Rural-urban differences in myopia prevalence among myopes presenting to Bhutanese retinal clinical services: a 3-year national study.

PURPOSE: To determine the prevalence and demographic characteristics of myopia among patients presenting to the national vitreo-retinal (VR) services in Bhutan. METHODS: The records of the VR clinic at the apex national referral centre, providing the only VR services in the country, were reviewed to identify all new myopia patients over three years. Thus, we surveyed all referrals nationally. The patients were categorised into urban and rural females and males. We assessed myopia prevalence in each group by occupational and educational categories. We examined univariate prevalence data and a multivariate logistic regression (MLR) identified independent factors. RESULTS: Of 2913 cases 1544 (53.0%) were males. Females presented earlier (mean ±SD): overall 45.7 ± 21.9 cf. 48.6 ± 21.6 years, p = 0.003, and among myopes 23.9 ± 13.5 cf. 27.6 ± 18.6 years, p = 0.032. Myopia constituted 92.1% of refractive error, an overall prevalence of 12.3%. Myopia was more common among females (p = 0.01) and urbanites (p = 0.02). Myopia prevalence was highest among urban females (20.9%), followed by urban males (11.9%), rural females (6.8%), and rural males (5.2%). Logistic regression revealed that the odds of having myopia were increased by being a student (4.96 ×) or professional (1.96 ×), and decreased by rural living (1.75 ×), all p ≤ 0.038. CONCLUSIONS: This is the first study on myopia in Bhutan. As observed throughout East and Southeast Asia, the prevalence of myopia was higher in females and urbanites and positively associated with formal education. Given known risk factors, these prevalences may be driven by educational pressures and reduced time spent outdoors.

Time outdoors and the prevention of myopia.

Recent epidemiological evidence suggests that children who spend more time outdoors are less likely to be, or to become myopic, irrespective of how much near work they do, or whether their parents are myopic. It is currently uncertain if time outdoors also blocks progression of myopia. It has been suggested that the mechanism of the protective effect of time outdoors involves light-stimulated release of dopamine from the retina, since increased dopamine release appears to inhibit increased axial elongation, which is the structural basis of myopia. This hypothesis has been supported by animal experiments which have replicated the protective effects of bright light against the development of myopia under laboratory conditions, and have shown that the effect is, at least in part, mediated by dopamine, since the D2-dopamine antagonist spiperone reduces the protective effect. There are some inconsistencies in the evidence, most notably the limited inhibition by bright light under laboratory conditions of lens-induced myopia in monkeys, but other proposed mechanisms possibly associated with time outdoors such as relaxed accommodation, more uniform dioptric space, increased pupil constriction, exposure to UV light, changes in the spectral composition of visible light, or increased physical activity have little epidemiological or experimental support. Irrespective of the mechanisms involved, clinical trials are now underway to reduce the development of myopia in children by increasing the amount of time they spend outdoors. These trials would benefit from more precise definition of thresholds for protection in terms of intensity and duration of light exposures. These can be investigated in animal experiments in appropriate models, and can also be determined in epidemiological studies, although more precise measurement of exposures than those currently provided by questionnaires is desirable.

Form deprivation and lens-induced myopia: are they different?

In the following point-counterpoint article, internationally-acclaimed myopia researchers were challenged to defend the two opposing sides of the topic defined by the title; their contributions, which appear in the order Point followed by Counterpoint, were peer-reviewed by both the editorial team and an external reviewer. Independently of the invited authors, the named member of the editorial team provided an Introduction and Summary, both of which were reviewed by the other members of the editorial team. By their nature, views expressed in each section of the Point-Counterpoint article are those of the author concerned and may not reflect the views of all of the authors.

Changes in retinal alphaB-crystallin (cryab) RNA transcript levels during periods of altered ocular growth in chickens.

Changes in retinal crystallin gene expression have been implicated in the development of myopia in animal models. We therefore investigated the expression of alphaB-crystallin (cryab) in the chicken retina during periods of increased ocular growth induced by form-deprivation and negative lens-wear, and during periods of decreased ocular growth induced by diffuser removal from previously form-deprived eyes, and plus lens-wear. Cryab RNA transcript levels in the chicken retina were measured using semi-quantitative real-time RT-PCR, at times between 1 h and 10 days after the fitting of diffusers or negative lenses, and at times between 1 h and 3 days following the removal of diffusers from previously form-deprived eyes, or the addition of plus lenses. Changes in expression for each condition at each time-point are analysed relative to expression in retinas from age-matched untreated control birds. No change in relative expression of cryab RNA transcript was detected 1 h after fitting diffusers to induce form-deprivation myopia. A transient increase in cryab RNA transcript expression was detected around 1 day later (p = 0.02), but expression returned to control levels after three days. After 7 (p = 0.005) and 10 (p = 0.001) days, retinal cryab RNA transcript expression progressively increased relative to controls. After removal of the diffusers, to initiate recovery, cryab RNA transcript expression remained elevated, with only a slight return to control levels. During the development of lens-induced myopia, no changes in cryab RNA transcript expression relative to controls were seen on day 1, but increases were seen at 10 days (p = 0.004). No significant changes in retinal cryab RNA transcript expression were seen in response to plus lenses compared to either contralateral control values (MANOVA; F = 0.60, p = 0.48) or age-matched untreated values (MANOVA; F = 4.10, p = 0.08). Changes in retinal cryab RNA transcript expression were not systematically related to changes in the rate of eye growth. The role of the transient increase in cryab expression observed after 1 day of form-deprivation, which was not seen after fitting negative lenses, is unclear. The later increases in relative cryab expression seen during the development of form-deprivation and lens-induced myopia occur too late to have a major role in the differential regulation of eye growth between experimental and control eyes. Given that cryab is a member of the small heat shock protein family, the later increases may reflect the emergence of cell damage related to high myopic pathology in the experimentally enlarged eyes and retina.

Changes in the expression of Pax6 RNA transcripts in the retina during periods of altered ocular growth in chickens.

Genome-wide mapping studies have suggested a possible role for Pax6 in the development of myopia. We therefore investigated the expression of Pax6 RNA transcripts in the chicken retina during periods of increased ocular growth, induced by form-deprivation and negative lens-wear, and during periods of decreased ocular growth, induced by diffuser removal from previously form-deprived eyes, and plus lens-wear. Levels of Pax6 RNA transcripts in the chicken retina were measured using semi-quantitative real-time RT-PCR, at times between 1 h and 10 days after the fitting of diffusers or negative lenses, and at times between 1h and 3 days following the removal of diffusers from previously form-deprived eyes, or the addition of plus lenses. Pax6 expression was unaffected during the initial 3 days of the response to form-deprivation or negative lens-wear, when rapid rates of growth are well-established. Alterations in the expression of Pax6 RNA transcripts were only observed after 7-10 days of form-deprivation (7 days, -15.7 +/- 5.3%; 10 days, -32.0 +/- 10.3%), with a similar response not seen during negative lens-wear, when eye growth also increases, suggesting that these alterations are specific to form-deprivation, rather to changes in the rate of eye growth. The late changes in Pax6 expression observed during form-deprivation were rapidly reversed after diffuser removal, with the levels of Pax6 RNA transcripts returning to those seen in control birds by 3 days (1 h, -27.8 +/- 4.7%; 1 day, -16.9 +/- 4.8%; 3 days + 1.0 +/- 8.6%). Analogous changes were not seen in response to positive lenses in which eye growth is also slowed. Overall, the findings of this study do not support a role for Pax6 in the modulation of ocular growth during visual manipulation.

The epidemics of myopia: Aetiology and prevention.

There is an epidemic of myopia in East and Southeast Asia, with the prevalence of myopia in young adults around 80-90%, and an accompanying high prevalence of high myopia in young adults (10-20%). This may foreshadow an increase in low vision and blindness due to pathological myopia. These two epidemics are linked, since the increasingly early onset of myopia, combined with high progression rates, naturally generates an epidemic of high myopia, with high prevalences of "acquired" high myopia appearing around the age of 11-13. The major risk factors identified are intensive education, and limited time outdoors. The localization of the epidemic appears to be due to the high educational pressures and limited time outdoors in the region, rather than to genetically elevated sensitivity to these factors. Causality has been demonstrated in the case of time outdoors through randomized clinical trials in which increased time outdoors in schools has prevented the onset of myopia. In the case of educational pressures, evidence of causality comes from the high prevalence of myopia and high myopia in Jewish boys attending Orthodox schools in Israel compared to their sisters attending religious schools, and boys and girls attending secular schools. Combining increased time outdoors in schools, to slow the onset of myopia, with clinical methods for slowing myopic progression, should lead to the control of this epidemic, which would otherwise pose a major health challenge. Reforms to the organization of school systems to reduce intense early competition for accelerated learning pathways may also be important.

Egr-1 mRNA expression is a marker for the direction of mammalian ocular growth.

PURPOSE: The immediate early gene Egr-1 is thought to form part of the pathway that mediates abnormal ocular growth. This study investigated whether the mRNA expression levels of Egr-1 in a mammalian retina are modulated differentially, depending on the direction of ocular growth. METHODS: To induce accelerated growth and myopia, guinea pigs wore a -5 diopter (D) lens over one eye from 4 to 11 days of age. To induce inhibited growth, the lens was removed after 7 days of -5 D lens wear, and the eye allowed to recover from myopia for 3 days. Ocular parameters and Egr-1 mRNA levels were subsequently assessed, and compared to untreated fellow eyes and eyes from untreated littermates. Possible circadian changes in Egr-1 mRNA levels were also determined in 18 additional animals by taking measures every 4 hours during a 24-hour cycle. RESULTS: Ocular compensation to a -5 D lens occurred after 7 days (Δ -4.8 D, Δ +147 µm growth, N = 20). In 5 highly myopic eyes (Δ -7.4 D), Egr-1 mRNA levels in the retina were significantly downregulated relative to contralateral control (51%) and age-matched untreated (47%) eyes. Three days after the -5 D lens was removed, eyes had recovered from the myopia (Δ -0.5 D, relative change of +2.9 D, N = 4) and Egr-1 mRNA levels were significantly elevated relative to contralateral (212%) and untreated (234%) eyes, respectively. Normal Egr-1 mRNA expression was higher in the middle of the day than in the middle of the night. Immunolabeling showed strong Egr-1 reactivity in cell bodies in the inner nuclear and ganglion cell layers. CONCLUSIONS: Egr-1 mRNA levels in a mammalian retina show a bi-directional persistent response to opposing ocular growth stimuli. This suggests retinal Egr-1 might act as a signal for the direction of ocular growth in different species.

The effect of bright light on lens compensation in chicks.

PURPOSE: It has been shown that sunlight or bright indoor light can inhibit the development of deprivation myopia in chicks. It remains unclear whether light merely acts on deprivation myopia or, more generally, modulates the rate of emmetropization and its set point. This study was conducted to test how bright light interacts with compensation for imposed optical defocus. Furthermore, a dopamine antagonist was applied to test whether the protective effect of light is mediated by dopamine. METHODS: Experiment A: Chicks monocularly wore either -7 or +7 D lenses for a period of 5 days, either under normal laboratory illuminance (500 lux, n = 12 and 16, respectively) or under high ambient illuminance (15,000 lux, n = 12 and 16). Experiment B: Chicks wore diffusers for a period of 4 days, either under normal laboratory illuminance (500 lux, n = 9) or high ambient illuminance (15,000 lux), with the bright-light group intravitreally injected daily with either the dopamine D(2) antagonist spiperone (500 µM, n = 9) or a vehicle solution (0.1% ascorbic acid, n = 9), with an untreated group serving as the control (n = 6). Axial length and refraction were measured at the commencement and cessation of all treatments. RESULTS: Exposure to high illuminances (15,000 lux) for 5 hours per day significantly slowed compensation for negative lenses, compared with that seen under 500 lux, although full compensation was still achieved. Compensation for positive lenses was accelerated by exposure to high illuminances but, again, the end point refraction was unchanged, compared with that of the 500-lux group. High illuminance also reduced deprivation myopia by roughly 60%, compared with that seen under 500 lux. This protective effect was abolished, however, by the daily injection of spiperone, but was unaffected by the injection of a vehicle solution. CONCLUSIONS: High illuminance levels reduce the rate of compensation for negative lenses and enhance the rate for positive lenses, but do not change the set point of emmetropization (target refraction). The retardation of myopia development by light is partially mediated by dopamine, as the injection of a dopamine antagonist abolishes the protective effect of light, at least in the case of deprivation myopia.