Published papers

Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother’s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer’s solution was administered to the control group. We subjected the 4-week-old mice to −30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6–MMP-2 axis in mice.

We aimed to predict keratoconus progression and the need for corneal crosslinking (CXL) using deep learning (DL). Two hundred and seventy-four corneal tomography images taken by Pentacam HR® (Oculus, Wetzlar, Germany) of 158 keratoconus patients were examined. All patients were examined two times or more, and divided into two groups; the progression group and the non-progression group. An axial map of the frontal corneal plane, a pachymetry map, and a combination of these two maps at the initial examination were assessed according to the patients’ age. Training with a convolutional neural network on these learning data objects was conducted. Ninety eyes showed progression and 184 eyes showed no progression. The axial map, the pachymetry map, and their combination combined with patients’ age showed mean AUC values of 0.783, 0.784, and 0.814 (95% confidence interval (0.721–0.845) (0.722–0.846), and (0.755–0.872), respectively), with sen-sitivities of 87.8%, 77.8%, and 77.8% ((79.2–93.7), (67.8–85.9), and (67.8–85.9)) and specificities of 59.8%, 65.8%, and 69.6% ((52.3–66.9), (58.4–72.6), and (62.4–76.1)), respectively. Using the proposed DL neural network model, keratoconus progression can be predicted on corneal tomography maps combined with patients’ age.

Purpose To investigate refractive stability and characterize corneal incision repair up to 3 months after implantation of a new hydrophobic acrylic intraocular lens (IOL) with hydroxyethyl-methacrylate using a new automated IOL delivery system. Methods This prospective case series included 50 eyes of 50 patients undergoing phacoemulsification and implantation of the Clareon® CNA0T0 IOL using the AutonoMe® automated delivery system in the Department of Ophthalmology, Keio University School of Medicine. The clinical data were collected from 46 eyes of 46 patients preoperatively and 1 day, 1 week, and 1 and 3 months postoperatively. Endothelial-side incision gaping, posterior incision retraction, and Descemet’s membrane detachment were recorded as present or absent using anterior-segment optical coherence tomography postoperatively. Results The uncorrected distance and corrected distance visual acuities improved and stabilized 1 week postoperatively. The anterior chamber depth was stable from 1 week postoperatively. The subjective refraction was stable from 1 day postoperatively. Descemet’s membrane detachments and endothelial-side wound gaping were seen in 19 (41.3%) eyes and 34 (73.9%) eyes 1 day postoperatively and decreased gradually. Posterior incision retraction was seen in eight eyes (17.4%) on day 1 and increased to 19 eyes (41.3%) 3 months postoperatively. Conclusions The Clareon IOL had excellent refractive stability from day 1 postoperatively. The AutonoMe automated delivery system enables safe IOL implantation through a 2.4-mm corneal incision, although the wound required longer than 1 month to heal postoperatively.

The purpose of this study was to investigate the association between dry eye disease (DED) and myopia by evaluating higher order aberrations (HOAs) and choroidal thickness (CT). We recruited 72 myopic children with DED symptoms (mean age 12.8 years), measured the tear film breakup time (TBUT), corneal/intraocular/total ocular HOAs, CT, and axial length (AL), administered lifestyle questionnaires, and evaluated the relationships among TBUT, HOAs, CT, and AL. The TBUT was correlated significantly with the corneal HOAs and intraocular HOAs but not with the total ocular HOAs. Multiple regression analyses showed that the AL was associated significantly with the TBUT (β = − 0.067, P = 0.004), the intraocular HOAs, and total ocular HOAs but not with the corneal HOAs. The CT was associated significantly with the TBUT and AL (β = 9.15 and − 7.85, respectively; P < 0.001 and = 0.01, respectively). Our data suggested the association between DED and myopia might be independent of the HOAs. We showed that the TBUT was associated with the CT, which is related to the AL. Because the parasympathetic nervous system affects the lacrimal glands and CT, the parasympathetic nervous system might be a common upstream factor in the association between DED and myopia.

Although accumulating evidence suggests a higher prevalence of posterior vitreous detachment (PVD) in highly myopic eyes, the relation between ocular biometric features and PVD stages in such eyes remains unclear. Therefore, we enrolled 170 patients with high myopia (axial length ≥ 26.0 mm) to investigate the status of PVD regarding subfoveal choroidal thickness and axial length. Utilising swept-source optical coherence tomography, we classified the PVD status into five stages. The distribution of PVD grades increased as the choroidal thickness decreased and axial length increased (P < 0.01). On adjusting for age and sex, decreased choroidal thickness and increased axial length were associated with more advanced PVD stages: odds ratios with the highest vs. lowest groups were 0.31 (95% confidence interval [CI] 0.09–1.01; Ptrend = 0.009) for choroidal thickness and 5.16 (95% CI 1.34–19.80; Ptrend = 0.002) for axial length. The inverse association between choroidal thickness and PVD status seemed stronger in women than in men (Pinteraction = 0.05). In conclusion, we firstly observed a significant trend of decreased choroidal thickness, along with increased axial length, with increased grade of PVD, particularly among women with highly myopic eyes, suggesting that advanced morphological myopic changes contribute to PVD in middle-aged adults.

Purpose: To evaluate visual function in patients with early presbyopia using the functional visual acuity (FVA) test. Methods: This study included 27 eyes of 27 healthy older volunteers (mean age, 44.1 ± 2.6 years) and 14 eyes of 14 healthy young volunteers (mean age, 28.4±4.8 years). The distance-corrected visual acuity (DCVA), distance-corrected near VA (DCNVA), subjective amplitude of accommodation (AA), and distance and near pupillary diameters were measured. The distance FVA and distance-corrected near FVA (DCNFVA) were measured using the FVA Measurement System. The standard Schirmer test and standard tear break-up time measurement also were performed. Results: The logarithm of the minimum angle of resolution (logMAR) DCVA was better than 0 in all subjects. The percentages of subjects with logMAR DCNVA below 0 was significantly lower in the presbyopia group than in the young group. The DCNFVA in the presbyopia group was significantly (P <0.001) poorer than the DCNVA in that group. Significant linear negative correlations were seen between the DCNVA and AA (r = -0.507, P <0.001) and the DCNFVA and AA (r = -0.681, P <0.001) in the older subjects. Stepwise regression analysis showed that only the AA was a significant factor predictive of the DCNFVA in the presbyopia group. Tear function parameters were not adopted in the regression model. Conclusions: Measurement of the DCNFVA can detect decreased AA in early presbyopia better than measurement of the conventional near VA. The DCNFVA is a good index for early presbyopia.

© 2020, MDPI AG. All rights reserved. The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a −30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow. In conclusion, we suggest 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model.

© 2019 The Authors. The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments and the impact on patients. These outcomes were classified as primary (refractive error and/or axial length), secondary (patient reported outcomes and treatment compliance), and exploratory (peripheral refraction, accommodative changes, ocular alignment, pupil size, outdoor activity/ lighting levels, anterior and posterior segment imaging, and tissue biomechanics). The currently available instrumentation, which the literature has shown to best achieve the primary and secondary outcomes, was reviewed and critiqued. Issues relating to study design and patient selection were also identified. These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation development and to guide clinical trial protocols.