D.I. Flitcroft

A model of the contribution of oculomotor and optical factors to emmetropization and myopia

The purpose of this work was to investigate quantitatively the interactions between accommodation, vergence and a mechanism of emmetropization driven by optical blur within the retinal image with a view to developing a model that provides an explanation of both normal emmetropization and near-work associated myopia. The simulations of the change in the refractive state of the eye over time that derive from this model indicate that optical regulation of eye growth can result in emmetropization, i.e. a progressive reduction in refractive errors over time leading towards emmetropia. This occurs when viewing conditions involve a preponderance of distance work. With increasing near work, the model predicts that the refraction of the eyes will converge towards myopia. In keeping with the previously reported associations of myopia with esophoria, poor accommodation function and high AC/A ratios, these conditions increase the amount of myopia produced under intensive near viewing conditions but do not lead to myopia during mainly distance viewing. This model provides quantitative validation of the hypothesis that the epidemiological association between myopia and increased nearwork may be caused by a disturbance of normal emmetropization by steady state errors of accommodation. The same model can explain normal emmetropization, increasing myopia with increasing nearwork demands and the currently recognised oculomotor associations that have been reported to precede the development of myopia.

Intraocular lenses in children: changes in axial length, corneal curvature, and refraction

AIM To assess changes in axial length, corneal curvature, and refraction in paediatric pseudophakia. METHODS 35 eyes of 24 patients with congenital or developmental lens opacities underwent extracapsular cataract extraction and posterior chamber intraocular lens implantation. Serial measurements were made of axial length, corneal curvature, objective refraction, and visual acuity. RESULTS For patients with congenital cataracts (onset <1 year age) the mean age at surgery was 24 weeks. Over the mean follow up period of 2.7 years, the mean increase in axial length of 3.41 mm was not significantly different from the value of an expected mean growth of 3.44 mm (pairedt test, p=0.97) after correction for gestational age. In the developmental cataract group (onset >1 year of age) the mean age at surgery was 6.4 years with a mean follow up of 2.86 years. This group showed a mean growth in axial length of 0.36 mm that was not significantly different from an expected value of 0.47 mm (paired t test, p = 0.63). The mean preoperative keratometry was 47.78 D in the congenital group and 44.35 D in the developmental group. At final follow up the mean keratometry in the congenital group was 46.15 D and in the developmental group it was 43.63 D. In eyes followed for at least 2 years, there was an observed myopic shift by 24 months postoperatively of 3.26 D in the congenital cases (n=10) and 0.96 D in the developmental cases (n=18). CONCLUSION The pattern of axial elongation and corneal flattening was similar in the congenital and developmental groups to that observed in normal eyes. No significant retardation or acceleration of axial growth was found in the eyes implanted with IOLs compared with normal eyes. A myopic shift was seen particularly in eyes operated on at 4–8 weeks of age and it is recommended that these eyes are made 6 D hypermetropic initially with the residual refractive error being corrected with spectacles.

Retinal dysfunction and refractive errors: an electrophysiological study of children

Aims: To evaluate the relation between refractive error and electrophysiological retinal abnormalities in children referred for investigation of reduced vision. Methods: The study group comprised 123 consecutive patients referred over a 14 month period from the paediatric service of Moorfields Eye Hospital for electrophysiological investigation of reduced vision. Subjects were divided into five refractive categories according to their spectacle correction: high myopia (⩽−6D), low myopia (>−6D and ⩽−0.75D), emmetropia (>−0.75 and <1.5D), low hyperopia (⩾1.5 and <6D), and high hyperopia (⩾6D). Patients with a specific diagnosis at the time of electrophysiological testing were excluded. Only the first member of any one family was included if more than one sibling had been tested. All tests were performed to incorporate ISCEV standards, using gold foil corneal electrodes where possible. In younger patients skin electrodes and an abbreviated protocol were employed. Results: The mean age of patients was 7.1 years with an overall incidence of abnormal electrophysiological findings of 29.3%. The incidence of abnormality was higher in high ametropes (13/25, 52%) compared to the other groups (23/98, 23.5%). This difference was statistically significant (χ2 test, p = 0.005). There was also a significant association between high astigmatism (>1.5D) and ERG abnormalities (18/35 with high astigmatism v 20/88 without, χ2 test, p = 0.002). There was no significant variation in frequency of abnormalities between low myopes, emmetropes, and low hyperopes. The rate of abnormalities was very similar in both high myopes (8/15) and high hyperopes (5/10). Conclusions: High ametropia and astigmatism in children being investigated for poor vision are associated with a higher rate of retinal electrophysiological abnormalities. An increased rate of refractive errors in the presence of retinal pathology is consistent with the hypothesis that the retina is involved in the process of emmetropisation. Electrophysiological testing should be considered in cases of high ametropia in childhood to rule out associated retinal pathology.

Is myopia a failure of homeostasis

This review examines the hypothesis that human myopia is primarily a failure of homeostasis (i.e. regulated growth) and also considers the implications this has for research into refractive errors. There is ample evidence for homeostatic mechanisms in early life. During the first few years of life the eye grows toward emmetropia, a process called emmetropization. The key statistical features of this process are a shift of the mean population refraction toward emmetropia and a reduction in variability. Refractive errors result when either this process fails (primary homeostatic failure) or when an eye that becomes emmetropic fails to remain so during subsequent years (secondary homeostatic failure). A failure of homeostasis should increase variability as well as causing a possible shift in mean refraction. Increased variability is indeed seen in both animal models of myopia such as form deprivation and in human populations from the age of 5 or 6 onwards. Considering ametropia as a homeostatic failure also fits with the growing body of evidence that a wide range of factors and events can influence eye growth and refraction from gestation, through infancy, childhood and into adulthood. It is very important to recognize that the refraction of an eye is not a simple trait like eye colour but the consequence of the complex process of eye growth throughout life. To understand how an eye ends up with a specific refraction it is essential to understand all the factors that may promote the attainment and maintenance of emmetropia. Equally important are the factors that may either disrupt early emmetropization or lead to a loss of emmetropia during later development. Therefore, perhaps the most important single implication of a homeostatic view of myopia is that this condition is likely to have a very wide range of causes. This may allow us to identify subgroups of myopia for which specific environmental influences, genes or treatments can be found, effects that might be lost if all myopes are considered to be equivalent.

Emmetropisation and the aetiology of refractive errors

The distribution of human refractive errors displays features that are not commonly seen in other biological variables. Compared with the more typical Gaussian distribution, adult refraction within a population typically has a negative skew and increased kurtosis (ie is leptokurtotic). This distribution arises from two apparently conflicting tendencies, first, the existence of a mechanism to control eye growth during infancy so as to bring refraction towards emmetropia/low hyperopia (ie emmetropisation) and second, the tendency of many human populations to develop myopia during later childhood and into adulthood. The distribution of refraction therefore changes significantly with age. Analysis of the processes involved in shaping refractive development allows for the creation of a life course model of refractive development. Monte Carlo simulations based on such a model can recreate the variation of refractive distributions seen from birth to adulthood and the impact of increasing myopia prevalence on refractive error distributions in Asia.

The lens paradigm in experimental myopia: oculomotor, optical and neurophysiological considerations.

The lens‐rearing paradigm has developed great importance in the field of experimental myopia. Although an apparently simple paradigm, the results of any experiment can be influenced by a variety of factors including habitual viewing distance, ocular refraction, oculomotor performance and the spatial sensitivity of the retinal elements involved in retinal image assessment. Computer modelling has been used to evaluate the expected impact when lenses are placed in front of a primate eye as a function of the above parameters. Spatial band‐pass responses of the mechanisms responsible for emmetropisation are predicted to lead to a limited range of retinal defocus over which compensation to lenses could occur. Even assuming an equal ability to detect hyperopic and myopic defocus, it is predicted that primate eyes should be able to compensate for a much larger range of minus lenses than plus lenses. This derives from the ability of the accommodation system to keep retinal defocus within this operating range over a wider range of minus lenses than plus lenses. The range over which compensation can occur will depend on the spatial tuning of the elements responsible for detecting retinal defocus and capabilities of the accommodation system. The observed asymmetry in responses of the primate eye to rearing with plus and minus lenses and observed differences between primates and chickens in lens rearing studies may therefore be partly attributable to optical and neurophysiological considerations.

The acceptability and visual impact of 0.01% atropine in a Caucasian population.

Background Myopia is a condition of enormous public health concern, affecting up to 2.5 billion people worldwide. The most effective treatment to prevent myopia progression is atropine but at the cost of accommodative paresis and mydriasis, necessitating the use of bifocal glasses. Low-dose atropine (0.01%) has been found to be almost as effective with significantly reduced side effects. Since there are well-recognised differences in the effect of atropine between heavily pigmented Asian eyes and Caucasian eyes, this study aimed to determine the acceptability and tolerability of 0.01% atropine (by measuring visual performance and quality of life) as a treatment for myopia control in a Caucasian population exhibiting light irides. Methods 14 university students aged 18–27 were recruited to the study. Participants received one drop of 0.01% atropine daily into each eye over 5 days. A range of physiological, functional and quality of life measures were assessed at baseline, day 3 and day 5. Results The effect of atropine was statistically significant for pupil size (p=0.04) and responsiveness (p<0.01). While amplitude of accommodation reduced, the change was not statistically significant. Visual acuity (distance and near) and reading speed were not adversely affected. While there was a slight increase in symptoms such as glare, overall there was no quality of life impact associated with the use of low-dose atropine. Conclusions Overall, 0.01% of atropine was generally well tolerated bilaterally and no serious adverse effects were observed. Therefore this dose appears to provide a viable therapeutic option for myopia control among Caucasian eyes.

Ophthalmologists should consider the causes of myopia and not simply treat its consequences

Myopia has been undergoing a major re-evaluation in recent years both by ophthalmologists and basic scientists, though for different reasons. For ophthalmologists the rise of refractive surgery in the past decade has seen myopia changing from a condition requiring optical correction to one that can be managed surgically with the aid of the excimer laser and other techniques. For basic scientists interested in the control of eye growth, the past decade has been equally revolutionary with a huge increase in the understanding of mechanisms by which eye growth is regulated by the quality of the retinal image. This research offers insights into why myopia develops in humans and offers clinicians a novel perspective from which to approach the management of myopia. Rather than attempting to alter corneal curvature to “treat” myopia, it may be possible to prevent or “cure” myopia by directly manipulating the growth mechanisms of the eye. Epidemiological studies indicate that myopia represents a growing public health problem, particularly in the Far East. Singapore, for example, has seen an increase in the prevalence of myopia in young adults from 26% to 43% over a decade, reaching 65% in university graduates.1 This increase largely reflects the increasing levels of youth onset myopia and adult onset myopia. There is a wide variety of epidemiological evidence that suggests that environmental effects can influence the development of these forms of myopia. Within the Singaporean population, both the prevalence and degree of myopia correlate with the time spent in full time education.2 In populations with little genetic heterogeneity, such as Inuit populations, studies have revealed that within a generation, the incidence of myopia has risen dramatically in line with the onset …

Targeted mydriasis strategies for diabetic retinopathy screening clinics

PurposeTo examine factors necessitating pupil dilation to achieve gradable diabetic screening photographs using a digital non-mydriatic camera and to establish techniques to predict the need for dilation and to validate them.MethodsProspective clinic-based cross-sectional study with follow-up validation study. The participants’ involved consecutive patients attending the diabetic retinopathy screening clinic at a University Hospital. Best corrected visual acuity, age, sex, pupil size, mean spherical equivalent, cataract grade and the requirement for dilation to achieve gradable photographs in 90 patients were recorded. Data analysis using principal component analysis and multivariate analysis of variance derived a set of equations to predict the requirement for dilation. The predictive powers of these equations were validated in an independent group of 51 patients.ResultsSmaller pupil size, denser nuclear colour, older age, poorer best-corrected visual acuity, cortical lens opacity and posterior subcapsular lens opacity were associated with the need for dilation (P<0.001 in all). Single variables used in isolation had a poorer predictive value than combining variables. Dilating patients with either a pupil size >3.75 mm or age >59 years correctly allocates 83 and 78% of patients, respectively to dilation or not. Combining pupil size with age produces a decision table that improves the predictive value to 84%. In the validation study this table had a predictive value of 80%.ConclusionWe have produced and validated criteria based on a range of clinical variables for application in a clinical setting that allows for the development of targeted mydriasis.