Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia.

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.

Lens-induced myopization and intraocular pressure in young guinea pigs.

BACKGROUND: Intraocular pressure (IOP) is an important physiological measure of the eye and is associated with some ocular disorders. We aimed to assess the influence of topical beta blocker-induced IOP reduction on lens-induced axial elongation in young guinea pigs. METHODS: The experimental study included 20 pigmented guinea pigs (age: 2-3 weeks). Myopia was induced in the right eyes for 5 weeks with - 10 diopter lenses. The right eyes additionally received either one drop of carteolol 2% (study group, n = 10) or one drop of artificial tears daily (control group, n = 10), while the contralateral eyes of all animals remained untouched. The outcome parameter was axial elongation during the follow-up period. The mean of all IOP measurements taken during the study was referred to as mean IOP. RESULTS: Greater axial elongation was associated with a shorter axial length at baseline (P < 0.001; standardized regression coefficient beta: - 0.54) and lens-induced myopization (P < 0.001; beta: 0.55). In the multivariable model, axial elongation was not significantly correlated with the IOP at study end (P = 0.59), the mean IOP during the study period (P = 0.12), the mean of all IOP measurements (P = 0.17), the difference between the IOP at study end and baseline IOP (P = 0.38), the difference between the mean IOP during the study period and the baseline IOP (P = 0.11), or the application of carteolol eye drops versus artificial tears eye drops (P = 0.07). The univariate analysis of the relationships between axial elongation and the IOP parameters yielded similar results. The inter-eye difference between the right eye and the left eye in axial elongation was significantly associated with the inter-eye difference in baseline axial length (P = 0.001; beta:-0.67) but not significantly correlated with the inter-eye difference in any of the IOP-related parameters (all P > 0.25). CONCLUSIONS: In young guinea pigs with or without lens-induced axial elongation, neither the physiological IOP nor the IOP reduced by carteolol, a topical beta-blocker, was associated with the magnitude of axial elongation. These results suggest that IOP, regardless of whether it is influenced by carteolol, does not play a major role in axial elongation in young guinea pigs.

In vivo Imaging of Retina and Choroid in Guinea Pigs.

Purpose: To evaluate the feasibility of in-vivo imaging of the retina and choroid using spectral domain optical coherence tomography (OCT) in guinea pigs. Methods: The study included 19 pigmented guinea pigs (age: 3-4 weeks) which underwent sonographic axial length measurements and OCT imaging. At study end, the animals were sacrificed and histomorphometric examinations of the retina and choroid were performed. We assessed the reproducibility of the OCT measurements and compared in-vivo measurements to histomorphometric data. Results: The mean thickness of the retina and choroid near the optic nerve head was 175.6 ± 25.8 and 63.4 ± 16.5 µm, respectively, and mean Bruch's membrane opening (BMO) diameter was 831 ± 121 µm. The intra-observer comparison of measurements of retinal thickness (intraclass correlation coefficient (ICC) = 0.92, 95% CI: 0.86-0.96; P < 0.001), choroidal thickness (ICC = 0.92, 95% CI: 0.86-0.96; P < 0.001), and BMO diameter (ICC = 0.92, 95% CI: 0.86-0.96; P < 0.001) showed a high correlation. A high agreement was present also for the inter-observer reproducibility of the measurements of retinal thickness (Pearson correlation coefficient (R) = 0.98; P < 0.001), choroidal thickness (R = 0.96; P < 0.001), and BMO diameter (R = 0.98; P < 0.001). The Bland-Altman plots showed that 2.6% (1/38), 5.3% (2/38), and 7.9% (3/38) of the measurement points of retinal thickness, choroidal thickness and BMO diameter, respectively, were located outside of the 95% limits of agreement. The OCT-based thickness measurements of retina and choroid were significantly higher than those measured by histomorphometry (both P-values <0.01). Conclusion: OCT-based in-vivo morphometric imaging of the retina and choroid in guinea pigs is feasible with an acceptable intra-observer repeatability and inter-observer reproducibility.

Deep Learning-Based Estimation of Axial Length and Subfoveal Choroidal Thickness From Color Fundus Photographs.

This study aimed to develop an automated computer-based algorithm to estimate axial length and subfoveal choroidal thickness (SFCT) based on color fundus photographs. In the population-based Beijing Eye Study 2011, we took fundus photographs and measured SFCT by optical coherence tomography (OCT) and axial length by optical low-coherence reflectometry. Using 6394 color fundus images taken from 3468 participants, we trained and evaluated a deep-learning-based algorithm for estimation of axial length and SFCT. The algorithm had a mean absolute error (MAE) for estimating axial length and SFCT of 0.56 mm [95% confidence interval (CI): 0.53,0.61] and 49.20 µm (95% CI: 45.83,52.54), respectively. Estimated values and measured data showed coefficients of determination of r 2 = 0.59 (95% CI: 0.50,0.65) for axial length and r 2 = 0.62 (95% CI: 0.57,0.67) for SFCT. Bland-Altman plots revealed a mean difference in axial length and SFCT of -0.16 mm (95% CI: -1.60,1.27 mm) and of -4.40 µm (95% CI, -131.8,122.9 µm), respectively. For the estimation of axial length, heat map analysis showed that signals predominantly from overall of the macular region, the foveal region, and the extrafoveal region were used in the eyes with an axial length of < 22 mm, 22-26 mm, and > 26 mm, respectively. For the estimation of SFCT, the convolutional neural network (CNN) used mostly the central part of the macular region, the fovea or perifovea, independently of the SFCT. Our study shows that deep-learning-based algorithms may be helpful in estimating axial length and SFCT based on conventional color fundus images. They may be a further step in the semiautomatic assessment of the eye.