Role of 7-methylxanthine in myopia prevention and control: a mini-review.

Myopia is becoming increasingly common. By 2050 around 10% of the world's population is expected to be highly myopic (<-5 diopters) and therefore particularly at risk of suffering from sight-threatening complications. Currently used myopia control treatments, such as multifocal soft contact lenses or spectacle lenses, orthokeratology, and atropine eyedrops, either do not completely arrest myopia progression or are associated with significant ocular and possibly systemic side effects. A new candidate for pharmaceutical control of myopia progression and excessive eye elongation, the non-selective adenosine antagonist 7-methylxanthine (7-MX), appears to be non-toxic and effective in reducing myopia progression and axial eye growth in experimental and clinical studies. The latest findings regarding 7-MX for myopia control and evaluate its potential as a supplement to existing treatment options were reviewed.

Oral administration of caffeine metabolite 7-methylxanthine is associated with slowed myopia progression in Danish children.

PURPOSE: Myopia is associated with an increased risk of permanent vision loss. The caffeine metabolite 7-methylxanthine (7-MX), licensed in Denmark since 2009 as a treatment to reduce the rate of childhood myopia progression, is the only orally administered therapy available. The purpose of the current study was to assess the rate of myopia progression in children taking 7-MX. METHODS: Longitudinal cycloplegic refraction and axial length data for 711 myopic children from Denmark treated with varying doses of oral 7-MX (0-1200 mg per day) were analysed using linear mixed models. RESULTS: The median age at baseline was 11.1 years (range 7.0 -15.0 years). Children were followed for an average of 3.6 years (range 0.9-9.1 years) and the average myopia progression was 1.34 dioptres (D) (range -6.50 to +0.75 D). Treatment with 7-MX was associated with a reduced rate of myopia progression (p<0.001) and axial elongation (p<0.002). Modelling suggested that, on average, an 11-year-old child taking 1000 mg 7-MX daily would develop -1.43 D of myopia over the next 6 years, compared with -2.27 D if untreated. Axial length in this child would increase by 0.84 mm over 6 years when taking a daily dose of 1000 mg of 7-MX, compared with 1.01 mm if untreated. No adverse effects of 7-MX therapy were reported. CONCLUSIONS: Oral intake of 7-MX was associated with reduced myopia progression and reduced axial elongation in this sample of myopic children from Denmark. Randomised controlled trials are needed to determine whether the association is causal.

Effects of 7-Methylxanthine on Deprivation Myopia and Retinal Dopamine Release in Chickens.

INTRODUCTION: Intake of 7-methylxanthine (7-MX), an adenosine receptor (AR) antagonist, has been shown to inhibit school myopia in children and deprivation myopia in rhesus monkeys, but the underlying mechanisms are not known. Also retinal dopamine seems to be involved in the control of eye growth, and in the brain, ARs and dopamine receptors interact widely by heteromerization. We have studied whether 7-MX can inhibit deprivation myopia also in chickens and whether inhibition may involve the retinal dopamine system. METHODS: 7-MX was applied by either tube-feeding (100 µg/g body weight, twice a day) or intravitreal injection (12.5 µg, every other day). Forty-eight 2-week-old chicks wore unilateral diffusers and were randomly assigned to either the tube-feeding group (involving 7-MX, vehicle [xanthan gum], or no feeding, for 13 days) or the intravitreal injection group (involving 7-MX, vehicle, or DMSO, for 8 days). Refractions (REs), ocular biometry (AL, VCD), and scleral and choroidal thickness (ChT) were measured before and after treatment. Dopamine and dihydroxyphenylacetic acid (DOPAC) content were determined in retina and vitreous by HPLC at the end of the experiments. RESULTS: No matter how 7-MX was applied, it did not inhibit deprivation myopia in chicks. No significant differences were observed in RE, VCD, AL, and scleral fibrous layer thickness. Feeding 7-MX produced more choroidal thinning in the open contralateral eye compared to control eyes in the vehicle-fed group (-40 ± 14 vs. -1 ± 7 µm, unpaired t test, p < 0.05). DOPAC and dopamine concentration in vitreous and DOPAC concentration in retina did not change with 7-MX. Vitreal dopamine content was significantly decreased in deprived eyes in the groups fed with the vehicle xanthan gum (paired t test, p < 0.01) but not in 7-MX-treated eyes, perhaps indicating a small effect of 7-MX on dopamine. CONCLUSIONS: In our study, 7-MX had no effect on DM in chicks and only minor effects on ChT and retinal dopamine. It remains unclear whether 7-MX inhibits myopia through a retinal mechanism or whether it acts directly on choroid and sclera. In the latter case, the finding that myopia is suppressed in mammals but not birds might be explained by differences in scleral structure.

Characteristics of Corneal Biomechanics in Chinese Preschool Children With Different Refractive Status.

PURPOSE: To investigate the characteristics of corneal biomechanics in Chinese preschool children with different refractive status. METHODS: Study participants were 108 Chinese children (216 eyes) aged 4 to 6 years with a spherical equivalent refraction between -9.00 and +9.00 diopters (D). Cycloplegic refraction was measured using an autorefractor, axial length using an IOL Master (Zeiss, Oberkochen, Germany), and corneal biomechanical metrics and corneal power using an ultra-high-speed camera (Corvis ST; Oculus, Wetzlar, Germany) and Pentacam (Oculus; Menlo Park, CA). Differences in corneal biometry and biomechanical characteristics among myopia, emmetropia, and hyperopia eyes were analyzed by SPSS 17.0. RESULTS: The spherical equivalent refraction was significantly positively correlated with the stiffness parameter at the first applanation (SP-A1, r = 0.22, P < 0.01) and corneal velocity at the second applanation (A2 velocity, r = 0.25, P < 0.001), whereas it was negatively correlated with the peak distance (r = -0.32, P < 0.001) and deformation amplitude ratio (DA ratio, r = -0.34, P < 0.001). In the hyperopia, emmetropia, and myopia groups, the SP-A1 successively decreased (108.70 ± 22.93 vs. 100.50 ± 18.98 vs. 97.97 ± 18.91, P < 0.01), whereas the peak distance progressively increased (4.39 ± 0.32 vs. 4.56 ± 0.30 vs. 4.63 ± 0.34 mm, P < 0.001). In the same order of groups, an increasing trend was found for the axial length (21.11 ± 0.76 vs. 22.39 ± 0.72 vs. 24.09 ± 1.37 mm, P < 0.001), central anterior chamber depth (CACD, 3.04 ± 0.41 vs. 3.21 ± 0.33 vs. 3.37 ± 0.40 mm, P < 0.001) and flat meridian keratometry (K1, 41.92 ± 1.59 vs. 42.73 ± 1.39 vs. 42.98 ± 1.60 D, P < 0.001). Central corneal thickness significantly decreased in the same order of groups (565.46 ± 33.22 vs. 551.97 ± 24.66 vs. 543.36 ± 37.74 µm, P < 0.001). CONCLUSIONS: Corneal stiffness is reduced in myopia and increased in hyperopia compared with emmetropia in children aged 4 to 6 years. Corneal biometry and biomechanical characteristics in preschool children seem to depend on refractive status.

IMI - Interventions Myopia Institute: Interventions for Controlling Myopia Onset and Progression Report.

Myopia has been predicted to affect approximately 50% of the world's population based on trending myopia prevalence figures. Critical to minimizing the associated adverse visual consequences of complicating ocular pathologies are interventions to prevent or delay the onset of myopia, slow its progression, and to address the problem of mechanical instability of highly myopic eyes. Although treatment approaches are growing in number, evidence of treatment efficacy is variable. This article reviews research behind such interventions under four categories: optical, pharmacological, environmental (behavioral), and surgical. In summarizing the evidence of efficacy, results from randomized controlled trials have been given most weight, although such data are very limited for some treatments. The overall conclusion of this review is that there are multiple avenues for intervention worthy of exploration in all categories, although in the case of optical, pharmacological, and behavioral interventions for preventing or slowing progression of myopia, treatment efficacy at an individual level appears quite variable, with no one treatment being 100% effective in all patients. Further research is critical to understanding the factors underlying such variability and underlying mechanisms, to guide recommendations for combined treatments. There is also room for research into novel treatment options.

The Adenosine Receptor Antagonist, 7-Methylxanthine, Alters Emmetropizing Responses in Infant Macaques.

Purpose: Previous studies suggest that the adenosine receptor antagonist, 7-methylxanthine (7-MX), retards myopia progression. Our aim was to determine whether 7-MX alters the compensating refractive changes produced by defocus in rhesus monkeys. Methods: Starting at age 3 weeks, monkeys were reared with -3 diopter (D; n = 10; 7-MX -3D/pl) or +3D (n = 6; 7-MX +3D/pl) spectacles over their treated eyes and zero-powered lenses over their fellow eyes. In addition, they were given 100 mg/kg of 7-MX orally twice daily throughout the lens-rearing period (age 147 ± 4 days). Comparison data were obtained from lens-reared controls (-3D/pl, n = 17; +3D/pl, n = 9) and normal monkeys (n = 37) maintained on a standard diet. Refractive status, corneal power, and axial dimensions were assessed biweekly. Results: The -3D/pl and +3D/pl lens-reared controls developed compensating myopic (-2.10 ± 1.07 D) and hyperopic anisometropias (+1.86 ± 0.54 D), respectively. While the 7-MX +3D/pl monkeys developed hyperopic anisometropias (+1.79 ± 1.11 D) that were similar to those observed in +3D/pl controls, the 7-MX -3D/pl animals did not consistently exhibit compensating myopia in their treated eyes and were on average isometropic (+0.35 ± 1.96 D). The median refractive errors for both eyes of the 7-MX -3D/pl (+5.47 D and +4.38 D) and 7-MX +3D/pl (+5.28 and +3.84 D) monkeys were significantly more hyperopic than that for normal monkeys (+2.47 D). These 7-MX-induced hyperopic ametropias were associated with shorter vitreous chambers and thicker choroids. Conclusions: In primates, 7-MX reduced the axial myopia produced by hyperopic defocus, augmented hyperopic shifts in response to myopic defocus, and induced hyperopia in control eyes. The results suggest that 7-MX has therapeutic potential in efforts to slow myopia progression.

Effect of 7-methylxanthine on human retinal pigment epithelium cells cultured in vitro.

Purpose: To evaluate the effects of 7-methylxanthine (7-MX) on the growth of human retinal pigment epithelium (RPE) cells and to observe the changes in the expression of adenosine receptors (ADORs) in RPE cells upon 7-MX treatment. Methods: Human RPE cells (monolayer at about 80% confluence) were cultured in vitro in the presence or absence of 7-MX. Cell proliferation was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cell cycle distribution and apoptosis level were analyzed with flow cytometry. Quantitative PCR and immunofluorescence assay were used to examine the mRNA and protein expression of ADORs. Results: 7-MX at low concentrations had no effect on the proliferation of RPE cells, whereas 100 µmol/l 7-MX slightly decreased cell proliferation at 48 h but without a statistically significant difference. The 7-MX treatment was performed at the low concentration of 10 µmol/l in the following experiments. The proportion of RPE cells in the G1 stage was slightly increased at 24 h (p=0.035) but decreased at 48 h (p=0.0045) upon 7-MX treatment; and the proportion was restored to normal at 72 h. No statistically significant change in apoptosis levels was found in RPE cells cultured with 7-MX. The expression of ADORA1, ADORA2A, and ADORA2B in RPE cells was inhibited by 7-MX treatment at 48 h, while the expression levels appeared to rebound at 72 h. Conclusions: 7-MX has little effect on the proliferation or apoptosis level of human RPE cells; however, in short-term treatment, 7-MX disturbs the proportion of cells in the G1 stage and inhibits the expression of ADORA1, ADORA2A, and ADORA2B.

All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta.

PURPOSE: All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. METHODS: HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 µmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence. RESULTS: After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARß), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK. CONCLUSIONS: ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta.

Effect of day length on eye growth, myopia progression, and change of corneal power in myopic children.

OBJECTIVE: Because of the northern location of Denmark, the length of the day over the year varies from 7 to 17.5 hours. Experimental and clinical results suggest that the development of myopia may be related to ambient light exposure. The purpose of current study was to investigate whether axial eye growth, myopia progression, or corneal power change in Danish myopic children varies with the length of the day. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred thirty-five children 8 to 14 years of age found to have myopia during screening for a clinical trial (ClinicalTrial.gov identifier, NCT00263471; accessed December 6, 2005). All children found to have any value of spherical equivalent that was myopic (<0 diopters [D]) at the first of 2 visits were included. METHODS: Cycloplegic refraction was measured using an autorefractor, axial eye length, and corneal power using an automatic combined noncontact partial coherence interferometer and keratometer. The accumulated number of daylight hours during the measurement period was calculated for each participant using an astronomical table. MAIN OUTCOME MEASURES: Change over 6 months in axial length, refraction, and corneal power. RESULTS: Accumulated hours of daylight ranged from 1660 to 2804 hours. Significant correlations were found between hours of daylight and eye elongation (P = 0.00), myopia progression (P = 0.01), and corneal power change (P = 0.00). In children with an average of 2782 ± 19 hours of daylight, axial eye growth was 0.12 ± 0.09 mm, myopia progression was 0.26 ± 0.27 D, and corneal power change was 0.05 ± 0.10 D per 6 months, whereas in children with an average of 1681 ± 24 hours of daylight, axial eye growth was 0.19 ± 0.10 mm, myopia progression was 0.32 ± 0.27 D, and corneal power change was -0.04 ± 0.08 D per 6 months. CONCLUSIONS: Eye elongation and myopia progression seem to decrease in periods with longer days and to increase in periods with shorter days. Children should be encouraged to spend more time outside during daytime to prevent myopia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Effects of 7-methylxanthine on form-deprivation myopia in pigmented rabbits.

AIM: To determine the effect of 7-methylxanthine (7-MX) on the posterior sclera of form-deprivation myopia (FDM) in pigmented rabbits. METHODS: Sixteen pigmented rabbits were monocularly deprived (MD) by suturing the right eyelids after natural eye opening (ten-day old) for a period of 30 days. Two groups of pigmented rabbits were fed either 7-MX (30 mg per kg body weight; n=8) or vehicle control (saline equal volume with 7-MX; n=8). Ocular refractions, axial lengths and body weights were measured at the start and the end of the experiment 30 days later. Electron microscopy was used to measure and determine the collagen fibril diameters in the posterior pole of sclera. RESULTS: In vehicle control MD pigmented rabbits, 30 days of MD produced -1.10D±0.78D of myopia and the axial length increased 0.51mm±0.09mm. In MD pigmented rabbits fed with 7-MX, 30 days of MD induced only -0.21D±0.11D of myopia and the axial length increased 0.07mm±0.10mm. There was significant change in axial length of vehicle control MD pigmented rabbits (13.11mm±0.19mm versus 12.60mm±0.06mm; P=0.03). The changes in refraction and axial length of two MD groups' contralateral eyes during the 30 days were not significantly different (2.75D±0.27D versus 2.75D±0.35D, P>0.05; 12.60mm±0.06mm versus 12.45mm±0.14mm, P>0.05). The weights of the two groups pigmented rabbits had no significant changes (187g±22.1g versus 189g±19.3g, P>0.05). The diameter of scleral collagen fibers increased in both eyes of 7-MX treated pigmented rabbits. There was significant difference in collagen fibril diameters of inner layer (111.34nm±28.30nm versus 94.80nm±27.52nm, P=0.002) and outer layer (167.92nm±55.82 nm versus 144.04 nm±47.02nm, P=0.016) in the posterior sclera between the myopic eyes of vehicle control MD group and contralateral eyes of 7-MX treated MD group. CONCLUSION: 7-MX appears to prevent FDM in pigmented rabbits by remodeling the posterior sclera.

A retrospective study: form-deprivation myopia in unilateral congenital ptosis.

BACKGROUND: The aim of this retrospective study was to investigate the relationship between unilateral congenital ptosis in patients older than eight years and their refractive state and spherical equivalent refraction (SER). METHODS: The study involved a review of the clinical records of 85 patients admitted to the First Affiliated Hospital, Sun Yat-sen University between 1998 and 2010 with unilateral congenital ptosis. The average age was 16.83 years (nine to 27 years). The patients were classified into mild (27 cases), moderate (37 cases) or severe (21 cases) ptosis according to the degree of the droopy eyelid covering the cornea. The fellow eyes served as controls. RESULTS: In 85 eyes with unilateral ptosis, the frequency of myopia (SER of -0.50 D or more myopia) was significantly higher than in the fellow eye (47 versus 32, p = 0.031). The frequency of myopia in eyes with severe unilateral ptosis was significantly higher than in the fellow eyes (16 versus 7, p = 0.012), whereas there were no significant differences in patients with mild (15/27 versus 13/27, p = 0.79) or moderate (16/37 versus 12/37, p = 0.47) unilateral ptosis. Similarly, the SER was significantly more myopic in eyes with severe ptosis compared with the fellow eye (-1.37 D versus -0.85 D, p = 0.01), whereas no significant differences were found in patients with mild or moderate unilateral ptosis. CONCLUSIONS: The results showed a higher frequency of myopia and more myopic SER in eyes with severe unilateral ptosis compared with the fellow eye. The myopia found in eyes with unilateral ptosis might be caused by a mechanism similar to that resulting in myopia among animals subjected to form deprivation. It is important to pay attention to possible refractive error in patients with unilateral ptosis. Surgical correction of unilateral ptosis at an early age is recommended.

Expression of adenosine receptors in human retinal pigment epithelium cells in vitro.

BACKGROUND: Adenosine receptors (ADORs) have been reported to play a role in experimental myopia. This study aimed to determine the distribution of ADORs in human retinal pigment epithelium (RPE) cells cultured in vitro. METHODS: Human RPE cells (cell line D407) were cultured in vitro. ADOR mRNA in RPE was detected by reverse transcription polymerase chain reaction. ADOR protein expression in RPE was confirmed by Western blotting analysis of cell lysates. Confocal fluorescence microscopy was used to study the subcellular distribution of ADORs. RESULTS: All four subtypes of ADORs mRNA and protein were expressed in human RPE. This was confirmed by Western blotting analysis. The ADOR subtypes were differently distributed within the cells. ADORA1 was expressed in nucleus, perinucleus and cytoplasm of RPE. ADORA2A was concentrated mainly in one side of the perinucleus and cytoplasm of RPE. ADORA2B was strongly expressed in the nucleus, perinucleus and the cytoplasm, and ADORA3 was expressed weakly in the cytoplasm of RPE. CONCLUSIONS: ADORs are expressed in human RPE. The different distribution at the subcellular level suggests different functions of ADOR subtypes.

Effects of 7-methylxanthine on the sclera in form deprivation myopia in guinea pigs.

PURPOSE: The aim of this study was to determine the effect of the adenosine receptor antagonist 7-methylxanthine (7-MX) on form deprivation myopia in 3-week-old guinea pigs. METHODS: Two groups of 3-week-old guinea pigs were subjected to monocular deprivation (MD) using a diffuser and fed either 7-MX (300 mg/kg body weight; n = 7) or vehicle control (saline at an equal volume to 7-MX; n = 7). A control group (n = 6) was not subjected to form deprivation. Ocular refraction, axial length and body weight were measured at the start and after 21 days. The thickness of the posterior sclera was measured by light microscopy and the collagen fibril diameter in the inner, middle and outer layers of the sclera was measured by electron microscopy. RESULTS: In the vehicle control group, 21 days of MD produced significant amounts of myopia, axial elongation, thinning of the posterior sclera and thinning of the median collagen fibril diameter in the posterior sclera relative to the contralateral eyes. In the guinea pigs fed with 7-MX, however, form deprivation produced significantly less myopia and axial elongation compared with vehicle control animals. The 7-MX-treated animals exhibited a thickening of the posterior sclera in both the MD eye and the contralateral eye. In the 7-MX-treated animals, the median collagen fibril diameter in the posterior sclera was not reduced by form deprivation. CONCLUSIONS: Treatment with 7-MX appears to not only decrease the amount of myopia by around 50% and eliminate the eye elongation induced by form deprivation in guinea pigs, but also to prevent form deprivation myopia-related scleral changes, such as thinning of the sclera and thinning of the collagen fibril diameter in the posterior sclera.

Adenosine receptor protein changes in guinea pigs with form deprivation myopia.

PURPOSE: Recent results have shown that treatment with the non-selective adenosine antagonist 7-methylxanthine (7-MX) reduces the development of form deprivation myopia (FDM) in guinea pigs. The aims of this study were to identify the presence of adenosine receptors (AdoRs) in the eye wall of the guinea pig and to determine their possible changes during form deprivation. METHODS: Three-week-old guinea pigs were monocularly treated with a translucent lens to induce FDM. After 21 days, samples were taken from the posterior eye wall and examined with immunofluorescence confocal microscopy for the presence of AdoRA1, AdoRA2A, AdoRA2B and AdoRA3 proteins. Western blot analysis was used to quantitate AdoRs in samples from the retina, choroids and sclera. RESULTS: All four subtypes of AdoR were expressed in the posterior wall of the guinea pig eye, although AdoRA3 only weakly. Twenty-one days after the induction of myopia, we observed a significant decrease in protein expression for AdoRA1 (- 25.5%) and an increase in protein expression for AdoRA2B (+ 66.7%) in the retina of FDM eyes. CONCLUSIONS: AdoRs of all subtypes are expressed in the retina, choroids and sclera in guinea pigs and may play a role in the regulation of eye growth. The changed pattern of AdoR expression during form deprivation confirms that pharmaceutical intervention targeting AdoRs may reduce myopia progression.

Distribution of adenosine receptors in human sclera fibroblasts.

PURPOSE: Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). METHODS: Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines and in the frozen human scleral sections. ADOR protein expression in HSF and human sclera was confirmed by western blot analysis of cell lysates. RESULTS: ADORs were expressed in both HSF and human sclera. This was confirmed by western blot. ADORA1 expression was concentrated in the nucleus. ADORA2A was concentrated mainly in one side of the cytoplasm, and ADORA2B was found both in the nucleus and the cytoplasm. ADORA3 was expressed weakly in the cytoplasm. CONCLUSIONS: All four subtypes of ADOR were found in HSF and may play a role in scleral remodeling.

Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study.

The adenosine antagonist 7-methylxanthine (7-mx) works against myopia in animal models. In a clinical trial, 68 myopic children (mean age 11.3 years) received either placebo or 7-mx tablets for 12 months. All participants subsequently received 7-mx for another 12 months, after which treatment was stopped. Axial length was measured with Zeiss IOL-Master and cycloplegic refraction with Nikon Retinomax at -6, 0, 12, 24, and 36 months. Axial growth was reduced among children treated with 7-mx for 24 months compared with those only treated for the last 12 months. Myopia progression and axial eye growth slowed down in periods with 7-mx treatment, but when the treatment was stopped, both myopia progression and axial eye growth continued with invariable speed. The results indicate that 7-mx reduces eye elongation and myopia progression in childhood myopia. The treatment is safe and without side effects and may be continued until 18-20 years of age when myopia progression normally stops.

Latanoprost eye drops increase concentration of glycosaminoglycans in posterior rabbit sclera.

PURPOSE: Glycosaminoglycans are important components of ocular tissues such as the sclera. The pressure reducing effect of a new antiglaucoma drug, latanoprost, is based on an increase in the uveo-scleral outflow by way of modulation of the intracellular matrix of the ciliary body. The purpose of the study was to test the effect of latanoprost on the content of glycosaminoglycans in rabbit cornea and sclera. METHODS: Twelve rabbits were studied. Six rabbits were treated for 12 weeks with latanoprost eye drops and 6 with hydroxypropylmethylcellulose, dextran 70 eye drops for control. Samples were taken from cornea and anterior, lateral, and posterior sclera. Glycosaminoglycans were determined quantitatively by spectrophotometry (uronic acids). RESULTS: A significant increase in the concentration of uronic acids was found in all three localisations of sclera from latanoprost-treated animals. The increase was 26%, 24%, and 20% in anterior, lateral, and posterior sclera, respectively. CONCLUSIONS: Long-term treatment with latanoprost induces biochemical changes in sclera. The results indicate that topically applied latanoprost reaches the posterior parts of the rabbit eye.

Melanoma-associated spongiform scleropathy: biochemical changes and possible relation to tumour extension.

PURPOSE: To investigate biochemical changes of the sclera in eyes with melanoma-associated spongiform scleropathy (MASS), and to analyse possible relationships between these changes and tumour extension. METHODS: Sections from 364 eyes, enucleated for choroidal and ciliary body melanoma, were examined for MASS and scleral tumour extension. Biochemical analysis was also performed on eight scleral specimens with MASS and eight specimens (controls) from morphologically normal sclera of the same eyes. The scleral thickness of each specimen was measured. Samples were delipidized, dried and weighed. The weight ratios of collagen-related amino acids were calculated based on quantitation by liquid chromatography. Amounts of glycosaminoglycans (GAGs) were determined by electrophoresis. RESULTS: Melanoma-associated spongiform scleropathy was seen in 140 eyes (38.5%). Tumour scleral extension was observed in 82 eyes. Of these 82 eyes, 75 (91.5%) had MASS (p<0.05). Biochemically, the majority of the main amino acids of the scleral collagen and total proteins were significantly lower in areas with MASS than in the control specimens. Specific GAGs and total GAGs were found in significantly higher concentrations in areas with MASS than in the control specimens. Scleral thickness was also significantly higher in areas with MASS than in the control specimens. CONCLUSIONS: The reduced content of collagen manifested by decreased amino acids and total proteins indicates collagen degradation in the vicinity of the tumour. The concomitant excessive deposition of GAGs accumulates water and may cause loosening of the already degraded collagen bundles, giving a histopathological picture of MASS. These changes could facilitate tumour cell migration and may explain the high incidence of MASS in eyes with scleral tumour extension.