The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia.

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

Differential Impact of 0.01% and 0.05% Atropine Eyedrops on Ocular Surface in Young Adults.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults. Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained. Results: The mean OSI peaked after two days of administration of 0.05% atropine (ß = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (ß = -7.73, P < 0.001) and NIKBUT-average (ß = -8.10, P < 0.001); the OSDI peaked after 14 days (ß = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: ß = -4.46, P = 0.005; NIKBUT-average: ß = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped. Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect. Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

Acute Myopic Shift after a Single Dose of Acetazolamide: A Case Report and Review of the Literature.

We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg acetazolamide. The drug was discontinued and following cycloplegia and topical steroid therapy, we observed progressive deepening of the anterior chamber, reopening of the iridocorneal angle, and complete resolution of the myopic shift after 5 days. A literature review since 1956 identified 23 cases, including ours, which developed a myopic shift after a median time of 24 h (3 - 24) following a median dose of 500 mg (125 - 1000) acetazolamide, with about a third complicated by angle closure ocular hypertension. This presumed idiosyncratic reaction can occur without prior drug exposure and independent of the phakic status. Treatment options include systematic drug withdrawal associated with cycloplegia, anti-glaucomatous agents, and/or corticosteroids. Full recovery is achieved within about 5 days (2 - 14). Given the widespread use of acetazolamide, awareness of this idiosyncratic reaction is crucial to avoid complications of acute angle-closure glaucoma.

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application.

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Impact of Various Concentrations of Low-Dose Atropine on Pupillary Diameter and Accommodative Amplitude in Children with Myopia.

Purpose: To assess over 2 weeks, the effect of 3 different low concentrations of atropine on pupillary diameter and accommodative amplitude in children with myopia. Methods: Fifty-eight children with myopia [spherical equivalent (SE) of -0.50 diopters (D) or worse, astigmatism of less than or equal to 2.00 D] were randomly allocated to 3 groups receiving 0.01%, 0.02%, or 0.03% atropine eye drops, once nightly for 2 weeks. The primary outcome was the change from baseline in pupillary diameter and accommodative amplitude with each of the concentrations. Results: Fifty-seven participants (114 eyes), aged between 6 and 12 years, completed the 2-week trial (mean age 9.3 ± 1.7 years and mean SE -3.53 ± 1.79 D). After 2 weeks of use, all the 3 concentrations were found to have a statistically significant effect on both the pupillary diameter and accommodative amplitude. Accommodative amplitude reduced by an average of 5.23 D, 9.28 D, and 9.32 D, and photopic pupil size increased by an average of 0.95 ± 1.05 mm, 1.65 ± 0.93 mm, and 2.16 ± 0.88 mm with 0.01%, 0.02%, and 0.03%, respectively. Of the eyes, a total of 5.3% and 5.9% of the eyes on 0.02% and 0.03% atropine had a mean residual accommodative amplitude of <5 D. The percentage of eyes having a pupillary dilation >3 mm were 4.8%, 10.5%, and 23.5% for 0.01%, 0.02%, and 0.03% atropine, respectively. Conclusions: Low-dose atropine had an effect on pupillary diameter and accommodative amplitude. With the highest concentration assessed, that is, 0.03% nearly 1 of 4 eyes had pupillary dilation of >3 mm. Clinical Trial Registration number: NCT03699423.

Comparison of the long-term effects of atropine in combination with Orthokeratology and defocus incorporated multiple segment lenses for myopia control in Chinese children and adolescents.

PURPOSE: The aim of this study was to evaluate the efficacy of Orthokeratology (Ortho-K), defocus incorporated multiple segment (DIMS) lens, combined Ortho-K/atropine, and combined DIMS/atropine for myopia control in children. METHODS: A retrospective study included 167 myopic children aged 6-14 years with a spherical equivalent refraction (SER) of -0.75 to -4.00 diopter treated with Ortho-K (OK, n = 41), combined Ortho-K/atropine (OKA, n = 43), DIMS (n = 41), or combined DIMS/atropine (DIMSA, n = 42). Axial length (AL) was measured at baseline and at 3, 6, 9 and 12 months. Axial elongation over time and between groups were analysed. RESULTS: After 12 months, the AL change was 0.20 ± 0.12 mm, 0.12 ± 0.14 mm, 0.22 ± 0.14 mm, and 0.15 ± 0.15 mm in the OK, OKA, DIMS, and DIMSA, respectively. There was no significant difference in AL change between OK and DIMS. OKA and DIMSA significantly slowed axial elongation compared to OK and DIMS monotherapy. After stratification by age, in the subgroup aged 6-10 years, there was significant difference in AL change between OKA and DIMS (p = 0.013), and no difference between other groups, while in the subgroup aged 10-14 years, the difference between OKA and DIMS became insignificant (p = 0.237), and the difference between OK and OKA, OK and DIMSA, DIMS and DIMSA became significant. CONCLUSIONS: Ortho-K and DIMS lenses show similar reductions in myopia progression among children with low initial myopia. Atropine can significantly improve the efficacy of myopia control of both Ortho-K and DIMS lenses, and this add-on effect is better in older children.

3D printed fibroblast-loaded hydrogel for scleral remodeling to prevent the progression of myopia.

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

Low-dose atropine 0.01% for the treatment of childhood myopia: a pan-India multicentric retrospective study.

OBJECTIVE: The objective of this study was to assess the efficacy of low-dose atropine 0.01% in controlling myopia progression among Indian children over a 2-year period. METHODS: This retrospective study, conducted across 20 centres in India, monitored the progression of myopia over 2 years after initiating treatment with 0.01% atropine eye drops. This included children between 6 and 14 years with baseline myopia ranging from -0.5 D to -6 D, astigmatism≤-1.5 D, anisometropia ≤ -1 D and documented myopia progression of ≥0.5 D in the year prior to starting atropine. Subjects with any other ocular pathologies were excluded. RESULTS: A total of 732 children were included in the data analysis. The mean age of the subjects was 9.3±2.7 years. The mean myopia progression at baseline (1 year before starting atropine) was -0.75±0.31 D. The rate of myopia progression was higher in younger subjects and those with higher baseline myopic error. After initiating atropine, myopia progression significantly decreased to -0.27±0.14 D at the end of the first year and -0.24±0.15 D at the end of the second year (p<0.001). Younger children (p<0.001) and higher baseline myopia (p<0.001) was associated with greater myopia progression and poor treatment response (p<0.001 for both). CONCLUSION: Low-dose atropine (0.01%) effectively reduces myopia progression over 2 years in Indian children.

Low concentration atropine and myopia: a narrative review of the evidence for United Kingdom based practitioners.

The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.

Effects on radius of curvature and refractive power of the cornea and crystalline lens by atropine 0.01% eye drops.

PURPOSE: The morphological changes in the cornea and crystalline lens have not been closely evaluated after the administration of atropine 0.01%. This study aims to evaluate the radii of curvature and refractive power of the cornea and lens in myopic eyes during atropine 0.01% treatment. METHODS: Children aged 6-14 years with myopia <-6.0 D were randomized to receive atropine 0.01% once nightly with single vision lenses or simply wear single vision lenses. Ocular biometric parameters were measured using the IOLMaster 700 biometry and the radii of corneal and lenticular curvature were simulated using a customized program. RESULTS: At the 9-month visit, 69 atropine-treated eyes and 50 control eyes were included in the final analyses. In atropine-treated eyes, the posterior corneal surface steepened (-0.05 ± 0.13 mm) and the anterior lenticular surface flattened (0.20 ± 0.69 mm) significantly within 3-6 months, whereas the posterior corneal surface and anterior lenticular surface gradually flattened (0.07 ± 0.23 and 0.32 ± 0.80 mm respectively) in the control eyes over 9 months. The difference in the change of corneal refractive power was significant between groups (-0.03 ± 0.18 D vs. 0.11 ± 0.24 D, p = 0.001), while that in the change of lenticular refractive power was statistically insignificant (0.01 ± 0.92 D vs. -0.22 ± 0.86 D, p = 0.161). CONCLUSIONS: The administration of atropine 0.01% exhibited a clinically short and subtle impact on the cornea and lens, which may shed light on new targets of action for atropine in inhibiting myopia.

Optical interventions for myopia control.

A range of optical interventions have been developed to slow the progression of myopia. This review summarizes key studies and their outcomes. Peer-reviewed, randomized controlled clinical trials of at least 18 months duration were identified. Randomized clinical trials were identified and summarised: 13 for spectacles, 5 for overnight orthokeratology, 5 for soft contact lenses, and 3 for orthokeratology combined with low concentration atropine. Overnight orthokeratology trials were the most consistent with 2-year slowing of axial elongation between 0.24 and 0.32 mm. Other modalities were more variable due to the wide range of optical designs. Among spectacle interventions, progressive addition lenses were the least effective, slowing axial elongation and myopia progression by no more than 0.11 mm and 0.31 D, respectively. In contrast, novel designs with peripheral lenslets slow 2-year elongation and progression by up to 0.35 mm and 0.80 D. Among soft contact lens interventions, medium add concentric bifocals slow 3-year elongation and progression by only 0.07 mm and 0.16 D, while a dual-focus design slows 3-year elongation and progression by 0.28 mm and 0.67 D. In summary, all three optical interventions have the potential to significantly slow myopia progression. Quality of vision is largely unaffected, and safety is satisfactory. Areas of uncertainty include the potential for post-treatment acceleration of progression and the benefit of adding atropine to optical interventions.

Myopia outcome study of atropine in children: Two-year result of daily 0.01% atropine in a European population.

PURPOSE: The Myopia Outcome Study of Atropine in Children (MOSAIC) is an investigator-led, double-masked, randomized controlled trial investigating the efficacy and safety of 0.01% atropine eye drops for managing myopia progression in a predominantly White, European population. METHODS: Children aged 6-16 years with myopia were randomly allocated 2:1 to nightly 0.01% atropine or placebo eye drops in both eyes for 2 years. The primary outcome was cycloplegic spherical equivalent (SE) progression at 24 months. Secondary outcomes included axial length (AL) change, safety and acceptability. Linear mixed models with random intercepts were used for statistical analyses. RESULTS: Of 250 participants enrolled, 204 (81.6%) completed the 24-month visit (136 (81.4%) treatment, 68 (81.9%) placebo). Baseline characteristics, drop-out and adverse event rates were similar between treatment and control groups. At 24 months, SE change was not significantly different between 0.01% atropine and placebo groups (effect = 0.10 D, p = 0.07), but AL growth was lower in the 0.01% atropine group, compared to the placebo group (-0.07 mm, p = 0.007). Significant treatment effects on SE (0.14 D, p = 0.049) and AL (-0.11 mm, p = 0.002) were observed in children of White, but not non-White (SE = 0.05 D, p = 0.89; AL = 0.008 mm, p = 0.93), ethnicity at 24 months. A larger treatment effect was observed in subjects least affected by COVID-19 restrictions (SE difference = 0.37 D, p = 0.005; AL difference = -0.17 mm, p = 0.001). CONCLUSIONS: Atropine 0.01% was safe, well-tolerated and effective in slowing axial elongation in this European population. Treatment efficacy varied by ethnicity and eye colour, and potentially by degree of COVID-19 public health restriction exposure during trial participation.

Short-term effects of cyclopentolate and tropicamide eye drops on macular choroidal thickness in myopic children.

BACKGROUND: To investigate the short-term effects of cyclopentolate and tropicamide eyedrops on choroidal thickness (ChT) in myopic children using placebo or low-dose atropine eyedrops. METHODS: The analysis included 242 myopic individuals (7-19 years) enrolled in two randomised placebo-controlled clinical trials of low-dose atropine eyedrops. Cycloplegia was induced using either one drop of 1% cyclopentolate (n = 161), two drops of 1% cyclopentolate (n = 32) or two drops of 1% tropicamide (n = 49). ChT measurements were taken using swept-source optical coherence tomography before and 30 min after administering the cycloplegic eye drops. A subset of 51 participants underwent test-retest measurements prior to cycloplegia. RESULTS: Mean changes in subfoveal ChT after two drops of tropicamide and one and two drops of cyclopentolate were -2.5 µm (p = 0.10), -4.3 µm (p < 0.001) and -9.6 µm (p < 0.001), respectively. Subfoveal ChT changes after one and two drops of cyclopentolate were significantly greater than the test-retest changes (test-retest mean change: -3.1 µm; p < 0.05), while the tropicamide group was not significantly different (p = 0.64). Choroidal thinning post-cyclopentolate was not significantly different between atropine and placebo treatment groups (p > 0.05 for all macular locations). The coefficient of repeatability (CoR) in the tropicamide group (range: 8.2-14.4 µm) was similar to test-retest (range: 7.5-12.2 µm), whereas greater CoR values were observed in the cyclopentolate groups (one drop: range: 10.8-15.3 µm; two drops: range: 12.2-24.6 µm). CONCLUSIONS: Cyclopentolate eye drops caused dose-dependent choroidal thinning and increased variation in pre- to post-cycloplegia measurements compared with test-retest variability, whereas tropicamide did not. These findings have practical implications for ChT measurements when cyclopentolate is used, particularly for successive measurements.

Preservatives and pH in low-dose atropine formulations for clinical trials.

Over a century ago, atropine has been tested to arrest myopia progression with good results. In recent years, many randomized clinical trials have tested different concentrations against placebo. Three recent such studies with low-dose atropine showed that it was less effective than previous studies, even the last one showing no difference in myopia progression between the treated and control group. Previous randomized studies had been performed in Asian populations, and these last three were extended to Western Caucasian populations, based on the initial observation that differences in iris pigmentation could be a factor for a difference in effectiveness. We have noticed that the three last studies in the West have used the same patented formulation, while previous studies have preferred compounded low-dose atropine. Here we review how the power of hydrogen (pH) and preservatives could account for differences in drug penetration to the eye, possibly explaining the differences between studies.