CONGENITAL AND DEVELOPMENTAL

WAYNE G. WHITMORE New York

SUMMARY growth of the refractive tissues toward emmetropia.

Both hereditary and environmental factors are impor­ Largely on the basis of experimental studies reviewed tant in the interactive growth of the ocular tissues respon­ elsewhere,2,3 it is felt that emmetropisation is an active sible for determining the refractive state of the eye. process and not just a passive independent growth of the Myopia has a low prevalence in otherwise healthy chil­ ocular tissues. Environmental factors play a modifying dren and is seen with an increased prevalence early in life role on the refractive state of the eye, with hereditary fac­ in many systemic and ocular diseases. Predicting how tors being the primary determinant of the ocular refractive will change in any individual child after state. birth or at any stage of ocular development is not possible Table I shows the range of average measurements of the at present, although, trends can be seen in longitudinal refractive components at birth, three years, and adulthood, studies. In the disease states associated with an increased as determined by the work of several authors in different prevalence of Plyopia, information regarding the time of studies reviewed by Curtin,' and in a more recent study.4 onset of myopia and the specific values for the refractive Variations in these measurements among the different components, is lacking, so that underlying mechanisms of investigators can be accounted for by the different myopia development and whether the myopia is congeni­ methods of calculation and measurement, population bias, tal or developmental, are not known. In adults, three dif­ and different definitions for age groups. Regardless of the ferent types of myopia can be characterised on the basis variation in these measurements, it is obvious that a large of clinical characteristics which have prognostic signifi­ amount of axial growth and corneal flattening takes place cance for ocular disease. The mechanisms of ocular over the first few years of life, with the eye reaching vir­ growth that lead to these forms of myopia are not clear. tually adult proportions after just a few years. The decreas­ At present, treatments to prevent or slow myopic pro­ ing power along with the decreasing corneal power gression have been marginally beneficial and of question­ largely offsets the myopigenic axial growth of the eye able value. such that the adult refraction becomes emmetropic rather NORMAL OCULAR GROWTH than myopic.

The development of ocular refraction is the result of a CLASSIFICATION OF MYOPIA complex interaction between the growth of various ocular tissues. Corneal power, lens power, axial length, and From both a practical and theoretic standpoint, it is impor­ anterior chamber depth (along with the respective indicies tant to distinguish between the different types of myopia of refraction of the different media) combine to determine seen in humans. In physiologic myopia (also called the refractive state of the eye. Statistical analysis has 'simple' or 'refractive' myopia), there is a mismatch of the shown that significant correlations exist between the refractive components, all of whose values fall within refractive components in emmetropic eyes of adults. their normal statistical ranges. Axial (or 'intermediate') Through infancy and childhood, these components myopia results from excessive enlargement of the pos- undergo changes which result in the average refractive Table I. Average Ocular Measurements for the Refractive state changing from mild hyperopia to emmetropia. Since Components in Random Samples of Healthy Patients an overwhelming preponderance of emmetropia is seen in Newborn Three-year-old Adult the adult population, there appears to be a developmental process (so-called 'emmetropisation') which results in Refraction 0.4-2.6 D 0.6-3.0 D -0.5-p lano Corneal power 51-55 D 43 -44D 43 -43,5 D From: New York Hospital -Cornell University Medical Center, AC depth 2.4-2.9 mm 3.3mm 3.5mm New York, New York Axial length* 16.7- 17.5mm 22mm 22.8 -23.5mm G. Correspondence to: Wayne Whitmore, M.D., 1001Park Avenue, Lens power 25-34D 22 D 19-20 D New York, New York 10028.

Eye (1992) 6, 361-365 362 WAYNE G. WHITMORE

terior segment and can usually be distinguished from Table II. Congenital and De velopmental Myopia refractive myopia by the clinical findingsof temporal cres­ L Associated with systemic disease (exclusive of other ) cents on the optic discs, straightening of the retinal albinism vessels, and fundus tessellation (retinal thinning). Axial cerebral palsy myopia is associated with an increased risk of peripheral Cornelia De Lang syndrome retinal degenerations, retinal detachments, and glau­ Ehler's-Danlos syndrome coma. 1 Pathologic myopia is a special form of axial myo­ Fabray's disease hereditary arthro-ophthalmopathies pia, defined clinically by the presence of a posterior homocystinuria staphyloma. In addition to being associated with the afore­ Noonan syndrome mentioned complications of axial myopia, it is associated Pierre-Robin syndrome with the development of chorioretinal degeneration within Riley-Day syndrome (familial dysautomonia) the posterior staphyloma which usually leads to profound trisomy 21, 22, 16, 17, and 13 (?) vision loss with advancing age. The distinction between 2, Associated with ocular disease these different forms of myopia may not be clear early in a) without systemic disease (rod ,blue cone life, but with advancing age it usually becomes evident. monochromacy) An attempt to categorise myopia by the aforementioned choroideraemia types is useful not only in prognosis, but also in helping to coloboma understand the mechanisms responsible for the develop­ corneal scarring or opacification ment of myopia which appear to be different in these dif­ congenital stationary night blindness ferent forms of myopia. familial exudative vitreoretinopathy fundus flavimaculatus MYOPIA PREVALENCE AND gyrate atrophy DEVELOPMENT 1ansen's vitreoretinal degeneration The prevalence of myopia in the normal term newborn is microcornea probably between 4% and 6%, although a literature review microphthalmos (nanophthalmos) shows extremes of 1 % and 25%1 Only 1 % to 2% of this microphakia myelinated nerve fibres myopia is high. Low myopia appears to resolve or decrease over the first few months of life. The incidence of hypoplasia myopia remains fairly stable over the first few years of life pigmentosa but shows an increase with advancing age through child­ of prematurity hood. This increase is seen at about the time children are vitreous haemorrhage Wagner's vitreoretinal degeneration beginning school and this has implicated near work (and b) associated with systemic disease ) as a cause for the development of myo­ albinism pia. Studies of the prevalence of myopia in adults show a cataract -Alport syndrome, Fabray's disease, wide variation (from 8% in Sweden to 52% in China) congenital rubella, Marfan syndrome, homocystinuria, depending on the population and the adult age groups artho-ophthalmopathies examined. congenital external ophthalmoplegia -Fabray's disease, hereditary In the premature infant, studies of refractions show eyes arthro-ophthalmopathies to be more myopic or less hyperopic than the normal term ectopia lentis -dwarfism, Ehler's-Danlos infant.4,s The prevalence of myopia appears to be greater syndrome homocystinuria, Marchesani syndrome, Marfan syndrome, with decreasing birthweight.4,6 The myopia of prematurity arthro-ophthalmopathies (excluding infants with retinopathy of prematurity) glaucoma -homocystinuria.congenital rubella, microphthalmia, arthro-ophthalmopathies appears to be low in degree, is not associated with fundus lenticonus -Alport syndrome changes typical of myopia, and usually regresses over the keratoconus -homocystinuria, Marfan syndrome, firstyear of life. It is uncertain how the refractive compon­ Marchesani syndrome, Laurence-Moon-Bardet- Biedl syndrome, trisomy 21. ents change to account for this shift in refraction, Noonan syndrome In utero, ocular growth proceeds according to poorly microphakia -Marchesani syndrome, Marfan syndrome understood genetic factors. Environmental disturbances at microphthalmia -arthro-ophthalmopathies this time (i.e, maternal illness) may upset the normal retinopathy -congenital rubella, relationships between the refractive components resulting arthro-ophthalmopathies, Ehler's-Danlos syndrome, ROP (?) in the presence of myopia at birth or in conditions which spherophakia -Marfan syndrome lead to the development of myopia in early childhood. vitreoretinal degenerations -Stickler syndrome, spondyloepiphyseal dysplasia Congenital and developmental myopia can be seen in association with systemic disease, with ocular disease 3, Isolated myopia (no other known pre-existingeye or systemic associated with systemic disease, with ocular disease disease) a)refractive myopia ('simple', 'physiologic' or 'correlation' alone, or as anisolated finding (Table II). The type of myo­ myopia) pia (refractive or axial) or whether it is congenital or b)axial myopia (,intermediate' myopia) c) pathologic myopia ('degenerative' myopia) developmental, is not known in most of these diseases. CONGENITAL AND DEVELOPMENTAL MYOPIA 363

To detennine the aetiology of myopia, it is logical to and within the eye from ocular accommodation and con­ look for common characteristics among the diseases in vergence) have been the focus of attention for a good part which it has an increased prevalence. Unfortunately, of this century. Coleman has postulated an aqueous-vit­ because of the variable frequency with which myopia reous pressure gradient (pressure greater in the vitreous) presents in the different diseases and our almost total lack during accommodation,21 which presumably could result of information with regard to the actual mesurements of in increased stress on the with consequent stretch­ the refractive components of these eyes at any stage in ing and elongation of the . Supporting the theory that development, it is difficult to fonn any conclusions at the the mechanical influence of accommodation results in present time. There are, however, several conditions myopia is the fact that atropine has been shown to slow or which appear to simulate the deprivation myopia seen in arrest the progression of low grade myopia in adoles­ nonhuman primates 7 and can be classified as develop­ cents.22,23 The effect is not marked and may diminish over mental fonns of axial myopia. Uniocular visual depri­ time after atropine has been stopped. Cyclopentolate and vation in neonates with ,8,9 ptosis, 10 appear to be ineffective.1 corneal scarring,II,12 myelinated nerve fibres in the ret­ Without any cycloplegic medications, a recent random­ ina,13,14 vitreous haemorrhage,15 and optic nerve hypo­ ised study in myopic schoolchildren showed that the pro­ plasia,16,17 all show a trend toward axial elongation and gression of myopia could not be stopped by using bifocals myopia in the involved eye. Myopia as a result of astig­ or removing myopic spectacles for reading or near work.24 matism induced by hemangiomas of the may also On the contrary, myopic progression appeared to be less in have a similar mechanism.18 Cataract, ptosis, vitreous the reference group who wore their full myopic correction haemorrhage, and corneal scarring with onset in adult­ at all times (although this finding was not statistically sig­ hood have not been reported to cause myopia. As in nificant). A faster progression of myopia was seen in all experimental studies, it appears that the earlier the onset of three treatment groups in those children who spent a the visual deprivation in ocular development, the greater greater amount of time reading or at near work. This latter the axial elongation. I 1 It is uncertain how the mechanisms finding, as well as the failure of bifocal correction to slow involved in this form of developmental myopia relate to the progression of myopia, was also reconfinned by bilateral myopia where there is no obvious opacification Jensen.19 of the ocular media. The importance of scleral stress and intraocular pres­ sure in the development of ocular refraction has been THEORIES AND TREATMENTS reviewed by Pruett.25 The increased prevalence of myopia Although it has been shown that there is a higher risk of seen in juvenile glaucoma as well as the increased preva­ myopic progression in children with myopic fundus lence of glaucoma associated with pathologic myopia, changes, with intraocular pressures above 16 mm Hg, and emphasises this relationship. In a recent controlled study with myopia greater than or equal to 3.00 diopters,19 for using schoolchildren aged 9-12 years, timolol maleate the most part it has been assumed, from the increasing was given over a two-year period.19 Despite a significantly prevalence of myopia seen with age in children, that myo­ lower intraocular pressure in the treated group of between pia tends to progress. This may not, however, be the case 2 and 3 mm Hg, no significant benefit was seen with for any individual child. Unfortunately, this means that regard to slowing the progression of myopia. The treat­ some children will be treated for myopic progression ment period and the degree of intraocular pressure low­ unnecessarily. This has begged caution with regard to ering were relatively small, but the absence of any trend treatment since the morbidity of myopia is relatively low. whatsoever, is discouraging. Nonsurgical methods of treating the progression of Van Alphen has postulated that the and myopia have lately focused in several areas; on reducing have a baseline tonus, independent of accommo­ ocular accommodation by medications or by the use of dation, which mitigates the effect of intraocular pressure bifocal spectacles; on reducing scleral stress by lowering on the stretching of sclera nonnally seen with ocular intraocular pressure; and on flattening the through development.26 According to his theory, the autonomic the use of rigid contact lenses. nervous system plays a key role in adjusting the baseline The firstof these forms of treatment is a consequence of tonus to achieve emmetropia and he suggests that stress the observation that a visual experience requiring focusing (i.e., sympathetic nervous stimulation from perfonnance at near over long periods of time, is associated with a anxiety in schoolchildren) leads to a decrease in this tonus, higher prevalence of myopia. The mechanism by which allowing the full force of intraocular pressure to be trans­ prolonged accommodation, convergence, and/or near mitted to the scleral wall with the consequent development visual input over long periods of time might cause the of ocular enlargement and myopia. That anxiolytic medi­ increased prevalence of myopia seen in humans with a cations might prevent myopia development or slow myo­ visual experience of this nature, is still debated. Experi­ pic progression is intriguing but there has been no research mental deprivation myopia in animals suggests that retinal along these lines to date. image focus (through biochemical or neurochemical Studies dealing with the effect of rigid contact lenses on mechanisms) may be a factor in the development of myo­ the prevention of myopic progression can be summarised pia,20 but mechanical factors (i.e. the physical forces on by saying that most of the effect seen on slowing the pro- 364 WAYNE G. WHITMORE gression of myopia is due to corneal ftattening.27,28 Any the refractive state of the eye are unknown at present. effect on reducing axial growth, if it exists, might be Recent experimental studies, however, suggest that dopa­ explained by the differences in the clarity of focus in the mine metabolism may be important in myopia develop­ peripheral between these two different methods of ment. 36,37 Retinal levels of dopamine have been shown to optical correction. Peripheral retinal defocus induced by decrease significantly in form-deprivation myopia in both spectacle correction, may result in ocular expansion and chickens and monkeys when compared to control eyes. myopia development through mechanisms similar to When apomorphine, a dopamine agonist, is instilled in those seen in deprivation myopia in animals.20 form-deprived eyes of both the chick and the monkey, it Scleral reinforcement is a surgical treatment reserved prevents the development of axial myopia. for pathologic myopia and should probably only be used Continued experimental research along these lines, will in patients before the onset of visual deterioration from certainly improve our understanding of myopia develop­ myopic macular degenerative changes. The object of the ment and, hopefully, lead to ways in which we can control treatment is to prevent further elongation of the globe with ocular growth and modulate ocular refraction. It is in its attendent chorioretinal thinning and atrophy. Unfor­ infancy and during childhood, that we will have the best tunately, although there are many reports attesting to its chance at modulating the growth of the eye and in preven­ efficacy, the only long-term controlled study (using fellow ting the development and progression of myopia. eyes for the control) with axial length measurements, failed to demonstrate the ability of this procedure to pre­ REFERENCES & vent further axial elongation of the globe?9 Peri scleral col­ 1. Curtin BJ: 'The Myopias', Harper Row, Publishers, Phila­ delphia 1985 pp. 17-27,72-97,169-175. lagen grafts, although they maintain their postion over 2. Whitmore WG: The etiology of myopia. Curr OnOphthal­ long periods of time and may appear to have some rein­ mol 1991, 2: 72-7. forcing effect, do not appear to benefit the recipients.3o It 3. 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