Search Results (19)

Using micro-structure components in spectacle lenses has enabled myopia progression control in children and teenagers. However, the optical design of these spectacle lenses has never been discussed, leading to a lack of correct understanding of the underlying optical treatment principles. In this work, array-patterned hexagonal lenslets with two powers of opposite signs were proposed to construct a lenslet array-integrated (LARI) spectacle lens developed for an ongoing, randomized, controlled clinical trial and to support the optical approach to myopia control leveraging retinal image blur. We found that the phase modulation induced by the micro-structures of the lenslet array contributes to the increase in RMS wavefront aberrations, leading to image blur, further inspiring the novel array-patterned micro-structure design with high-order phase elements (HOPEs). The optical performance of both LARI and HOPE spectacle lenses was investigated by simulation and experiment. Full article

Background: Cycloplegic refraction is crucial in pediatric eye assessments. While spherical refraction changes due to cycloplegia are well-documented, astigmatic alterations remain unclear. This study assessed the agreement between spherical and astigmatic refraction pre- and post-cycloplegia. Methods: We enrolled 96 patients (mean age: 12.5 ± 2.4 years), including 35 myopes, 30 emmetropes, and 31 hyperopes. Pre- and post-cycloplegia autorefraction and keratometry (Myopia Master) were conducted using 1% cyclopentolate. Ocular residual astigmatism (ORA) was calculated as the difference between refractive and keratometric astigmatism. Astigmatism was analyzed using Fourier analysis (J0 and J45). Results: Cycloplegia resulted in a more positive spherical equivalent (SE) (+0.80 D), with myopes showing the smallest (+0.38 D) and hyperopes showing the highest variation (+1.47 D) in SE. With-the-rule (WTR) astigmatism predominated in the refractive and keratometric measurements, while ORA was against-the-rule (ATR). Cycloplegia shifted the refractive J0 (+0.06 D) towards more WTR and decreased ORA J0 (+0.05 D). No effect was observed in the J45 component. About 25% of patients exhibited astigmatism changes above 0.25 D, with refractive J0 variation being positively correlated with accommodation relaxation (0.044 D per D of relaxation). Conclusion: Cycloplegia induces clinically significant changes in the spherical component, but minimal variations in astigmatic components, predominantly in hyperopic eyes, likely reflecting alterations in crystalline lens anatomy. Full article

Myopic eye growth induces mechanical stretch, which can lead to structural and functional retinal alterations. Here, we investigated the effect of lens-induced myopic growth on the distribution of retinal ganglion cells (RGCs), glial fibrillary acidic protein (GFAP) expression and intensity, and peripapillary retinal nerve fiber layer (ppRNFL) thickness in common marmosets (Callithrix jacchus) induced with myopia continuously for six months, using immunohistochemistry and spectral-domain optical coherence tomography. We also explored the relationship between cellular structural parameters and the photopic negative response (PhNR) using full-field electroretinography. Marmosets induced with myopia for six months developed axial myopia, had a thinner ppRNFL, reduced peripapillary ganglion cell (≈20%) and astrocyte density (≈42%), increased panretinal GFAP expression (≈42%) and nasal mid-periphery staining intensity (≈81%) compared to age-matched controls. Greater degrees of myopia and vitreous elongation were associated with reduced peripapillary RGCs and astrocyte density, and increased GFAP expression and intensity. These cellular structural changes did not show a significant relationship with the features of the PhNR, which remained unchanged. The outcomes of this study suggest that myopia induces a reorganization of the peripapillary inner retina at the cellular level that may not result in measurable functional repercussions at this stage of myopia development. Full article

Background: Myopia management contact lenses have been shown to successfully decrease the rate of eye elongation in children by changing the peripheral refractive profile of the retina. Despite the efforts of the scientific community, the retinal response mechanism to defocus is still unknown. The purpose of this study was to evaluate the local electrophysiological response of the retina with a myopia control contact lens (CL) compared to a single-vision CL of the same material. Methods: The retinal electrical activity and peripheral refraction of 16 eyes (16 subjects, 27.5 ± 5.7 years, 13 females and 3 males) with myopia between −0.75 D and −6.00 D (astigmatism < 1.00 D) were assessed with two CLs (Filcon 5B): a single-vision (SV) CL and an extended-depth-of-focus (EDOF) CL used for myopia management. The peripheral refraction was assessed with an open-field WAM-5500 auto-refractometer/keratometer in four meridians separated by 45° at 2.50 m distance. The global-flash multifocal electroretinogram (gf-mfERG) was recorded with the Reti-port/scan21 (Roland Consult) using a stimulus of 61 hexagons. The implicit time (in milliseconds) and response density (RD, in nV/deg²) of the direct (DC) and induced (IC) components were used for comparison between lenses in physiological pupil conditions. Results: Although the EDOF decreased both the HCVA and the LCVA (one and two lines, respectively; p < 0.003), it still allowed a good VA. The EDOF lens induced a myopic shift in most retinal areas, with a higher and statistically significant effect on the nasal retina. No differences in the implicit times of the DC and IC components were observed between SV and EDOF. Compared with the SV, the EDOF lens showed a higher RD in the IC component in the foveal region (p = 0.032). In the remaining retinal areas, the EDOF evoked lower, non-statistically significant RD in both the DC and IC components. Conclusions: The EDOF myopia control CL enhanced the response of the inner layers of the fovea. This might suggest that, besides other mechanisms potentially involved, the central foveal retinal activity might be involved in the mechanism of myopia control with these lenses. Full article

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia’s pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways. Full article

Purpose: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. Methods: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular −10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. Results: Mean interocular differences (treated—control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation. Full article

Purpose: The axial elongation in myopia is associated with some structural and functional retinal changes. The purpose of this study was to investigate the effect of a contact lens (CL) intended for myopia control on the choroidal thickness (ChT) and the retinal electrical response. Methods: Ten myopic eyes (10 subjects, 18–35 years of age) with spherical equivalents from −0.75 to −6.00 diopters (D) were enrolled. The ChT at different eccentricities (3 mm temporal, 1.5 mm temporal, sub-foveal ChT, 1.5 mm nasal, and 3 mm nasal), the photopic 3.0 b-wave of ffERG and the PERG were recorded and compared with two material-matched contact lenses following 30 min of wear: a single-vision CL (SV) and a radial power gradient CL with +1.50 D addition (PG). Results: Compared with the SV, the PG increased the ChT at all eccentricities, with statistically significant differences at 3.0 mm temporal (10.30 ± 11.51 µm, p = 0.020), in sub-foveal ChT (17.00 ± 20.01 µm, p = 0.025), and at 1.5 mm nasal (10.70 ± 14.50 µm, p = 0.044). The PG decreased significantly the SV amplitude of the ffERG photopic b-wave (11.80 (30.55) µV, p = 0.047), N35-P50 (0.90 (0.96) µV, p = 0.017), and P50-N95 (0.46 (2.50) µV, p = 0.047). The amplitude of the a-wave was negatively correlated with the ChT at 3.0T (r = −0.606, p = 0.038) and 1.5T (r = −0.748, p = 0.013), and the amplitude of the b-wave showed a negative correlation with the ChT at 1.5T (r = −0.693, p = 0.026). Conclusions: The PG increased the ChT in a similar magnitude observed in previous studies. These CLs attenuated the amplitude of the retinal response, possibly due to the combined effect of the induced peripheral defocus high-order aberrations impacting the central retinal image. The decrease in the response of bipolar and ganglion cells suggests a potential retrograde feedback signaling effect from the inner to outer retinal layers observed in previous studies. Full article

Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important role in pathological development. Herein, based on two miRNA datasets (GSE131831 and GSE84220), we aimed to reveal the general miRNA changes involved in myopia development. After a comparison of the differentially expressed miRNAs, miR-671-5p was identified as the common downregulated miRNA in the retina. miR-671-5p is highly conserved and related to 40.78% of the target genes of all downregulated miRNAs. Moreover, 584 target genes of miR-671-5p are related to myopia, from which we further identified 8 hub genes. Pathway analysis showed that these hub genes are enriched in visual learning and extra-nuclear estrogen signaling. Furthermore, two of the hub genes are also targeted by atropine, which strongly supports a key role of miR-671-5p in myopic development. Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development. Overall, our study identified the general regulatory role of miR-671-5p in myopia as well as its upstream and downstream mechanisms and provided novel treatment targets, which might inspire future studies. Full article

This study aims to explore the role of GABA_B receptors in the development of deprivation myopia (DM), lens-induced myopia (LIM) and lens-induced hyperopia (LIH). Chicks were intravitreally injected with 25 µg baclofen (GABA_BR agonist) in one eye and saline into the fellow eye. Choroidal thickness (ChT) was measured via OCT before and 2, 4, 6, 8, 24 h after injection. ChT decreased strongly at 6 and 8 h after baclofen injection and returned back to baseline level after 24 h. Moreover, chicks were monocularly treated with translucent diffusers, −7D or +7D lenses and randomly assigned to baclofen or saline treatment. DM chicks were injected daily into both eyes, while LIM and LIH chicks were monocularly injected into the lens-wearing eyes, for 4 days. Refractive error, axial length and ChT were measured before and after treatment. Dopamine and its metabolites were analyzed via HPLC. Baclofen significantly reduced the myopic shift and eye growth in DM and LIM eyes. However, it did not change ChT compared to respective saline-injected eyes. On the other hand, baclofen inhibited the hyperopic shift and choroidal thickening in LIH eyes. All the baclofen-injected eyes showed significantly lower vitreal DOPAC content. Since GABA is an inhibitory ubiquitous neurotransmitter, interfering with its signaling affects spatial retinal processing and therefore refractive error development with both diffusers and lenses. Full article

This study aimed to evaluate the peripheral defocus induced with a novel perifocal ophthalmic lens for myopia progression control and the potential impact on visual function. This experimental, non-dispensing crossover study evaluated 17 myopic young adults. The peripheral refraction was measured using an open-field autorefractor, at 2.50 m from the target point, in two eccentric points, 25° temporal, 25° nasal, and central vision. Visual contrast sensitivity (VCS) was measured at 3.00 m with a Vistech system VCTS 6500 in low light conditions. Light disturbance (LD) was assessed with a light distortion analyzer 2.00 m away from the device. Peripheral refraction, VCS, and LD were assessed with a monofocal lens and perifocal lens (with an add power of +2.50 D on the temporal side of the lens, and +2.00 D on the nasal side). The results showed that the perifocal lenses induced an average myopic defocus of −0.42 ± 0.38 D (p-value < 0.001) in the nasal retina, at 25° The changes induced by the lower add power in the nasal part of the lens did not induce statistically significant changes in the refraction of the temporal retina. The VCS and LD showed no significant differences between the monofocal and perifocal lenses. Full article

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions. Full article

To describe the effect of myopic eye growth on the structure and distribution of astrocytes, vasculature, and retinal nerve fiber layer thickness, which are critical for inner retinal tissue homeostasis and survival. Astrocyte and capillary distribution, retinal nerve fiber (RNFL), and ganglion cell layer (GCL) thicknesses were assessed using immunochemistry and spectral domain optical coherence tomography on eleven retinas of juvenile common marmosets (Callithrix Jacchus), six of which were induced with lens-induced myopia (refraction, Rx: −7.01 ± 1.8D). Five untreated age-matched juvenile marmoset retinas were used as controls (Rx: −0.74 ± 0.4D). Untreated marmoset eyes grew normally, their RNFL thickened and their astrocyte numbers were associated with RNFL thickness. Marmosets with induced myopia did not show this trend and, on the contrary, had reduced astrocyte numbers, increased GFAP-immunopositive staining, thinner RNFL, lower peripheral capillary branching, and increased numbers of string vessels. The myopic changes in retinal astrocytes, vasculature, and retinal nerve fiber layer thickness suggest a reorganization of the astrocyte and vascular templates during myopia development and progression. Whether these adaptations are beneficial or harmful to the retina remains to be investigated. Full article

The Retinal Ion-Driven Fluid Efflux (RIDE) model theorizes that phototransduction-driven changes in trans-retinal ion and fluid transport underlie the development of myopia (short-sightedness). In support of this model, previous functional studies have identified the attenuation of outer retinal contributions to the global flash electroretinogram (gfERG) following weeks of myopia induction in chicks, while discovery-driven transcriptome studies have identified changes to the expression of ATP-driven ion transport and mitochondrial metabolism genes in the retina/RPE/choroid at the mid- to late-induction time-points. Less is known about the early time-points despite biometric analyses demonstrating changes in eye growth by 3 h in the chick lens defocus model. Thus, the present study compared gfERG and transcriptome profiles between 3 h and 3 days of negative lens-induced myopia and positive lens-induced hyperopia in chicks. Photoreceptor (a-wave and d-wave) and bipolar (b-wave and late-stage d-wave) cell responses were suppressed following negative lens-wear, particularly at the 3–4 h and 3-day time-points when active shifts in the rate of ocular growth were expected. Transcriptome measures revealed the up-regulation of oxidative phosphorylation genes following 6 h of negative lens-wear, concordant with previous reports at 2 days in this model. Signal transduction pathways, with core genes involved in glutamate and G-protein coupled receptor signalling, were down-regulated at 6 h. These findings contribute to a growing body of evidence for the dysregulation of phototransduction and mitochondrial metabolism in animal models of myopia. Full article

Most of the previous myopic animal studies employed a single-candidate approach and lower resolution proteomics approaches that were difficult to detect minor changes, and generated limited systems-wide biological information. Hence, a complete picture of molecular events in the retina involving myopic development is lacking. Here, to investigate comprehensive retinal protein alternations and underlying molecular events in the early myopic stage, we performed a data-independent Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) based proteomic analysis coupled with different bioinformatics tools in pigmented guinea pigs after 4-day lens-induced myopia (LIM). Myopic eyes compared to untreated contralateral control eyes caused significant changes in refractive error and choroid thickness (p < 0.05, n = 5). Relative elongation of axial length and the vitreous chamber depth were also observed. Using pooled samples from all individuals (n = 10) to build a species-specific retinal ion library for SWATH analysis, 3202 non-redundant proteins (with 24,616 peptides) were identified at 1% global FDR. For quantitative analysis, the 10 individual retinal samples (5 pairs) were analyzed using a high resolution Triple-TOF 6600 mass spectrometry (MS) with technical replicates. In total, 37 up-regulated and 21 down-regulated proteins were found significantly changed after LIM treatment (log2 ratio (T/C) > 0.26 or < −0.26; p ≤ 0.05). Data are accepted via ProteomeXchange with identifier PXD025003. Through Ingenuity Pathways Analysis (IPA), “lipid metabolism” was found as the top function associated with the differentially expressed proteins. Based on the protein abundance and peptide sequences, expression patterns of two regulated proteins (SLC6A6 and PTGES2) identified in this pathway were further successfully validated with high confidence (p < 0.05) using a novel Multiple Reaction Monitoring (MRM) assay on a QTRAP 6500+ MS. In summary, through an integrated discovery and targeted proteomic approach, this study serves as the first report to detect and confirm novel retinal protein changes and significant biological functions in the early LIM mammalian guinea pigs. The study provides new workflow and insights for further research to myopia control. Full article

We compared the efficacy of controlling the annual increase in axial length (AL) in myopic Caucasian children based on two parameters: the back optic zone diameter (BOZD) of the orthokeratology (OK) lens and plus power ring diameter (PPRD) or mid-peripheral annular ring of corneal steepening. Data from 71 myopic patients (mean age, 13.34 ± 1.38 years; range, 10–15 years; 64% male) corrected with different BOZD OK lenses (DRL, Precilens) were collected retrospectively from a Spanish optometric clinic. The sample was divided into groups with BOZDs above or below 5.00 mm and the induced PPRD above or below 4.5 mm, and the relation to AL and refractive progression at 12 months was analyzed. Three subgroups were analyzed, i.e., plus power ring (PPR) inside, outside, or matching the pupil. The mean baseline myopia was −3.11 ± 1.46 D and the AL 24.65 ± 0.88 mm. Significant (p < 0.001) differences were found after 12 months of treatment in the refractive error and AL for the BOZD and PPRD. AL changes in subjects with smaller BOZDs decreased significantly regarding larger diameters (0.09 ± 0.12 and 0.15 ± 0.11 mm, respectively); in subjects with a horizontal sector of PPRD falling inside the pupil, the AL increased less (p = 0.035) than matching or outside the pupil groups by 0.04 ± 0.10 mm, 0.10 ± 0.11 mm, and 0.17 ± 0.12 mm, respectively. This means a 76% lesser AL growth or 0.13 mm/year in absolute reduction. OK corneal parameters can be modified by changing the OK lens designs, which affects myopia progression and AL elongation. Smaller BOZD induces a reduced PPRDs that slows AL elongation better than standard OK lenses. Further investigations should elucidate the effect of pupillary diameter, PPRD, and power change on myopia control. Full article