[Prevention of myopia]. / Prävention der Myopie.

To avoid complications of high myopia the best solution would be to prevent myopia development from the very beginning. Many studies have suggested that the frequently quoted myopia boom is related to changes in visual experiences during more demanding education and not due to changes in genetic factors. To avoid myopia development it would therefore be best to carry out a better control of visual experience of children. In this article new approaches are described to record and improve visual habits in children, e.g. new sensors attached to the spectacle frames to document brightness, reading distance and reading duration, changes in text contrast polarity during reading, potential role of smartphones and some not yet fully explored orally applied substances to inhibit myopia.

[Comparative analysis of light sensitivity, depth and motion perception in animals and humans]. / Vergleichende Betrachtung von Lichtempfindlichkeit, Tiefenwahrnehmung und Bewegungswahrnehmung bei Tier und Mensch.

BACKGROUND: This study examined how humans perform regarding light sensitivity, depth perception and motion vision in comparison to various animals. OBJECTIVE: The parameters that limit the performance of the visual system for these different functions were examined. METHODS: This study was based on literature studies (search in PubMed) and own results. RESULTS: Light sensitivity is limited by the brightness of the retinal image, which in turn is determined by the f­number of the eye. Furthermore, it is limited by photon noise, thermal decay of rhodopsin, noise in the phototransduction cascade and neuronal processing. In invertebrates, impressive optical tricks have been developed to increase the number of photons reaching the photoreceptors. Furthermore, the spontaneous decay of the photopigment is lower in invertebrates at the cost of higher energy consumption. For depth perception at close range, stereopsis is the most precise but is available only to a few vertebrates. In contrast, motion parallax is used by many species including vertebrates as well as invertebrates. In a few cases accommodation is used for depth measurements or chromatic aberration. In motion vision the temporal resolution of the eye is most important. The ficker fusion frequency correlates in vertebrates with metabolic turnover and body temperature but also has very high values in insects. Apart from that the flicker fusion frequency generally declines with increasing body weight. CONCLUSION: Compared to animals the performance of the visual system in humans is among the best regarding light sensitivity, is the best regarding depth resolution and in the middle range regarding motion resolution.

[Current recommendations for deceleration of myopia progression]. / Gegenwärtiger Stand der Empfehlungen zur Minderung von Myopieprogression.

BACKGROUND: Epidemiologic data demonstrate a rise in myopia prevalence. Therefore interventions to reduce the risk of myopia and its progression are needed and increasingly often asked for. METHODS: Systematic literature search via PubMed in MEDLINE. RESULTS: Myopia progression can be reduced by the following means which are listed according to their efficacy: (1) Atropine eye drops low dosed to avoid clinically relevant side effects, (2) optical means aiming at the correction of peripheral hyperopic defocus, e. g., multifocal contact lenses, and (3) increased daylight exposure. CONCLUSION: Daylight exposure reduces the risk of incident myopia. Children should be advised to spend sufficient time outdoors, especially before and in primary school. Myopia progression can be effectively attenuated by low-dose topical atropine and multifocal contact lenses.

[Biological mechanisms of myopia]. / Biologische Mechanismen der Myopie.

Recent studies have confirmed that the prevalence of myopia has increased in most countries, that the increase must be due to environmental factors and that myopia is closely linked to the level of education. Extensive close-up work with short viewing distances, little outdoor activity and continuous exposure to low illumination are currently considered the major factors. It remains unknown how close-up work can stimulate eye growth. Animal models provide the possibility to manipulate visual experiences and to observe subsequent changes in eye growth. They have uncovered a number of unexpected aspects which have led to studies in children. When applied in low doses atropine (0.01 %) is effective against progression of myopia and shows no rebound effect after termination of the treatment, in contrast to treatment with previously used higher doses. While education cannot be limited in our society, there are now an increasing number of options to slow myopia progression so that high myopia is less frequently reached.

[Clinical risk factors for progressive myopia]. / Klinische Risikofaktoren der Myopieprogression.

The average worldwide frequency of myopia is approximately 30 % and is traditionally subdivided into school myopia and pathological myopia. A further distinction is made between progressive myopia and stationary myopia. There is a high correlation between the frequency of myopia and urbanization and training. Risk factors for development of myopia are close-up work, lack of outdoor activity, biometrical variables of the eye and genetic risk factors. Development of myopia can be positively influenced by peripheral focusing, increased exposure to light and in the future possibly pharmacologically.

[Myopia update 2011]. / Myopie-Update 2011.

This review summarises some recent aspects of myopia research. The following conclusions have been drawn. As long as myopia progression is visually controlled, at least three different interventions are possible: (i) spectacles/contact lenses which correct only the centre of the visual field and leave the periphery somewhat myopic, (ii) outdoor activity or equivalent temporary increase in illuminance, (iii) pharmacological intervention of retinal growth signals that are transmitted to the underlying sclera. Options (i) and (ii) can be used without risks although there is still room for improvement of the variables. Option (iii) has re-entered a new phase of orientation with new searches for candidate targets after previous testing with muskarinic antagonists (pirenzepine) in children did not enter phase 3 level. If myopia is outside the range over which it is visually controlled by emmetropisation (in the case of high and pathological myopias), in principle the possibility exists to improve the mechanical stability of the sclera pharmacologically. However, there is still a need for more research. Up to now, the mechanical weakness of the sclera in highly mopyic eyes is surgically stabilised by "scleral buckling". However, these procedures have found limited acceptance since the effects were not very reliable. In 40 - 50 % of the cases of high myopia, degenerative processes are found in the retina which can be seen as consequence of the mechanical tension in the fundus, but may also be indepedent of this factor (no significant correlation with axial length!). In part they can be slowed down by intravitreal anti-VEGF therapy. A long-term study from Denmark has shown that most patients with myopia of between 6-9 dpt during puberty reach retirement age without disabling visual loss.

Detection of behavioral alterations and learning deficits in mice lacking synaptophysin.

The integral membrane protein synaptophysin is one of the most abundant polypeptide components of synaptic vesicles. It is not essential for neurotransmission despite its abundance but is believed to modulate the efficiency of the synaptic vesicle cycle. Detailed behavioral analyses were therefore performed on synaptophysin knockout mice to test whether synaptophysin affects higher brain functions. We find that these animals are more exploratory than their wild type counterparts examining novel objects more closely and intensely in an enriched open field arena. We also detect impairments in learning and memory, most notably reduced object novelty recognition and reduced spatial learning. These deficits are unlikely caused by impaired vision, since all electroretinographic parameters measured were indistinguishable from those in wild type controls although an inverse optomotor reaction was observed. Taken together, our observations demonstrate functional consequences of synaptophysin depletion in a living organism.

The pupillary light reflex pathway: cytoarchitectonic probabilistic maps in hemianopic patients.

OBJECTIVE: The anatomy of the human pupillary light reflex (PLR) pathway is a matter of debate. The aim of this study was twofold: namely, to investigate the association of a relative afferent pupillary defect (RAPD) in acquired suprageniculate lesions with the location and extent of the cerebral lesions. Further, we suggest a new strategy of lesion analysis by combining established techniques with the stereotaxic probabilistic cytoarchitectonic atlas developed by the Jülich group. METHODS: Twenty-three patients with homonymous visual field defects participated in this study. The RAPD was quantified clinically by two independent examiners with graded neutral density filters (swinging flashlight test). Using MRI in each individual, cerebral regions commonly affected in patients with a RAPD but spared in patients without a RAPD were determined and subsequently assessed by using cytoarchitectonic probabilistic maps. RESULTS: A RAPD was present in 10/23 patients. Comparison of patients showing a RAPD vs those not showing a RAPD revealed that a region including the course of the optic radiation at its early beginning in the temporal white matter is commonly associated with a RAPD. CONCLUSIONS: It was demonstrated that the pupillary light reflex (PLR) depends on the input of suprageniculate neurons, thus supporting the involvement of a cortical pathway also. The site of integration of cortical signals in relation to the PLR into the pupillomotor pathway may be located suprageniculately in the vicinity of the lateral geniculate nucleus. Moreover, the suggested combination of established lesion analysis techniques with the probabilistic cytoarchitectonic atlas turned out to be a very helpful amelioration of stroke data analyses.

Accommodation behaviour during prey capture in the Vietnamese leaf turtle ( Geoemyda spengleri).

Vietnamese leaf turtles ( Geoemyda spengleri) were tested for their ability to focus on prey objects at various distances. Accommodation was continuously measured by infrared photoretinoscopy. All animals investigated during this study showed a surprisingly high precision of accommodation over a range of over 30 D. Measured accommodation matched the target distance accurately for distances between 3 and 17 cm. The turtles switched between independent and coupled accommodation in the two eyes. Independent accommodation was observed when the turtles inspected their environment visually without a defined object of interest. Coupled accommodation was only observed during binocular prey fixation. When a turtle aimed at a target, the symmetrical focus of both eyes persisted even if vision was totally blocked in one eye or altered by ophthalmic lenses. This suggests that the eyes were linked by internal neuronal mechanisms. The pupil of the eye responded clearly to changes in ambient light intensity. A strong decrease in pupil size was also observed when the eye was focused on a close target. In this case, the constriction of the pupil probably aids in the deformation of the eye lens during near-accommodation.

Variations in the off-axis refractive state in the eye of the Vietnamese leaf turtle (Geoemyda spengleri).

Lower-field myopia has been described for various vertebrates as an adaptation that permits the animal to keep the ground in focus during foraging, and, at the same time, to look out for distant objects, such as predators, in the upper visual field. Off-axis measurements with infrared photoretinoscopy in the eye of Geoemyda spengleri revealed a constant refractive state in the horizontal plane of the visual field but variable refraction in the vertical plane. In the three turtles investigated, the refractions increased continuously from the ventral to the dorsal visual field over a range of 35, 40 and 56 D, respectively. While this finding confirms the presence of an adaptive change of the refractive state equivalent to lower field myopia, subsequent measurements with a rotated retinoscope showed that at least part of the variation in the ventral field was attributed to astigmatism. The reason for this astigmatism is unknown. Anatomical investigation of the retina revealed that the constant refractive values in the horizontal plane corresponded to a stripe of increased ganglion cell density. A maximum density of 4,200 ganglion cells mm(-2) was counted in the centre of this visual streak.

Changes in contrast sensitivity induced by defocus and their possible relations to emmetropization in the chicken.

PURPOSE: To test whether the level of contrast adaptation (CA) relates to refractive development in the chicken. (CA refers to a spatial frequency-selective increase of suprathreshold contrast sensitivity after exposure to low-contrast patterns). METHODS: CA was determined in individual chicks by comparing their optomotor gain in response to drifting low-contrast stripe patterns before and after treatment with spectacle lenses. The amount of CA was compared with the loss of contrast predicted from defocus at the tested spatial frequency. The reversion of CA and recovery from deprivation myopia were studied while the retinal image features were controlled by forcing the animals to watch spatially filtered digital video clips. RESULTS: CA was induced by wearing positive and negative lenses for 1.5 hours, both without and with cycloplegia, but was less pronounced in the case of positive lenses when accommodation was intact. The amount of CA at a tested spatial frequency was predicted from the loss of contrast calculated from the modulation transfer function for a defocused optical system. Watching low-pass-filtered video clips induced deprivation myopia and inhibited recovery from it. It also prevented the reversal of CA that was previously induced by deprivation. Both recovery from deprivation myopia and recovery from CA occurred with sharp video clips, although less so than with normal visual exposure. CONCLUSIONS: CA changes with retinal image sharpness and occurs even when accommodation is intact. Because CA correlates with myopia induced by frosted occluders, negative lenses, and low-pass-filtered video clips, and its reversal correlates with recovery from myopia, it is possible that shifts in CA may represent a signal related to refractive error development.

Pineal control of the dopamine D2-receptor gene and dopamine release in the retina of the chicken and their possible relation to growth rhythms of the eye.

Retinal dopamine (DA) and the DA D2-receptor have been implicated in the development of "deprivation myopia", induced by frosted eye occluders. We have studied the changes in D2-mediated dopaminergic transmission in the retina, their possible relations to eye growth rhythms and myopia, and their control by the pineal gland. (1) We found that the sensitivity of eye growth to retinal image degradation varied over the day. Intermittent periods of normal vision inhibited deprivation myopia more if they occurred in the evening than in the morning. (2) Diurnal growth rhythms in both eyes interacted even though it was previously shown that both deprivation myopia and the accompanying changes in retinal DA release can be monocularly induced. (3) The D2-receptor mRNA concentration in the retina showed no systemic diurnal changes and was not affected by deprivation myopia, but was increased after 2 days in darkness. Since DA release varies over the day, the gain of dopaminergic transmission may also vary, which could explain the observation described in (1) above. (4) Depletion of retinal DA by intravitreal application of reserpine, which lowers DA content severely, had little effect on D2-receptor mRNA concentration. (5) Selective illumination of the pineal gland reduced the D2-receptor mRNA content in the retina to a similar level to full illumination, indicating that the pineal gland controls the D2-receptor mRNA content in the retina. The pineal also controlled DA release in the retina. These results show that the pineal has a surprisingly large influence on both the retinal DA receptor gene transcription and DA release. It can probably control the gain of dopaminergic transmission in the retina and deprivation myopia and mediate the interactions of the growth rhythms in both eyes.

Laboratory, clinical, and kindergarten test of a new eccentric infrared photorefractor (PowerRefractor).

PURPOSE: Photorefraction is a convenient way to determine refractive state from a distance. It is, therefore, useful for measuring infants and noncooperative subjects. However, its reliability (or precision) and accuracy (or validity) has been questioned. In a study in subjects without cycloplegia, we have tested whether, after complete automatization, eccentric photorefraction at a 1-m distance can be as reliable as a common autorefractor. METHODS: In a laboratory study of 15 student subjects without the use of cycloplegia (30 eyes, refractive errors ranging from -6 D to +6 D), age 25 to 31 years, the photorefractive measurements were compared with spectacle prescriptions. In a clinical study, photorefraction, autorefraction, and subjective refraction were performed in 40 patients without cycloplegia (refractive errors ranging from -4 D to +4 D), most of them with various ocular pathologies. Subjective refractions were obtained by an experienced clinical ophthalmologist but were not accessible to the examiner who used the two refractors. Visual acuity was 20/20 or better except for five subjects. Ages ranged from 6 to 75 years. In the kindergarten screening study, 108 children aged 3 to 6 years were screened for refractive errors. RESULTS: In the laboratory study, it was found that the mean difference between spectacle prescription and PowerRefractor measurements was < 0.6 D for spheres and below 0.4 D for cylinders. In the clinical study, data were obtained by all three procedures in 78 eyes. The photorefractor and the autorefractor performed similarly for spheres (mean absolute dioptric difference between refractor and subjective measure: 0.593 D and 0.696 D) and cylinders (mean absolute dioptric differences: 0.399 D and 0.389 D). However, the photorefractor was superior with regard to the measurement of the magnitude and axis of astigmatism (mean weighted difference between objective and subjective axis 0.644 D and 0.769 D, respectively). In the kindergarten study, it was found that the PowerRefractor was very convenient to handle. The autorefractor measured more myopic refractions than the PowerRefractor (mean of the left eyes 0.11 +/- 1.1 D vs. 0.62 +/- 0.53 D, p < 0.001). There was no indication that the PowerRefractor failed to detect hyperopia, because all but one child with more than 2 D of hyperopia measured with autorefractor (n = 7) was also hyperopic with the PowerRefractor. Furthermore, presenting an interesting fixation target at a 3-m distance did not cause more hyperopic refractions, indicating that the camera of the PowerRefractor at a 1-m distance was not a significant stimulus to accommodation. CONCLUSIONS: The PowerRefractor was shown to have comparable or slightly better reliability and accuracy than a modern autorefractor; however, it has major advantages over current autorefractors in that it is faster, measures both eyes at once, and gives interpupillary distance, pupil size, and information on the alignment of the eyes at the same time.

Developmental compensation of imposed astigmatism is not initiated by astigmatic accommodation in chickens.

PURPOSE: It is not clear whether emmetropization is confined to spherical refractive errors, or whether astiqmatic errors are also corrected via visual feedback. Experimental results from the animal model of the chicken are equivocal since compensation of imposed astimatic defocus was found in some but not all studies. Astigmatism could only be compensated by changes in the geometry of the cornea or lens. One has tested whether astigmatic spectacle lenses induce astigmatic accommodation as a possible first step of long-lasting compensation. METHODS: Thirty-five chickens were treated with cylinder lenses (+3/0D or -3/0D) for 5 h. Refractions were determined at 1.38 m distance without cycloplegia in hand-held chicks before attaching the lenses, with the lenses on (0 h), and after 3 and 5 h, and after removal of the lenses. Spheres (S), cylinders (C) and axes (A) were determined using infrared photoretinocopy in three axes (the 'PowerRefractor', equipped with a 135 mm lens). RESULTS: (1) The performance of the 'PowerRefractor' was tested in the chickens with trial lenses and gave correct refractions. (2) Astigmatic trial lenses induced refractive errors as expected from their powers in the case of +3/0D lenses: (S) +3.26 +/- 0.93D, (C) -3.45 +/- 0.87D). In the case of -3/0D lenses, slightly more hyperopic spheres were induced (refractions (S) +4.5 +/- 0.48D) but the cylinders were still as expected (-3.25 +/- 0.49D). The axes of astigmatism were correctly reproduced, since rotating the lenses changed the axes of the induced cylinders as expected. (3) Neither after 3 nor after 5 h of lens wear were there significant changes in the axes or the magnitude of astigmatism. Directly after removal of the lens, the refractions did not differ from their start-up values (with +3/0D lenses: (S) +3.31 +/- 1.05D vs. +3.22 +/- 0.76D, (C) -1.19 +/- 1.77D vs. -0.65 +/- 0.94D, (A) 96 +/- 49 vs. 113 +/- 45 deg; with -3/0D lenses: (S) 2.63 +/- 1.12D vs. 2.97 +/- 0.94D, (C) -1.11 +/- 1.15D vs. -0.53 +/- 0.56D, (A) 78 +/- 24 vs. 131 +/- 35 deg). CONCLUSIONS: The most intuitive mechanism for compensation of astigmatic refractive errors, astigmatic accommodation, could not be demonstrated in chickens. In light of this finding, it seems unlikely that a visually controlled mechanism is operating during development to reduced astigmatism by changing corneal or lenticular growth.

Changes in retinal and choroidal gene expression during development of refractive errors in chicks.

PURPOSE: During growth, the retina analyzes the projected image to achieve a close match between eye length and focal length. Because the messengers released by retina and choroid are largely unknown, genes that are differently expressed in response to changes in the retinal image were identified. In addition, because glucagon may be important in the visual control of eye growth, the transcript levels of proglucagon were studied. METHODS: Reverse transcription-polymerase chain reaction differential display was used to identify genes that were differentially expressed in chick eyes that were deprived of sharp vision or treated with positive or negative lenses. Differences were analyzed through sequencing and database searches and confirmed by Northern blot analyses. RESULTS: Combining 40 and 33 arbitrary primers with 3 oligo-dT-primers, approximately 48% and 40% of the retinal and choroidal mRNAs were screened, respectively. Twelve differences were detected in retinal tissue and five in choroidal tissue after 6 to 24 hours of exposure to defocus. Only one of 10 sequenced products could be identified as cytochrome-c oxidase, subunit I. Northern blot analysis confirmed its twofold upregulation after positive lens wear and also changes in four other unknown genes. Finally, it was shown that retinal glucagon mRNA content increased after treatment with positive lenses. CONCLUSIONS: Visual conditions that induce refractive errors produce changes in gene expression in retina and choroid within 1 day. In line with previous immunohistochemical data, it was found that the amount of glucagon mRNA was upregulated during wearing of positive lenses.

Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick.

Atropine has previously been found to suppress visually induced myopia both in animals and humans. The mechanism of its action is unclear. We have studied its retinal effects in an in vitro preparation, using the retina-pigment epithelium-choroid complex of the chick eye. In vivo, deprivation myopia was induced by translucent goggles. Atropine solution was injected into the vitreous at two-day intervals. Dopamine release from the retina following atropine injection in vivo and from the in vitro retina preparation was quantified by HPLC-EC. In vitro preparations of the isolated chick retina-pigment epithelium-choroid were superfused with atropine. Light-induced potentials (local ERG), slow standing potentials from the retinal pigment epithelium/neural retina, and extracellular potassium concentrations were recorded. In line with previous findings, intravitreal injections of atropine (25 microg, 250 microg) reduced deprivation myopia in a dose-dependent manner. Atropine increased the release of the neurotransmitter dopamine into the superfusate in vitro at 100-500 microM and into the vitreous in vivo at 250 microg. Before an increase was measured in the vitreous, the retinal dopamine content was elevated. In concentrations equivalent to the intravitreal concentration to suppress myopia in vivo (200-800 microM), atropine induced spreading depression (SD) in the in vitro preparation. In contrast, muscarinic agonists, acetylcholine and pilocarpine, did not induce SD. Atropine reduced the ERG b- and d-wave, led to damped oscillations of RPE potentials, and reversed the ERG c-wave. Atropine suppressed myopia only at doses at which severe nonspecific side effects were observed in the retina. Atropine seems to intrude massively into the vital functions of the retina as indicated by the occurrence of SD. We conclude that atropine, by inducing SD, boosts neurotransmitter release from cellular stores, which may cancel out a presumed retinal signal that controls eye growth and through this, myopia.

Visually induced changes in components of the retinoic acid system in fundal layers of the chick.

Eye growth is visually regulated via messengers that are released from the retina. The retina involves a yet unknown algorithm to analyse the projected image so that the appropriate growth rates for the back of the eye are ensured. One biochemical candidate that could act as a growth controller, is retinoic acid (RA). Previous work (Seko, Shimokawa and Tokoro, 1996; Mertz et al., 1999) has shown that retinal and choroidal RA levels are indeed predictably changed by visual conditions that cause myopia or hyperopia, respectively. We have studied in which fundal tissues aldehyde dehydrogenase-2 (AHD2) and retinaldehyde dehydrogenase-2 (RALDH2), enzymes involved in RA synthesis, are expressed and at which levels the effects of vision on RA levels may be controlled. Using Northern blot analysis, we have found that the retinal mRNA level of the AHD2 is up-regulated after 3 days of treatment with negative lenses (negative lenses place the image behind the retina). The abundance of the retinal mRNA of a RA receptor, RAR-beta, was up-regulated already after 6 hr of treatment with positive lenses (positive lenses place the image in front of the retina). The up-regulation persisted for at least 1 week. Finally, we have studied the effects of an inhibitor of RA synthesis, disulfiram, on the visual control of eye growth. We found inhibition of myopia as induced by frosted goggles ('deprivation myopia') but no significant inhibitory effects on refractive errors induced by +7D or -7D lenses. Our results are in line with the hypothesis that RA may play a role in the visual control of eye growth. The RA system differs from a number of other candidates (dopamine, cholinergic agents, opiates) in that it distinguishes between positive and negative defocus, similar to the immediate early gene ZENK (Stell et al., 1999). The exact time kinetics of the changes have still to be worked out since it is possible that the changes in RA relate to already occurring changes in growth rather than to initial steps of the signaling cascade.