Sclera

Axial length is the primary determinant of eye size, and it is elongated in myopia. However, the underlying mechanism of the onset and progression of axial elongation remain unclear. Here, we show that endoplasmic reticulum (ER) stress in sclera is an essential regulator of axial elongation in myopia development through activation of both PERK and ATF6 axis followed by scleral collagen remodeling. Mice with lens-induced myopia (LIM) showed ER stress in sclera. Pharmacological interventions for ER stress could induce or inhibit myopia progression. LIM activated all IRE1, PERK and ATF6 axis, and pharmacological inhibition of both PERK and ATF6 suppressed myopia progression, which was confirmed by knocking down above two genes via CRISPR/Cas9 system. LIM dramatically changed the expression of scleral collagen genes responsible for ER stress. Furthermore, collagen fiber thinning and expression of dysregulated collagens in LIM were ameliorated by 4-PBA administration. We demonstrate that scleral ER stress and PERK/ATF6 pathway controls axial elongation during the myopia development in vivo model and 4-PBA eye drop is promising drug for myopia suppression/treatment.

PurposeThe sclera is believed to biomechanically influence eye size, facilitating the excessive axial elongation that occurs during myopigenesis. Here, we test the hypothesis that the sclera will be remodeled and exhibit altered biomechanics in the mouse model of form-deprivation (FD) myopia, accompanied by altered retinoid concentrations, a potential signaling molecule involved in the process.MethodsMale C57 Bl/6J mice were subjected to unilateral FD (n = 44 eyes), leaving the contralateral eye untreated (contra; n = 44). Refractive error and ocular biometry were measured in vivo prior to and after 1 or 3 weeks of FD. Ex vivo measurements were made of scleral biomechanical properties (unconfined compression: n = 24), scleral sulfated glycosaminoglycan (sGAG) content (dimethylmethylene blue: n = 18, and immunohistochemistry: n = 22), and ocular all-trans retinoic acid (atRA) concentrations (retina and RPE + choroid + sclera, n = 24). Age-matched naïve controls were included for some outcomes (n = 32 eyes).ResultsSignificant myopia developed after 1 (-2.4 ± 1.1 diopters [D], P ConclusionsWe report that biomechanics and GAG content of the mouse sclera are altered during myopigenesis. All scleral outcomes generally follow the trends found in other species and support a retina-to-sclera signaling cascade underlying mouse myopigenesis.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

PurposePersistent corneal oedema can lead to reduced visual performance and longer-term ocular complications in eyes with reduced endothelial cell function. The aim of this study was to quantify the effect of incorporating limbal scleral lens fenestrations on central corneal oedema.MethodsTwenty young healthy adults (mean age ± standard deviation 32 ± 11 years) with normal corneas wore non-fenestrated and fenestrated (3 × 1 mm limbal fenestrations separated by 120°) OneFitMed+ scleral lenses in both eyes (on separate days) for 3 h. All other scleral lens parameters were held constant except for the addition of the fenestrations. Central fluid reservoir thickness and corneal oedema were quantified using optical coherence tomography, and corrections were made for small thickness variations between lens conditions.ResultsThe corrected central corneal oedema was significantly reduced following fenestrated lens wear (0.80 ± 0.93%) compared to non-fenestrated lens wear (1.32 ± 0.81%; a 39% relative reduction, p = 0.02). The reduction in central corneal oedema with the fenestrated lens was slightly greater for participants without an air bubble in the fluid reservoir (n = 10, 0.73 ± 0.80% less oedema, 45% relative reduction) compared to those with an air bubble (n = 10, 0.30 ± 1.05% less oedema, 30% relative reduction) but was not statistically significant (p = 0.31).ConclusionThe incorporation of three 1 mm diameter limbal fenestrations separated by 120° reduced the magnitude of central corneal oedema by 39% on average in healthy eyes compared to a non-fenestrated scleral lens. A reduction in central corneal oedema was still observed without the presence of an air bubble within the fluid reservoir. Future studies investigating the long-term efficacy of different fenestration configurations in clinical populations are warranted.Clinical trialThis study was registered on the Australian New Zealand Clinical Trials Registry (Registration number 12622001164785p), date of registration 24 August, 2022.