growth and refractive maturation during infancy are tightly regulated by visually guided mechanisms. Observational data in human populations provide compelling evidence that environmental influences and individual behavioral factors play crucial roles in myopia susceptibility. Nevertheless, the majority of the variance of refractive error within populations is thought to be because of hereditary factors. Genetic linkage studies have mapped two dozen loci, while association studies have implicated more than 25 different genes in refractive variation. Many of these genes are involved in common biological pathways known to mediate extracellular matrix (ECM) composition and regulate connective tissue remodeling. Other associated genomic regions suggest novel mechanisms in the etiology of human myopia, such as mitochondrial-mediated cell death or photoreceptor-mediated visual signal transmission. Taken together, observational and experimental studies have revealed the complex nature of human refractive variation, which likely involves variants in several genes and functional pathways. Multiway interactions between genes and/or environmental factors may also be important in determining individual risks of myopia, and may help explain the complex pattern of refractive error in human populations.

Knockdown of Zebrafish Lumican Gene (zlum) Causes Scleral Thinning and Increased Size of Scleral Coats

The lumican gene (lum), which encodes one of the major keratan sulfate proteoglycans (KSPGs) in the vertebrate cornea and sclera, has been linked to axial myopia in humans. In this study, we chose zebrafish (Danio rerio) as an animal model to elucidate the role of lumican in the development of axial myopia. The zebrafish lumican gene (zlum) spans approximately 4.6 kb of the zebrafish genome. Like human (hLUM) and mouse (mlum), zlum consists of three exons, two introns, and a TATA box-less promoter at the 5'-flanking region of the transcription initiation site. Sequence analysis of the cDNA predicts that zLum encodes 344 amino acids. zLum shares 51% amino acid sequence identity with human lumican. Similar to hLUM and mlum, zlum mRNA is expressed in the eye and many other tissues, such as brain, muscle, and liver as well. Transgenic zebrafish harboring an enhanced GFP reporter gene construct downstream of a 1.7-kb zlum 5'-flanking region displayed enhanced GFP expression in the cornea and sclera, as well as throughout the body. Down-regulation of zlum expression by antisense zlum morpholinos manifested ocular enlargement resembling axial myopia due to disruption of the collagen fibril arrangement in the sclera and resulted in scleral thinning. Administration of muscarinic receptor antagonists, e.g. atropine and pirenzepine, effectively subdued the ocular enlargement caused by morpholinos in in vivo zebrafish larvae assays. The observation suggests that zebrafish can be used as an in vivo model for screening compounds in treating myopia.

Gene‐environment interactions shape myopia development

Abstract Purpose Refractive development is highly heritable, yet also known to be regulated by visual experience during childhood. Recent genome‐wide association studies for refractive error have identified very few variants, which together explain only a small fraction of the population attributable risk. Gene‐environment interactions represent an attractive explanation for the paradoxical evidence supporting both genetic and environmental determination of refractive error, but to date their influence in complex disorders such as myopia is almost entirely unknown. Methods We carried out a selective breeding experiment in chicks monocularly deprived of sharp vision for 4 days, starting when they were 4 days old. Chicks in the extremes of the myopia susceptibility frequency distribution were retained for breeding. Heritability was estimated using variance components analysis with the SOLAR package. Results After 2 rounds of selection, chicks bred for low susceptibility developed less than half the treatment‐induced myopia of those bred for high susceptibility ("Low line" = ‐6.88 ± 3.35 D; "High line" = 15.27 ± 3.47 D; mean ± SD; N = 392; P ~10e‐80). Susceptibility to induced myopia was highly heritable (heritability = 0.53; N = 891; p ~10e‐122). Furthermore, the Low line developed only half the myopia of the High line in response to a second type of environmentally‐induced myopia, minus lens wear. The genetic variants that determined myopia susceptibility were found to be distinct from those controlling natural variations in eye size. Conclusion This work reveals that genetic variants determine susceptibility to myopia triggered by cues from the visual environment, implicating a potentially major role for gene‐environment interactions in human myopia development.

Peripheral refraction and the development of refractive error: a review

It has been suggested that emmetropic and low-hyperopic eyes in which the refractive error in the periphery of the visual field is relatively hyperopic with respect to the axial refraction may be at greater risk of developing myopia than eyes with similar refractions but relatively myopic peripheral refractive errors. The animal and human evidence to support this hypothesis is reviewed. The most persuasive studies are those in which emmetropization has been shown to occur in infant rhesus monkeys with ablated foveas but intact peripheral fields, and the demonstration that, in similar animals, lens-induced relative peripheral hyperopia produces central axial myopia. Evidence for emmetropization in animals with severed optic nerves suggests that emmetropization is primarily controlled at the retinal level but that the higher levels of the visual system play a significant role in refining the process: there appear to be no directly equivalent human studies. Since any contribution of the higher centres to the control of refractive development must depend upon the sensitivity to defocus, the results of human studies of the changes in depth-of-focus across the field and of the contribution of the retinal periphery to the accommodation response are discussed. Although peripheral resolution is relatively insensitive to focus, this is not the case for detection. Moreover accommodation occurs to peripheral stimuli out to a field angle of at least 10 deg, and the presence of a peripheral stimulus can influence the accommodation to a central target. Although the basic hypothesis that a relatively hyperopic peripheral refractive error can drive the development of human myopia remains unproven, the available data support the possibility of an interaction between the states of focus on axis and in the periphery.

Ocular blood flow measurements in healthy human myopic eyes

To evaluate the haemodynamic features of young healthy myopes and emmetropes, in order to ascertain the perfusion profile of human myopia and its relationship with axial length prior to reaching a degenerative state. The retrobulbar, microretinal and pulsatile ocular blood flow (POBF) of one eye of each of twenty-two high myopes (N = 22, mean spherical equivalent (MSE) ≤-5.00D), low myopes (N = 22, MSE-1.00 to-4.50D) and emmetropes (N = 22, MSE ± 0.50D) was analyzed using color Doppler Imaging, Heidelberg retinal flowmetry and ocular blood flow analyser (OBF) respectively. Intraocular pressure, axial length (AL), systemic blood pressure, and body mass index were measured. When compared to the emmetropes and low myopes, the AL was greater in high myopia (p < 0.0001). High myopes showed higher central retinal artery resistance index (CRA RI) (p = 0.004), higher peak systolic to end diastolic velocities ratio (CRA ratio) and lower end diastolic velocity (CRA EDv) compared to low myopes (p = 0.014, p = 0.037). Compared to emmetropes, high myopes showed lower OBFamplitude (OBFa) (p = 0.016). The POBF correlated significantly with the systolic and diastolic blood velocities of the CRA (p = 0.016, p = 0.036). MSE and AL correlated negatively with OBFa (p = 0.03, p = 0.003), OBF volume (p = 0.02, p < 0.001), POBF (p = 0.01, p < 0.001) and positively with CRA RI (p = 0.007, p = 0.05). High myopes exhibited significantly reduced pulse amplitude and CRA blood velocity, the first of which may be due to an OBF measurement artefact or real decreased ocular blood flow pulsatility. Axial length and refractive error correlated moderately with the ocular pulse and with the resistance index of the CRA, which in turn correlated amongst themselves. It is hypothesized that the compromised pulsatile and CRA haemodynamics observed in young healthy myopes is an early feature of the decrease in ocular blood flow reported in pathological myopia. Such vascular features would increase the susceptibility for vascular and age-related eye diseases.

Genetic Association of Insulin-like Growth Factor-1 Polymorphisms with High-Grade Myopia in an International Family Cohort

Evidence from human myopia genetic mapping studies (MYP3 locus), modulated animal models, and observations of glycemic control in humans suggests that insulin-like growth factor (IGF)-1 plays a role in the control of eye growth. This study was conducted to determine whether IGF-1 polymorphisms are associated with myopia in a large, international dataset of Caucasian high-grade myopia pedigrees. Two hundred sixty-five multiplex families with 1391 subjects participated in the study. IGF-1 genotyping was performed with 13 selected tag single nucleotide polymorphisms (SNPs) using allelic discrimination assays. A family-based pedigree disequilibrium test (PDT) was performed to test for association. Myopia status was defined using sphere (SPH) or spherical equivalent (SE), and analyses assessed the association of (1) high-grade myopia (<or=-5.00 D), and (2) any myopia (<or=-0.50 D) with IGF-1 markers. Results were declared significant at P<or=0.0038 after Bonferroni correction. Q values that take into account multiple testing were also obtained. In all, three SNPs-rs10860860, rs2946834, and rs6214-were present at P<0.05. SNP rs6214 showed positive association with both the high-grade- and any-myopia groups (P=2x10(-3) and P=2x10(-3), respectively) after correction for multiple testing. The study supports a genetic association between IGF-1 and high-grade myopia. These findings are in line with recent evidence in an experimental myopia model showing that IGF-1 promotes ocular growth and axial myopia. IGF-1 may be a myopia candidate gene for further investigation.

Homeomorphic Matlab Model of Myopia Development

A homeomorphic biomechanical model of the eye based on the Incremental Retinal-Defocus Theory (IRDT) was developed to simulate myopic and hyperopic growth under different optical defocus conditions. The IRDT states that the time-integrated reduction in retinal-image defocus magnitude decreases the rate of retinal neuromodulator release, which in turn decreases the rate of proteoglycan synthesis and reduces scleral structural integrity, thus resulting in axial elongation and myopia development. A homeomorphic biomechanical model of the eye was constructed to test the IRDT based only on optical defocus and its resultant contribution to mechanical forces acting on the components of the eye. The Matlab simulation results showed a more fl attened oblate shape for myopic defocus, and a more elongated prolate shape with hyperopic defocus. Thus, the homeomorphic biomechanical model of the eye was able to simulate the emmetropization mechanism using only the forces acting on the masses at the nodes. In addition, neurochemicals injected at local retinal regions modifi ed the spring constants to result in predicted changes in ocular deformation. The fi ndings have clinical implications with respect to basic theories of myopia development, as well as future therapeutic use of direct ocular drug delivery to control human myopia.

Mouse Experimental Myopia Has Features of Primate Myopia

Several recent studies have suggested that experimental myopia can be induced in mice. However, it is not clear what role the photopic visual input plays in this process and whether mouse myopia is similar to human myopia. The purpose of this study was to carry out an in vivo high-resolution analysis of changes in ocular components and refractive state of the eye upon induction of experimental myopia in mice. A high-resolution small animal MRI system and a high-resolution automated eccentric infrared photorefractor were used to analyze changes of the refractive state and ocular components in C57BL/6J mice associated with experimental myopia induced by diffusers and -25 D lenses under photopic conditions. The authors found that both diffusers and -25 D lenses induce myopia in C57BL/6J mice under photopic conditions (continuous light, 200 +/- 15 lux). The extent of myopic shift induced by -25 D lenses was greater than the shift induced by diffusers (-15.2 +/- 0.7 D, lenses; -12.0 +/- 1.4 D, diffusers). Myopia in mice is attributed to an increase in size of the postequatorial segment of the eye. Experimental myopia in mice can be induced only during the susceptible period in postnatal development, which ends around postnatal day 67. Both diffusers and spectacle lenses induce myopia in mice under photopic conditions, during the susceptible period in postnatal development. Myopia in mice is associated with elongation of the vitreous chamber of the eye, as in humans and nonhuman primates.

Monochromatic aberrations of the human eye and myopia

Background: The relationship between monochromatic aberrations of the human eye and myopia has been investigated extensively over the past decade or so but the results are inconclusive. Wide age range, narrow refractive error range and large individual variations are common confounding factors in previous studies. To address these shortcomings, we conducted a two‐part study. The first part set out to determine whether the monochromatic aberrations in myopic eyes are different from those in the non‐myopic eyes in adults. Subjects were drawn from a narrow age band to minimise the confounding effect of age. The second part of this study compared the monochromatic aberrations of the more myopic and less myopic eyes of anisometropes.Methods: Monochromatic aberrations were measured for 5-mm pupils using the Complete Ophthalmic Analysis System (COAS) Wavefront Analyzer in 116 subjects with refractive spherical equivalent between ‐10.38-D and +1.38-D and in 26 anisometropes. Measurements were done in a dark room with natural pupils. The refractive errors, corneal curvatures and axial lengths of the eyes were measured under natural accommodation.Results: Highly myopic eyes had significantly smaller root mean square (RMS) values of fourth order (p = 0.015) and spherical aberrations (p = 0.009) than non‐myopic eyes. The correlation coefficient was 0.2354 (p = 0.011) between fourth‐order aberrations and refractive spherical equivalents and 0.2817 (p = 0.002) between spherical aberration and refractive spherical equivalents. Less myopic eyes of the anisometropes showed significantly larger total higher‐order, third‐order and spherical aberrations than the more myopic eyes (p < 0.05, p < 0.05 and p < 0.01, respectively).Conclusions: Our study shows that spherical aberration is associated with refractive error. More myopic eyes tended to have smaller amounts of spherical aberration, however, the ‘cause or effect’ question remains. Longitudinal studies are needed to further investigate the relationship between monochromatic aberrations and refractive development.

Temporal Properties of Compensation for Positive and Negative Spectacle Lenses in Chicks

Chicks' eyes rapidly compensate for defocus imposed by spectacle lenses by changing their rate of elongation and their choroidal thickness. Compensation may involve internal emmetropization signals that rise and become saturated during episodes of lens wear and decline between episodes. The time constants of these signals were measured indirectly by measuring the magnitude of lens compensation in refractive error and ocular dimensions as a function of the duration of episodes and the intervals between the episodes. First, in a study of how quickly the signals rose, chicks were subjected to episodes of lens-wear of various durations (darkness otherwise), and the duration required to cause a half-maximum effect (rise-time) was estimated. Second, in a study of how quickly the signals declined, various dark intervals were imposed between episodes of lens-wear, and the interval required to reduce the maximum effect by half (fall-time) was estimated. The rise-times for the rate of ocular elongation and choroidal thickness were approximately 3 minutes for positive and negative lenses. The fall-times had a broad range of time courses: Positive lenses caused an enduring inhibition of ocular elongation with a fall-time of 24 hours. In contrast, negative lenses caused a transient stimulation of ocular elongation with a fall-time of 0.4 hour. The effects of episodes of defocus rise rapidly with episode duration to an asymptote and decline between episodes, with the time course depending strongly on the sign of defocus and the ocular component. The complex etiology of human myopia may reflect these temporal properties.

Pharmacological control of myopia ‐ current options and future possibilities

Abstract Purpose To review current pharmacological options for myopia control and explore future options. The underlying cause of both myopia and associated retinal complications is excessive ocular growth, which is a logical target for pharmacological intervention. Methods This presentation will review relevant research using animal models for myopia as well as clinical myopia research. Results The first attempts to control human myopia with drugs date back to the middle of the 19th century and involved topical atropine, an antimuscarinic drug. Possible reasons for why it remains the only drug in wide‐spread use for myopia control today, despite its significant adverse ocular side‐effects, will be considered along with general and drug‐specific clinical issues associated with long‐term use of topical ophthalmic formulations. Other plausible pharmacological treatment options will also be explored. Conclusion Progress in developing acceptable drug treatments for myopia control has been disappointing, especially given the near epidemic levels of myopia in some countries. However, the increased attention paid to the translation value of biomedical research may help to change this situation.

Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia.

Simultaneous Defocus Integration during Refractive Development

To determine the effects of simultaneously presented myopic and hyperopic defocus on the refractive development of chicks. A novel form of dual-power lens was designed. Normal chicks 7 to 8 days of age were fitted with a dual-power lens over one eye and a plano lens over the fellow (control) eye. Dual-power lenses of +20/-10, +10/-10, +5/-10, and plano/-10-D were tested, along with +10/-10-D lenses having differing ratios (50:50, 33:67, and 25:75) of surface area devoted to each power. Ocular refraction and axial ocular component dimensions were assessed after 6 days of lens wear, by retinoscopy and high-frequency ultrasound, respectively. In a separate experiment designed to test the effect of dual-power lens wear on the refractive development of myopic eyes, chicks were fitted with a dual-power +10/-10-D lens for 6 days, after myopia had been induced by 6 days of -10-D lens wear. For each of the dual-power lenses tested, the refractive end point of the treated eye was found to lie between the two optical powers of the lens (but with the response weighted in favor of the effect of myopic defocus). Refractive development appeared to be modulated by the sign, dioptric magnitude, and relative contribution (relative contrast) of the imposed optical defocuses through an integrative mechanism. Chicks with myopia induced by -10-D lens wear recovered when treated with a +10/-10-D dual-power lens. The chick retina can discern both the sign and the magnitude of optical defocus. Chick eyes were able to integrate blur cues from simultaneously presented images focused either side of the photoreceptors and to modulate their refractive development accordingly. This implies that the complex nature of defocus in the visual environment may play a critical role in the pathogenesis of myopia. The results suggest a rational method for arresting or reversing the development of myopia, which may be useful in the treatment of human myopia if the primate retina is also capable of responding to simultaneously presented opposing defocus cues.

Evaluation of inner retinal function in myopia using oscillatory potentials of the multifocal electroretinogram

Purpose Oscillatory potentials have been suggested to arise from the inner retina at the level of amacrine cells and inner plexiform layer and they are thought to provide a non-invasive assessment of inner retinal function. We sought to investigate the response dynamics of the inner retina of adult emmetropes and myopes by analysing the oscillatory potentials of the multifocal electroretinogram (mfERG) in these groups. Methods Eleven emmetropes and 18 myopes underwent mfERG testing using VERIS 5.1.5X. Myopes were further separated based on whether their myopia was stable ( n = 9) or progressing ( n = 9). Oscillatory potentials were recorded using a modified mfERG stimulation technique, the slow flash paradigm, and they were extracted using band-pass filtering from 100 to 300 Hz. The slow flash mfERG stimulus array consisted of 103-scaled hexagons and flickered according to a pseudorandom binary m-sequence (2 13–1). Amplitudes and implicit times of the first-order oscillatory potentials were analysed. Results There were significant differences in the implicit time of the oscillatory potentials of the emmetropes, stable myopes and progressing myopes ( F 2,25 = 3.663, p = 0.043). Progressing myopes had significantly shorter implicit times compared to emmetropes ( p = 0.026 by 1.0–4.7 ms) and stable myopes ( p = 0.043 by 0.8–1.3 ms), whereas implicit times of stable myopes and emmetropes were similar. There were no statistically significant differences in amplitude of the oscillatory potentials between the groups ( F 2,25 = 0.890, p = 0.426). Conclusions Significant differences in multifocal oscillatory potentials between stable and progressing myopes were found. This finding is further evidence of an inner retinal involvement in human myopia progression and may suggest an underlying alteration to dopaminergic or GABAergic retinal systems.

Form deprivation modulates retinal neurogenesis in primate experimental myopia

Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to this abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. After fusion of the lids in one eye of juvenile rhesus macaques and green monkeys, we combined cDNA subtractions, microarray profiling, and real-time PCR to compare gene expression in the retinas of the closed and open eyes. This molecular analysis showed up-regulation of a number of genes associated with cell division in the retina of the closed eye and differential expression of six genes localized to chromosomal loci linked to forms of human hereditary myopia. In addition, it substantiated a previous observation, based on immunocytochemistry, that synthesis of vasoactive intestinal polypeptide was increased upon lid fusion. Injection of 5-bromo-2'-deoxyuridine and immunocytochemistry showed that the primate retinal periphery harbors mitotically active neuroprogenitor cells that increase in number when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. Vasoactive intestinal polypeptide may be the molecule that stimulates retinal growth.