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The purpose of the experimental interventional study was to examine the influence of intraocularly applied amphiregulin, a member of the epidermal growth factor (EGF) family, on axial length in young non-human primates. It included three non-human primates (Macaca mulatta), aged 4-6 years. The left eyes received three intravitreal injections of amphiregulin (400ng/50 μl) in intervals of 4 weeks, while the right eyes received three intravitreal injections of phosphate buffered solution (50 μl) at the same time points. Ocular biometry was performed in weekly intervals. At baseline, the left eyes (study eyes) were shorter than the right (control) eyes (20.69 ± 0.21 mm versus 20.79 ± 0.24 mm; P < 0.001), with an inter-eye axial length (AL) difference (left minus right eye) of -0.10 ± 0.23 mm. Inter-eye AL difference increased (P < 0.001) to 0.15 ± 0.18 mm at study end, at 12 weeks after baseline. Axial elongation during the study was higher (P < 0.001) in the left eyes (20.69 ± 0.21 mm to 21.05 ± 0.29 mm or 0.36 ± 0.30 mm) than in the right eyes (20.79 ± 0.24 mm to 20.90 ± 0.31 mm or 0.11 ± 0.17 mm). In a parallel manner, inter-eye difference in vitreous cavity depth combined with lens thickness (left eye minus right eye) increased from -0.04 ± 0.17 mm at baseline to -0.02 ± 0.21 mm (P = 0.02), 0.04 ± 0.10 mm (P = 0.002), and to 0.42 ± 0.67 mm (P < 0.001) at 5, 6, and 12 weeks after baseline, respectively. The results suggest that intravitreally applied amphiregulin as EGF family member led to an increase in axial length in adolescent non-human primates. It supports the hypothesis of amphiregulin as EGF family member being involved in the process of axial elongation., Competing Interests: Declaration of competing interest J.B. Jonas, S. Panda-Jonas: European patent EP 3 271 392, JP 2021–119 187, and US 11 008 385: "Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Patent application: European patent application: WO 2021/198 369 A1; PCT/EP2021/058 500: Agents for use in the therapeutic or prophylactic treatment of retinal pigment epithelium-associated diseases. All other authors explicitly state that they have no conflicts of interest in connection with this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To describe choroidal thickness measurements using a sequential deep learning segmentation in adults who received childhood atropine treatment for myopia control., Design: Prospective, observational study., Methods: Choroidal thickness was measured by swept-source optical coherence tomography in adults who received childhood atropine, segmented using a sequential deep learning approach., Results: Of 422 eyes, 94 (22.3 %) had no previous exposure to atropine treatment, while 328 (77.7 %) had received topical atropine during childhood. After adjusting for age, sex, and axial length, childhood atropine exposure was associated with a thicker choroid by 32.1 μm (95 % CI, 9.2-55.0; P = 0.006) in the inner inferior, 23.5 μm (95 % CI, 1.9-45.1; P = 0.03) in the outer inferior, 21.8 μm (95 % CI, 0.76-42.9; P = 0.04) in the inner nasal, and 21.8 μm (95 % CI, 2.6-41.0; P = 0.03) in the outer nasal. Multivariable analysis, adjusted for age, sex, atropine use, and axial length, showed an independent association between central subfield choroidal thickness and the incidence of tessellated fundus (P < 0.001; OR, 0.97; 95 % CI, 0.96-0.98)., Conclusions: This study demonstrated that short-term (2-4 years) atropine treatment during childhood was associated with an increase in choroidal thickness of 20-40 μm in adulthood (10-20 years later), after adjusting for age, sex, and axial length. We also observed an independent association between eyes with thicker central choroidal measurements and reduced incidence of tessellated fundus. Our study suggests that childhood exposure to atropine treatment may affect choroidal thickness in adulthood., Competing Interests: Declaration of Competing Interest Dr Jost B. Jonas has disclosed European patent EP 3 271 392, JP 2021–119187, and US 2021 0340237 A1: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia. Dr Audrey Chia has disclosed royalties from Myopine. Dr Leopold Schmetterer has disclosed consultancy fee from Thea Pharma., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To estimate the effect of atropine eyedrops at different concentrations for myopia control in children., Methods: We conducted a Bayesian random-effects network meta-analysis based on randomized controlled trials (RCT). Primary outcomes include changes in spherical equivalent error (SER) and changes in axial length (AL), mean difference (MD) together with 95% credible interval (CrI) were used to evaluate the efficacy., Results: 28 RCTs (6608 children) were included in this review. Comparing ten atropine eyedrops (0.0025%, 0.005%, 0.01%, 0.02%, 0.025%, 0.05%, 0.1%, 0.25%, 0.5% and 1% concentrations) with the placebo, the MDs and 95%CrIs of changes in SER are -0.006 (-0.269, 0.256) D, 0.216 (-0.078, 0.508) D, 0.146 (0.094, 0.199) D, 0.167 (0.039, 0.297) D, 0.201 (0.064, 0.341) D, 0.344 (0.251, 0.440) D, 0.255 (0.114, 0.396) D, 0.296 (0.140, 0.452) D, 0.331 (0.215, 0.447) D, and 0.286 (0.195, 0.337) D, respectively. The MDs and 95%CrIs of changes in AL are -0.048 (-0.182, 0.085) mm, -0.078 (-0.222, 0.066) mm, -0.095 (-0.130, -0.060) mm, -0.096 (-0.183, -0.009) mm, -0.083 (-0.164, -0.004) mm, -0.114 (-0.176, -0.056) mm, -0.134 (-0.198, -0.032) mm, -0.174 (-0.315, -0.061) mm, -0.184 (-0.291, -0.073) mm, and -0.171 (-0.203, -0.097) mm, respectively.Whether evaluated by SER or AL, 1% concentration ranks first in efficacy, but the risk of photophobia is 17 times higher than 0.01% concentration., Conclusions: 0.01% or higher concentration atropine eyedrops are effective for myopia control, while 0.0025% and 0.005% concentrations may not. As the concentration increases, the effect tends to increase, 1% concentration may have the strongest effect., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Atropine eye drops have been shown to slow the progression of myopia, but there has been limited research on the effectiveness of 0.05% atropine in treating myopia. This study aimed to investigate the safety and efficacy of 0.05% atropine eye drops in controlling myopia in children., Methods: The study included 424 participants aged 6 to 12 years between January 1, 2015, and January 1, 2021. Of these, 213 were randomly assigned to the 0.05% atropine group and 211 to the placebo group. The cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured using IOLMaster. The lens power and corneal astigmatism were also determined. The changes in ocular biometric parameters were compared between the two groups, and the contributions of ocular characteristics to SE progression were calculated and compared., Results: Over a 12-month period, the changes in spherical equivalent were -0.03 ± 0.28 and -0.32 ± 0.14 in the atropine and placebo groups, respectively ( P  = .01). The changes in axial length were 0.06 ± 0.11 and 0.17 ± 0.12, respectively ( P  = .01). At 18 and 24 months, there were significant differences in axial length and spherical equivalent between the atropine and placebo groups. Multiple regression models accounting for changes in AL, K, and lens magnification explained 87.23% and 98.32% of SE changes in the atropine and placebo groups, respectively. At 1 year ( p  = .01) and 2 years ( p  = .03), there were significant differences in photophobia between the atropine and placebo groups., Conclusions: This two-year follow-up study demonstrates that 0.05% atropine eye drops are safe and effective in preventing the development of myopia in school-aged children.

Purpose: To explore the therapeutic effects of orthokeratology lens combined with 0.01% atropine eye drops on juvenile myopia., Methods: A total of 340 patients with juvenile myopia (340 eyes) treated from 2018 to December 2020 were divided into the control group (170 cases with 170 eyes, orthokeratology lens) and observation group (170 cases with 170 eyes, orthokeratology lens combined with 0.01% atropine eye drops). The best-corrected distance visual acuity, best-corrected near visual acuity, diopter, axial length, amplitude of accommodation, bright pupil diameter, dark pupil diameter, tear-film lipid layer thickness, and tear break-up time were measured before treatment and after 1 year of treatment. The incidence of adverse reactions was observed., Results: Compared with the values before treatment, the spherical equivalent degree was significantly improved by 0.22 (0.06, 0.55) D and 0.40 (0.15, 0.72) D in the observation and control groups after the treatment, respectively (p<0.01). After the treatment, the axial length was significantly increased by (0.15 ± 0.12) mm and (0.24 ± 0.11) mm in the observation and control groups, respectively, (p<0.01). After the treatment, the amplitude of accommodation significantly declined in the observation group and was lower than that in the control group, whereas both bright and dark pupil diameters significantly increase and were larger than those in the control group (p<0.01). After the treatment, the tear-film lipid layer thickness and tear break-up time significantly declined in the two groups (p<0.01)., Conclusions: Orthokeratology lens combined with 0.01% atropine eye drops can synergistically enhance the control effect on juvenile myopia with high safety.

The aim of the study is to determine the effects of monocular 0.125% atropine daily treatment on the longer axial length (AL) eyes in children with pediatric anisometropia. This was a retrospective cohort study. The charts of children with anisometropia (aged 6-15 years) who had a > 0.2-mm difference in AL between the two eyes were reviewed. Children who received monocular treatment of 0.125% atropine in the eye with longer AL were included for final analysis. The main outcome measure was the difference in AL between the two eyes after treatment. Regression analysis was used to model the changes in AL according to the time of treatment in both eyes. Finally, forty eyes in 20 patients (mean age 10.2 years) were included in the analyses. During the treatment period, AL was controlled in the treated eyes (p = 0.389) but elongated significantly in the untreated eyes (p < 0.001). The difference in AL between the treated and untreated eyes decreased from 0.57 to 0.22 mm (p < 0.001) after the 1-year treatment period. In the regression model, the best fit for the relationship between changes in AL and time during the treatment period in the treated eyes was the quadratic regression model with a concave function. In conclusion, these data suggest that 0.125% atropine daily is an effective treatment to reduce the interocular difference of AL in eyes with axial anisometropia. This pilot study provides useful information for future prospective and larger studies of atropine for the treatment of pediatric axial anisometropia., (© 2021. The Author(s).)

Three hundred and twenty-eight myopic children, randomized to use either 0.01% (N = 166) or 0.02% (N = 162) atropine were enrolled in this study. Gender, age, body mass index(BMI), parental myopia status, atropine concentration used, pupil diameter, amplitude of accommodation, spherical equivalent refractive error (SER), anterior chamber depth (ACD) and axial length (AL) were collected at baseline and 1 year after using atropine. Rapid AL elongation was defined as > 0.36 mm growth per year. Univariate analyses showed that children with rapid AL elongation tend to be younger, have a smaller BMI, use of 0.01% atropine, narrow ACD, lower SER, shorter AL, smaller change in pupil diameter between 1 year and baseline (all P < 0.05). Multivariate logistic regression analyses confirmed that rapid AL elongation was associated with children that were younger at baseline (P < 0.0001), use of 0.01% atropine (P = 0.04), a shorter baseline AL (P = 0.03) and a smaller change in pupil diameter between 1 year and baseline (P = 0.04). Younger children with shorter AL at baseline, less change in their pupil diameter with atropine treatment and using the lower of the two atropine concentrations may undergo rapid AL elongation over a 12 months myopia control treatment period.

Oral administration of the adenosine receptor (ADOR) antagonist, 7-methylxanthine (7-MX), reduces both form-deprivation and lens-induced myopia in mammalian animal models. We investigated whether topically instilled caffeine, another non-selective ADOR antagonist, retards vision-induced axial elongation in monkeys. Beginning at 24 days of age, a 1.4% caffeine solution was instilled in both eyes of 14 rhesus monkeys twice each day until the age of 135 days. Concurrent with the caffeine regimen, the monkeys were fitted with helmets that held either -3 D (-3D/pl caffeine, n = 8) or +3 D spectacle lenses (+3D/pl caffeine, n = 6) in front of their lens-treated eyes and zero-powered lenses in front of their fellow-control eyes. Refractive errors and ocular dimensions were measured at baseline and periodically throughout the lens-rearing period. Control data were obtained from 8 vehicle-treated animals also reared with monocular -3 D spectacles (-3D/pl vehicle). In addition, historical comparison data were available for otherwise untreated lens-reared controls (-3D/pl controls, n = 20; +3D/pl controls, n = 9) and 41 normal monkeys. The vehicle controls and the untreated lens-reared controls consistently developed compensating axial anisometropias (-3D/pl vehicle = -1.44 ± 1.04 D; -3D/pl controls = -1.85 ± 1.20 D; +3D/pl controls = +1.92 ± 0.56 D). The caffeine regime did not interfere with hyperopic compensation in response to +3 D of anisometropia (+1.93 ± 0.82 D), however, it reduced the likelihood that animals would compensate for -3 D of anisometropia (+0.58 ± 1.82 D). The caffeine regimen also promoted hyperopic shifts in both the lens-treated and fellow-control eyes; 26 of the 28 caffeine-treated eyes became more hyperopic than the median normal monkey (mean (±SD) relative hyperopia = +2.27 ± 1.65 D; range = +0.31 to +6.37 D). The effects of topical caffeine on refractive development, which were qualitatively similar to those produced by oral administration of 7-MX, indicate that ADOR antagonists have potential in treatment strategies for preventing and/or reducing myopia progression., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia., (© 2020 Federation of American Societies for Experimental Biology.)

Myopic anisometropia (anisomyopia) is a specific type of refractive error that may cause fusion impairment, asthenopia, and aniseikonia. It is sometimes severe enough to reduce the quality of life. Several studies have investigated the treatment effects of orthokeratology (Ortho-K) and topical atropine on anisomyopia control. However, no study has compared these two interventions simultaneously until now. The cohort of this retrospective study included 124 children with anisomyopia who were treated with binocular Ortho-K lenses, 0.01% atropine, or 0.05% atropine. After a 2-year follow-up, the inter-eye difference in axial length (AL) significantly decreased in the Ortho-K group (P = 0.015) and remained stable in the two atropine groups. When comparing the myopia control effect, the use of Ortho-K lenses resulted in an obviously smaller change in AL than the use of 0.01% and 0.05% atropine (P < 0.01). Ortho-K treatment may reduce the degree of anisomyopia and stabilise the progression of myopia. Hence, Ortho-K might be a better choice for anisomyopic children.

The purpose of this study was to investigate the effects of latanoprost, an ocular hypotensive prostaglandin analog, on scleral collagen fibers and laminar pores in myopic guinea pigs. Young guinea pigs underwent monocular form deprivation (FD; white plastic diffusers) from 14-days of age for 10-weeks. After the first week, FD eyes also received daily topical A) latanoprost (Lat, 0.005%, n = 5) or B) artificial tears (AT; n = 5). At the end of the treatment period, animals were sacrificed, eyes enucleated and optic nerve heads (ONH) excised to include a 4 mm diameter ring of surrounding sclera for scanning electron microscopy (SEM), and an additional 6 mm ring of sclera surrounding the ONH was excised for transmission electron microscopy (TEM). For SEM, ONH samples were first immersed in 0.2M NaOH for 30 h to isolate the collagenous structures. All samples were stained with osmium tetroxide, dried through an ethanol series and finally subjected to critical point drying before imaging. Image J was used to analyze the dimensions of laminar pores (SEM images) and scleral collagen fibers (TEM images). As previously reported in a related study, latanoprost was effective in inhibiting myopia progression in FD eyes of the guinea pigs. The scleral fibers of FD myopic eyes treated with AT were smaller and more variable in cross-sectional areas compared to untreated (fellow) eyes (mean areas: 0.0059 ± 0.0013 vs. 0.0085 ± 0.002 μm 2 ; p < 0.001), consistent with scleral changes reported for human myopia. In contrast, the scleral fibers of the Lat-treated FD eyes were similar to those of fellow eyes (0.0083 ± 0.002 vs. 0.0078 ± 0.0014 μm 2 ). However, laminar pore size appeared unaffected by either the FD or drug treatments, with no significant difference found between FD eyes and their fellows, for either treatment group. That daily topical latanoprost appeared to protect against myopia-related changes in scleral collagen, rather than exaggerating them, as might be predicted from its known action on the uveoscleral extracellular matrix, lends further support its use for myopia control. In this guinea pig myopia model, the lamina cribrosa appeared unaffected., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the adjunctive effect of orthokeratology (ortho-k) and low-dose atropine eye drops on axial length elongation in fast-progressing myopic children., Methods: Axial elongation in 60 eyes of 60 subjects who completed two years of ortho-k treatment was retrospectively reviewed. They were aged between 5.6-11.6 (mean, 8.3 ± 1.5) years old when they started ortho-k treatment. During their first year of ortho-k treatment (Phase One), they all demonstrated a faster than 0.25 mm/yr axial elongation rate. They were then treated with nightly 0.01% atropine in addition to ortho-k treatment for another year (Phase Two). Annual axial elongation rates before and after atropine treatment were compared., Results: Baseline spherical equivalent refractive error was -2.65 ± 1.08 DS and axial length was 24.34 ± 0.92 mm for the study cohort. The mean axial elongation rate was 0.46 ± 0.16 mm/yr during Phase One, being significantly faster in younger children (t = -4.920, P < 0.001). When atropine was added, annual axial elongation rate significantly decreased to 0.14 ± 0.14 mm/yr (t = -11.988, P < 0.001), and those who were fast progressors in Phase One had a greater reduction in the rate of axial elongation during Phase Two (t = -8.052, P < 0.001)., Conclusions: Axial elongation rate is faster in younger children undergoing ortho-k treatment. For fast myopia progressors, low dose atropine may significantly slow axial elongation in addition to ortho-k's treatment effect. Those who have faster axial elongation after ortho-k treatment will benefit more from the addition of low dose atropine, regardless of their refractive error and age., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The putative myopia-controlling receptor is thought to be muscarinic acetylcholine receptor subtype M 4 , because mamba toxin-3 can inhibit form-deprivation myopia in chicks at a far lower concentration than atropine. However, mamba toxin-3 is equally potent at the human α 1A -, α 1D -, and α 2A -adrenoceptors. To test the hypothesis that α-adrenoceptors might be involved in regulation of eye growth, the treatment effects of α 2 -adrenoceptor agonists brimonidine, clonidine, and guanfacine, and antagonist yohimbine, on form-deprivation myopia in the chick were measured., Methods: Right eyes of White Leghorn chicks were goggled with diffusers to induce form-deprivation myopia; left eyes were left open as controls. Goggled eyes were injected intravitreally with 20 μL of vehicle, or 2, 20, or 200 nmol of brimonidine, clonidine, guanfacine, or yohimbine, 24, 72, and 120 hours after goggle application. Alternatively, myopia was inhibited physiologically by goggle removal for two hours, and the α 2 -adrenoceptor antagonist, yohimbine, was injected to test whether it could block this type of myopia inhibition. One day after the last injection, refractive error and axial length were measured., Results: Brimonidine (20 and 200 nmol) and clonidine (200 nmol) effectively inhibited experimentally induced increases in negative refractive error and axial elongation. All doses of guanfacine significantly inhibited induced negative refractive error, but only 20 and 200 nmol significantly inhibited axial elongation. Yohimbine had no effect on form-deprivation myopia, but 200 nmol reduced the myopia-inhibiting effect of goggle removal., Conclusion: High concentrations of α 2 -adrenoceptor agonists, similar to those required by atropine, inhibited chick form-deprivation myopia; antagonism by yohimbine had no effect. High-concentration yohimbine partially interfered with emmetropisation in form-deprived chicks experiencing normal vision for two hours per day. These data support the hypothesis that treatment with high concentrations of adrenergic drugs can affect experimentally induced myopia and normal visual processes., (© 2019 The Authors. Clinical and Experimental Optometry published by John Wiley & Sons Australia, Ltd on behalf of Optometry Australia.)

Purpose: To explore the effect of topical atropine on axial eye growth and emmetropization in infant marmosets., Methods: Atropine was applied to one eye from the age of 7 to 56 days in two dose regimens, High (0.1-1% twice daily, increasing with age) or moderate (Mod) (0.1% once daily). Both eyes of the marmosets were refracted, and axial dimensions were measured ultrasonically, at 14, 28, 42, 49, 56, 70, 105, 168, and 279 days of age. The time course of each measured variable was analyzed using multilevel mixed-effects modeling realized in R., Results: The logistic growth curves fitted to anterior segment depth (ASD) did not differ significantly between the dose regimens, but xmid, the age at which growth was half-maximal, and scal, the time constant of the exponential term in the logistic growth curve equation, differed significantly between the ASD of atropinized and untreated eyes (P = 0.03 and P < 0.0001, respectively), with the ASD of atropinized eyes shorter than that of untreated eyes. The splines fitted to lens thickness did not vary significantly with dose, but differed significantly (P < 0.0001) between the atropinized and untreated eyes, with the atropinized lenses thicker. Vitreous chamber depth (VCD) was not significantly different, but the variance of VCD was significantly greater (P < 0.001) in the atropinized compared with the untreated eyes. Refractive error (RE) became relatively myopic in atropinized eyes. The variance of RE in atropinized eyes was significantly greater (P < 0.0001) than in untreated eyes., Conclusions: Atropine caused the infant marmoset lens to move forward and thicken, a relative myopia, and increases in the between-animals variance in VCD, which could be considered a failure of emmetropization.

Purpose: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema., Methods: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups., Results: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123)., Conclusions: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

Purpose: To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation., Methods: The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 μg, 10 μg, 20 μg) into their right eyes, and three phosphate-buffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 μg) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem., Results: In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 μg: side difference: 0.14 ± 0.05 mm;10 μg: 0.22 ± 0.06 mm; 20 μg: 0.32 ± 0.06 mm; p < 0.001), thicker sclera (all p < 0.05) and higher cell density in the retinal nuclear layers and retinal pigment epithelium (RPE) (all p < 0.05). In animals without lens-induced myopia, the right eyes with amphiregulin antibody application (20 μg) showed reduced axial elongation (p = 0.04), and the right eyes with amphiregulin injections experienced increased (p = 0.02) axial elongation in a dose-dependent manner (1 ng: 0.04 ± 0.06 mm; 10 ng: 0.10 ± 0.05 mm; 20 ng: 0.11 ± 0.06 mm). Eyes with lens-induced axial elongation as compared to eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE., Conclusion: Amphiregulin may be associated with axial elongation in young guinea pigs., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: This study aims to assess the efficacy of the scleral collagen cross-linking method using glyceraldehyde solution for prevention of lens-induced axial elongation in New Zealand rabbits and investigate the biochemical and microstructural changes that occur., Methods: The right eyes of New Zealand rabbits aged seven weeks were randomly divided into three groups: the cross-linking group (n = 6), non-crosslinking group (n = 5), and untreated control group (n = 5). Eyes in cross-linking and non-crosslinking groups were treated with a -8.00 Diopter spherical lens over the course of two weeks. The cross-linking effects were achieved by a sub-Tenon's injection of 0.15 ml 0.5 M glyceraldehyde to eyes in the CL group. Ocular parameters were measured on the 1st, 7 th, and 14th days. Biomechanical testing, light and electronic microscopy were used., Results: Following the cross-linking treatment, eyes in the cross-linking group had a shorter axial length compared to those in the non-crosslinking group (p = 0.006). Collagen fibrils larger than 240 nm were observed in the scleral stroma of cross-linking group, which were absent in the scleral stroma of the non-crosslinking and untreated control group. The mean ultimate stress and Young's modulus was significantly greater in the cross-linking group compared to those in the non-crosslinking and untreated control group (p < 0.05). No histological damage observed in the retina or choroid., Conclusions: This study demonstrates that lens-induced axial elongation in rabbits can be effectively blocked by cross-linking using glyceraldehyde, with anatomical and mechanical modification and no deleterious effects.

The prevalence of myopia has increased worldwide in recent decades. In East Asia's metropolises ≥ 80% of young adults are affected. This dramatic increase is mainly caused by changes in lifestyle and behaviour. Atropine has been used for more than 100 years to arrest myopia progression. It has become an evidence-based treatment regimen in the last decade, although the exact mechanism of the effect of treatment is still unknown. Atropine eye drops can slow myopia progression by an average of - 0.54 dioptres (D)/year in Asian children and - 0.35 D/year in Caucasian children. However, a non-response rate of about 10% has been found. Treatment should be established in schoolchildren only (age ≥ 6 years) with myopia ≤ - 2 D (spherical equivalent, cycoplegic refraction) and with documented myopic progression of - 0.5 D in the preceding year. 0.01% eyedrops should be instilled into the lower fornix at bedtime. Atropine 0.01% therapy is well tolerated. Atropine is usually administered for 2 years since efficacy is somewhat better in the second year. During treatment, a 6-month follow-up with cycoplegic refraction and axial length measurement is recommended. After the 2-year period, atropine withdrawal is justified if progression is less than - 0.25 D/year in the second year. Even after atropine has been stopped, follow-up examinations are needed to detect any rebound. Atropine-therapy is resumed if progression is again higher than - 0.5 D/year. Topical atropine is used off-label., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

We used an ultra-long scan depth optical coherence tomography (UL-OCT) system to investigate changes in axial biometry of pseudophakic eyes during pilocarpine- induced accommodation. The right eyes from 25 healthy subjects (age range 49 to 84 years) with an intraocular lens (IOL) were imaged twice in the non-accommodative and the accommodative states. A custom-built UL-OCT instrument imaged the whole eye. Then accommodation was induced by two drops of 0.5% pilocarpine hydrochloride separated by a 5-minute interval. Following the same protocol, images were acquired again 30 minutes after the first drop. The central corneal thickness (CCT), anterior chamber depth (ACD), IOL thickness (IOLT), and vitreous length (VL) were obtained using custom automated software. The axial length (AL) was calculated by summing the CCT, ACD, IOLT, and VL. With accommodation, ACD increased by +0.08 ± 0.09 mm, while the VL decreased by -0.04 ± 0.09 mm (paired t-test each, P<0.05). CCT and IOLT remained constant during accommodation (P > 0.05). The non-accommodative AL was 23.47 ± 0.93 mm, and it increased by +0.04 ± 0.04 mm after accommodation (P<0.01). The AL increased and the IOL moved backward during pilocarpine-induced accommodation in pseudophakic eyes.

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to assess the efficacy and safety of atropine 0.5% eyedrops (ATE) for the treatment of children with low myopia (LM)., Methods: In this study, a total of 126 children with LM were randomly divided into an intervention group (administered 0.5% ATE) and a control group (administered a placebo), with 63 children in each group. The outcome measurements were changes in the spherical equivalent (SE), and axial length (AL), as well as adverse events (AEs)., Results: Compared with placebo, administration of 0.5% ATE led to less progression in LM, as measured by SE, and less increase in AL (P < .01). In addition, no serious AEs occurred in both the groups., Conclusion: About 0.5% ATE was efficacious and safe for controlling myopia in children with LM.

Purpose: Age-related changes in lens elasticity and ciliary muscle contractility can affect how ocular parameters respond to cycloplegia, and therefore intraocular lens (IOL) power measurements calculated by formulas using anterior chamber depth (ACD), lens thickness (LT), or white-to-white (WtW) for effective lens position prediction can vary. In response, using swept-source optical biometry in prepresbyopic and presbyopic eyes, we investigated changes in ocular parameters and IOL power calculations attributable to cycloplegia., Design: Cross-sectional study., Methods: In 38 prepresbyopic and 42 presbyopic eyes, we measured pupil diameter, radius of corneal curvature values, central corneal thickness, WtW, ACD, LT, and axial length both before and after cycloplegia. We determined IOL power calculations with the Sanders-Retzlaff-Kraff/theoretical, Holladay 2, and Haigis formulas. To pinpoint the effect of cycloplegia, we recorded refractive predictions in pre- and postdilation conditions according to the same IOL power calculations, even if postdilation IOL power calculations had changed., Results: With cycloplegia, pupil diameter changed significantly more in presbyopic eyes (P < .001). Central corneal thickness decreased in prepresbyopic eyes (P = .048), whereas WtW increased in presbyopic eyes (P = .02). In both groups, ACD and LT changed significantly (P < .001). IOL power calculations according to the Holladay 2 formula differed in prepresbyopic eyes (P = .042), and refractive predictions with the Holladay 2 and Haigis formulas differed significantly in prepresbyopic eyes (P = .043 and P = .022, respectively)., Conclusion: Surgeons should consider the effect of cycloplegia on refractive prediction errors and IOL power calculations determined with Haigis and Holladay 2 formulas, especially in prepresbyopic ages., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine whether pupil dilation affects biometric measurements and intraocular lens (IOL) power calculation made using the new swept-source optical coherence tomography-based optical biometer (IOLMaster 700 © ; Carl Zeiss Meditec, Jena, Germany)., Procedures: Eighty-one eyes of 81 patients evaluated for cataract surgery were prospectively examined using the IOLMaster 700 © before and after pupil dilation with tropicamide 1%. The measurements made were: axial length (AL), central corneal thickness (CCT), aqueous chamber depth (ACD), lens thickness (LT), mean keratometry (MK), white-to-white distance (WTW) and pupil diameter (PD). Holladay II and SRK/T formulas were used to calculate IOL power. Agreement between measurement modes (with and without dilation) was assessed through intraclass correlation coefficients (ICC) and Bland-Altman plots., Results: Mean patient age was 75.17±7.54 years (range: 57-92). Of the variables determined, CCT, ACD, LT and WTW varied significantly according to pupil dilation. Excellent intraobserver correlation was observed between measurements made before and after pupil dilation. Mean IOL power calculation using the Holladay 2 and SRK/T formulas were unmodified by pupil dilation., Conclusions: The use of pupil dilation produces statistical yet not clinically significant differences in some IOLMaster 700 © measurements. However, it does not affect mean IOL power calculation., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

This study analyzed the luminance and color emmetropization response in chicks treated with the nonselective parasympathetic antagonist atropine and the sympathetic β-receptor blocker timolol. Chicks were binocularly exposed (8h/day) for 4days to one of three illumination conditions: 2Hz sinusoidal luminance flicker, 2Hz sinusoidal blue/yellow color flicker, or steady light (mean 680lux). Atropine experiments involved monocular daily injections of either 20μl of atropine (18nmol) or 20μl of phosphate-buffered saline. Timolol experiments involved monocular daily applications of 2 drops of 0.5% timolol or 2 drops of distilled H2O. Changes in the experimental eye were compared with those in the fellow eye after correction for the effects of saline/water treatments. Atropine caused a reduction in axial length with both luminance flicker (-0.078±0.021mm) and color flicker (-0.054±0.017mm), and a reduction in vitreous chamber depth with luminance flicker (-0.095±0.023mm), evoking a hyperopic shift in refraction (3.40±1.77D). Timolol produced an increase in axial length with luminance flicker (0.045±0.030mm) and a myopic shift in refraction (-4.07±0.92D), while color flicker caused a significant decrease in axial length (-0.046±0.017mm) that was associated with choroidal thinning (-0.046±0.015mm). The opposing effects on growth and refraction seen with atropine and timolol suggest a balancing mechanism between the parasympathetic and β-receptor mediated sympathetic system through stimulation of the retina with luminance and color contrast., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal abnormalities. In addition, pathological myopia is a common irreversible cause of visual impairment and blindness. Our study demonstrates the effect of scleral crosslinking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. The axial length of the eyeball was measured by A-scan ultrasound in New Zealand white rabbits aged 13 days (male and female). The eye then underwent 360° conjunctival peritomy with scleral crosslinking, followed by tarsorrhaphy. Axial elongation was induced in 13 day-old New Zealand rabbits by suturing their right eye eyelids (tarsorrhaphy). The eyes were divided into quadrants, and every quadrant had two scleral irradiation zones, each with an area of 0.2 cm² and a radius of 4 mm. Crosslinking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones 20 sec before ultraviolet-A irradiation and every 20 sec during the 200 sec irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm² (total UVA light dose, 57 J/cm²). Tarsorrhaphies were removed on day 55, followed by repeated axial length measurements. This study demonstrates that scleral crosslinking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model.

lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 ± 0.08 D/day) was significantly less than in the FD group (-0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 ± 0.05 D/day) and H2O + ascorbic acid (-0.08 ± 0.05 D/day) both almost completely blocked myopia development. The treated eye vitreous chamber elongation, compared with the control eye, in all groups was consistent with the amount of myopia. When FD continued (days 12-16) without injections in the water and water + ascorbic acid groups, the rate of myopia development quickly increased. Thus, it appears the vehicles affected retinal signaling rather than causing damage. The effect of water and water + ascorbic acid may be due to reduced osmolality or ionic concentration near the tip of the injection pipette. The effect of ascorbic acid, compared to NaCl alone, may be due to its reported dopaminergic activity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The purpose of this study was to investigate the effects of pupil dilation on the parameters of the AL-Scan (Nidek Co., Ltd, Gamagori, Japan). We compared the measurements of axial length (AL), anterior chamber depth (ACD), central corneal keratometry reading, pupil diameter, and intraocular lens (IOL) power of 72 eyes of 72 healthy volunteers and patients scheduled for cataract surgery before and 45 min after instillation of cyclopentolate hydrochloride 1 % using the AL-Scan. Intraobserver repeatability was assessed by taking three consecutive recordings of ACD and AL. Only ACD readings were significantly different between predilation and postdilation (P < 0.001). The difference of the other measurements between two sessions was not statistically significant (P > 0.001). Only two cases in the study demonstrated changes in IOL power higher than 0.5 D. The intraobserver repeatability of both devices was good (CV values for ACD and AL were 0.16 and 0.20 %, respectively). Dilated pupil size did not affect the measurement of IOL power using the A-Scan optical biometer, but increase in ACD after dilation should be taken into account when performing refractive surgeries in which ACD is very important such as phakic anterior chamber IOL implantation.

Purpose: To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years., Design: Randomized, double-masked clinical trial., Participants: A total of 400 children originally randomized to receive atropine 0.5%, 0.1%, or 0.01% once daily in both eyes in a 2:2:1 ratio., Methods: Children received atropine for 24 months (phase 1), after which medication was stopped for 12 months (phase 2). Children who had myopia progression (≥-0.50 diopters [D] in at least 1 eye) during phase 2 were restarted on atropine 0.01% for a further 24 months (phase 3)., Main Outcome Measures: Change in spherical equivalent and axial length over 5 years., Results: There was a dose-related response in phase 1 with a greater effect in higher doses, but an inverse dose-related increase in myopia during phase 2 (washout), resulting in atropine 0.01% being most effective in reducing myopia progression at 3 years. Some 24%, 59%, and 68% of children originally in the atropine 0.01%, 0.1%, and 0.5% groups, respectively, who progressed in phase 2 were restarted on atropine 0.01%. Younger children and those with greater myopic progression in year 1 were more likely to require re-treatment. The lower myopia progression in the 0.01% group persisted during phase 3, with overall myopia progression and change in axial elongation at the end of 5 years being lowest in this group (-1.38±0.98 D; 0.75±0.48 mm) compared with the 0.1% (-1.83±1.16 D, P = 0.003; 0.85±0.53 mm, P = 0.144) and 0.5% (-1.98±1.10 D, P < 0.001; 0.87±0.49 mm, P = 0.075) groups. Atropine 0.01% also caused minimal pupil dilation (0.8 mm), minimal loss of accommodation (2-3 D), and no near visual loss compared with higher doses., Conclusions: Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with less visual side effects compared with higher doses of atropine., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Scleral cross-linking (SXL) by riboflavin and light application has been introduced as a possible treatment to increase scleral tissue stiffness and to inhibit excessive axial elongation of highly myopic eyes. We evaluated an ocular tissue damage threshold for blue light irradiation, and used SXL treatment to induce eye growth inhibition., Methods: The sclera of 3-week-old rabbits (39 pigmented and 15 albino rabbits) were treated with different blue light intensities (450 ± 50 nm) and riboflavin. Alterations and a damage threshold were detected in ocular tissues by means of light microscopy and immunohistochemistry. The influence of SXL on the eye growth was examined in 21 young rabbits and was measured by using A-scan ultrasonography, micrometer caliper, and for selected eyes additionally by MR imaging., Results: Light microscopic examinations demonstrated degenerative changes in ocular tissue after irradiation with blue light intensities above 400 mW/cm(2) (with and without riboflavin application). Therefore, that light intensity was defined as the damage threshold. Tissue alteration in retina, choroid, and sclera and activation of retinal microglia cells and Müller cells could be earlier observed at blue light intensities of 150 and 200 mW/cm(2). Albino rabbits were less sensitive to this SXL treatment. A significant reduction of the eye growth could be detected by SXL treatment with the minimal efficient blue light intensity of 15 mW/cm(2) and maintained stable for 24 weeks., Conclusions: SXL with riboflavin and blue light intensities below a defined damage threshold can induce a long lasting growth inhibitory effect on young rabbit eyes. Therefore, SXL might be a realistic approach to inhibit eye elongation in highly myopic eyes.

Purpose: To evaluate the efficacy of topical atropine 1% in promoting unaided visual acuity, reducing myopia, and slowing the progression of ocular axial elongation in Chinese children with low myopia., Methods: Children with low myopia were randomly assigned to one of two groups, receiving either atropine 1% (treatment group) or placebo eyedrops (control group) once nightly for 1 year. After instillation of 3 drops of cyclopentolate 1%, unaided visual acuity, cycloplegic refraction, and ocular axial length were tested and recorded at baseline (2 weeks after atropine or vehicle eyedrops), 3 months, 6 months, 9 months, and 1 year., Results: A total of 132 children 7-12 years of age with a refractive error of spherical equivalent -0.50 D to -2.00 were included. After 1 year, the mean unaided visual acuity in the treatment group was 0.31 ± 0.16 logMAR; in the control group, 0.66 ± 0.15 logMAR, (P < 0.0001). After treatment for 1 year, there was a decrease of 0.32 ± 0.22 D from baseline in the treatment group and an increase of -0.85 ± 0.31 D in the control group (P < 0.0001). The axial elongation in the treatment group was -0.03 ± 0.07 mm; in the control group, 0.32 ± 0.15 mm (P < 0.0001)., Conclusions: In this study cohort, topical atropine1% reduced the degree of low myopia and slowed the progression of ocular axial elongation in children., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

The aim was to investigate the effects of the GABAB receptor antagonist, CGP46381, on form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25). The deprived eyes were treated with daily subconjunctival injections (100 μl) of either 2% CGP46381, 0.2% CGP46381, or saline or received no injection. The fellow eyes were left untreated. Another six animals received no treatment. At the start and end of the treatment period, ocular refractions were measured using retinoscopy and vitreous chamber depth (VCD) and axial length (AL) using A-scan ultrasound. All of the deprived eyes developed relative myopia (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001). The highest dose tested, 2% CGP46381, significantly inhibited myopia development compared to saline (2% CGP46381: -1.08 ± 0.40 D, saline: -4.33 ± 0.67 D, P < 0.01). The majority of these effects were due to less AL (2% CGP46381: 0.03 ± 0.01 mm, saline: 0.13 ± 0.02 mm, P < 0.01) and VCD (2% CGP46381: 0.02 ± 0.01 mm, saline: 0.08 ± 0.01 mm, P < 0.01) elongation. The lower dose tested, 0.2% CGP46381, did not significantly inhibit FDM (P > 0.05). Subconjunctival injections of CGP46381 inhibit FDM development in guinea pigs in a dose-dependent manner.

Purpose: To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs., Methods: A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed., Results: Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = -4.38 ± 0.57D, 0.3 % TPMPA = -3.00 ± 0.48D, P < 0.01; 1 % TPMPA = -0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05)., Conclusions: Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the effects of topical cyclopentolate on ocular biometry parameters in healthy young adults., Methods: Ocular biometry measurements were performed twice with 45-minute intervals by use of the IOLMaster. Effects of topical application of 1% cyclopentolate were examined in 25 eyes from 25 young adults (group 1) before and after its application. As a control (cyclopentolate-free, group 2), 30 eyes from 30 age- and sex-matched healthy subjects were evaluated within the same period., Results: There was no difference between the groups with respect to mean (±SD) ages (group 1: 23 [±3.19] years [range, 18 to 28 years] vs. group 2: 22.6 [±2.7] years [range, 18 to 28 years], p = 0.616). In group 1, the anterior chamber depth and horizontal iris width (white-to-white distance) measurements between the two sessions were significantly different, whereas the axial length was not. In group 2, none of these parameters were different between the two sessions., Conclusions: Topical application of 1% cyclopentolate caused an increase in the anterior chamber depth and white-to-white distance values without any significant effect on axial length measurement. It is necessary to consider these effects on measurements taken with an IOLMaster in young adults in whom 1% cyclopentolate has been applied.

Our study demonstrates the effect of scleral cross-linking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. Axial length of the eyeball was measured by A-scan ultrasound in 22 New Zealand white rabbits aged 13 days. The right eyes then underwent 360-degree conjunctival peritomy with (experimental group, n = 11) or without (control group, n = 11) scleral cross-linking, followed by tarsorrhaphy. The left eyes served as a control eye. In the experimental group, the right eyeballs were divided into quadrants, and every quadrant had either 2 (n = 8) or 6 (n = 3) scleral irradiation zones, each with an area of 0.2 cm² and radius of 4 mm. Cross-linking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones at 20 s before ultraviolet-A irradiation and every 20 s during the 200-s irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm² (total UVA light dose, 57 J/cm²). Tarsorrhaphies were removed on day 55, followed by repeated axial-length measurement. In the control group, mean axial length in the right eyes increased from 10.50 ± 0.67 mm at baseline to 15.69 ± 0.39 mm 55 days later, for a mean change of 5.19 ± 0.85 mm. In the experimental group, corresponding values were 10.68 ± 0.74 mm and 14.29 ± 0.3 mm, for a mean change of 3.61 ± 0.76 mm. The between-group difference in the change in mean axial length was statistically significant (p < 0.001, Mann-Whitney nonparametric test). The present manuscript demonstrates that scleral cross-linking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The canonical Wnt signaling pathway plays important roles in cellular proliferation and differentiation, axonal outgrowth, cellular maintenance in retinas. Here we test the hypothesis that elements of the Wnt signaling pathway are involved in the regulation of eye growth and prevention of myopia, in the mouse form-deprivation myopia model., Methodology/principal Findings: (1) One hundred twenty-five C57BL/6 mice were randomly distributed into form-deprivation myopia and control groups. Form-deprivation myopia (FDM) was induced by suturing the right eyelid, while the control group received no treatment. After 1, 2, and 4 weeks of treatment, eyes were assessed in vivo by cycloplegic retinoscopic refraction and axial length measurement by photography or A-scan ultrasonography. Levels of retinal Wnt2b, Fzd5 and β-catenin mRNA and protein were evaluated using RT-PCR and western blotting, respectively. (2) Another 96 mice were divided into three groups: control, drugs-only, and drugs+FDM (by diffuser). Experimentally treated eyes in the last two groups received intravitreal injections of vehicle or the proteins, DKK-1 (Wnt-pathway antagonist) or Norrin (Wnt-pathway agonist), once every three days, for 4 injections total. Axial length and retinoscopic refraction were measured on the 14th day of form deprivation. Following form-deprivation for 1, 2, and 4 weeks, FDM eyes had a relatively myopic refractive error, compared with contralateral eyes. There were no significant differences in refractive error between right and left eye in control group. The amounts of Wnt2b, Fzd5 and β-catenin mRNA and protein were significantly greater in form-deprived myopia eyes than in control eyes.DKK-1 (antagonist) reduced the myopic shift in refractive error and increase in axial elongation, whereas Norrin had the opposite effect in FDM eyes., Conclusions/significance: Our studies provide the first evidence that the Wnt2b signaling pathway may play a role in the development and progression of form-deprivation myopia, in a mammalian model.

Myopia is the most frequent cause of distance impairment in the world and is creating an alarming global epidemic with deleterious ramifications for the quality of life and economic health of individuals and nations as a whole. In addition to being immediately disadvantageous, myopia increases the risk of serious disorders such as myopic macular degeneration, retinal detachment, glaucoma, and cataract and is a leading cause of visual impairment and blindness across many countries. The reduction in age of onset of myopia is of great concern since the earlier the onset, the more myopic the individual will become, with all the attendant increased risks of accompanying debilitating eye conditions. The economic burden is great; both in consequences of uncorrected refractive error and also in the provision of devices for correcting visual acuity. Earlier onset of myopia increases the lifetime economic burden related to loss of productivity and independence, leading to a reduced quality of life. Recent data suggest addressing accommodation per se has little direct amelioration of myopia progression. Pharmacological interventions that effect changes in the sclera show promising efficacy, whereas optical interventions based on a myopic shift in the retinal image are proving to effect up to 55% reduction in the rate of progression of myopia. Early contact lens and spectacle interventions that reduce the rate of progression of myopia are able to significantly reduce the burden of myopia. These non-pharmacological interventions show profound promise in reducing the overall associated morbidity of myopia.

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the immediate and short-term effects of intravitreal injection of 1.25 mg/0.05 ml of bevacizumab on intraocular pressure related to different ocular axial lengths., Design: A prospective case series of consecutive patients referred to the Department of Ophthalmology, San Pietro-Fatebenefratelli Hospital, from September 2011 through January 2011., Methods: Twenty-five patients (10 men and 15 women, mean age 70.2 ± 8.98 years) scheduled for intravitreal injection of bevacizumab for the treatment of neovascular age-related macular degeneration were enrolled in this study. Axial length was measured preoperatively using IOLMaster. Intraocular pressure was measured before injection, after 1 min and after 15 min using Tono-Pen XL tonometry., Results: The mean intraocular pressure change following the intravitreal bevacizumab injection was 21.92 ± 6.95 mmHg after 1 min and 6.24 ± 3.77 mmHg after 15 min. The mean axial length of the examined eyes was 23.2 ± 1.06 mm. A good correlation was observed between the axial length and intraocular pressure rise after both 1 (R (2) = 0.752, p < 0.001) and 15 min (R (2) = 0.559, p < 0.001)., Conclusions: Patients undergoing intravitreal injection of 0.05 ml of bevacizumab can be exposed to intraocular pressure increases correlated to ocular axial length.

Purpose: To study susceptibility to glaucoma injury as it may be affected by mutations in ocular connective tissue components., Methods: Mice homozygous for an N-ethyl-N-nitrosourea induced G257D exchange (Gly to Asp) missense mutation (Aca23) in their collagen 8A2 gene were studied to measure intraocular pressure (IOP), axial length and width, number of retinal ganglion cells (RGC), and inflation responses. Three month old homozygous Aca23 mutant and wild type (WT) mice had 6 weeks exposure to elevated IOP induced by polystyrene microbead injection. Additional Aca23 and matched controls were studied at ages of 10 and 18 months., Results: Aca23 mice had no significant difference from WT in IOP level, and in both strains IOP rose with age. In multivariable models, axial length and width were significantly larger in Aca23 than WT, became larger with age, and were larger after exposure to glaucoma (n=227 mice). From inflation test data, the estimates of scleral stress resultants in Aca23 mice were similar to age-matched and younger WT C57BL/6 (B6) mice, while the strain estimates for Aca23 were significantly less than those for either WT group in the mid-sclera and in some of the more anterior scleral measures (p<0.001; n=29, 22, 20 eyes in Aca23, older WT, younger WT, respectively). With chronic IOP elevation, Aca23 eyes increased 9% in length and 7% in width, compared to untreated fellow eyes (p<0.05, <0.01). With similar elevated IOP exposure, WT eyes enlarged proportionately twice as much as Aca23, increasing in length by 18% and in nasal-temporal width by 13% (both p<0.001, Mann-Whitney test). In 4 month old control optic nerves, mean RGC axon number was not different in Aca23 and WT (46,905±7,592, 43,628±11,162, respectively; p=0.43, Mann-Whitney test, n=37 and 29). With chronic glaucoma, Aca23 mice had a mean axon loss of only 0.57±17%, while WT mice lost 21±31% (median loss: 1% versus 10%, n=37, 29, respectively; p=0.001; multivariable model adjusting for positive integral IOP exposure)., Conclusions: The Aca23 mutation in collagen 8α2 is the first gene defect found to alter susceptibility to experimental glaucoma, reducing RGC loss possibly due to differences in mechanical behavior of the sclera. Detailed study of the specific changes in scleral connective tissue composition and responses to chronic IOP elevation in this strain could produce new therapeutic targets for RGC neuroprotection.

Choroidal neovascularisation secondary to pathological myopia is the most common cause of severe visual impairment in myopic patients younger than 50 years old. The typical features of myopic CNV in contrast to age-related macular degeneration as well as the anatomic characteristics have an impact on the parameters of the baseline and follow-up examinations. As the usually small fibrovascular lesions show a rapid progression in the spontaneous course of the disease and lead to irreversible damage to the photoreceptors, prompt initiation of treatment is mandatory. The superior functional results of anti-VEGF drugs provide the reason for the first-line status of this treatment modality. Increasing safety data and consistent results of prospective pilot trials have proved photodynamic therapy to be inferior. There are signs that PRN-based treatment algorithms may allow for less frequent dosing than in other retinal diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (© 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.)

Aim: To evaluate the effects of orally administered black-currant (BC) extract on the enlargement of globe component dimensions induced in chicks by wearing negative lenses., Methods: Negative lenses (-8 D) were worn on the right eyes by 8-day-old chicks, and their fellow eyes acted as controls. BC extract and distilled water (vehicle control) were orally administered once a day for 3 days. To confirm the effect of BC anthocyanins (BCAs), they were intravenously administered once a day for 3 days. Dimensions of globe components of right eyes and fellow eyes were measured with an A-scan ultrasound instrument on the third day (day 4) after placement of the negative lenses., Results: Orally administered BC extract significantly inhibited enlargement of vitreous-chamber depth, axial and ocular lengths in a dose-dependent manner when compared to controls. Intravenously administered BCAs also inhibited elongation of vitreous-chamber depth and axial length when compared to controls., Conclusions: This is the first evidence that BC extract and BCAs could inhibit enlargement of globe component dimensions in a negative lens-induced chick myopia model., (Copyright © 2010 S. Karger AG, Basel.)