VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1^–/– mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1^–/– mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1^–/– pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1^–/– mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1^–/– choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion.

Purpose: To identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs. Methods: To induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore −10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes. Results: The CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-β signaling pathways. Conclusions: The results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.

Purpose: To evaluate the performance of a new formula of intraocular lens (IOL) power calculation (the O formula) based on ray tracing without commonly used parameters, including ultrasound-compatible axial length, keratometry readings, and A-constant. Setting: Tokyo Medical Center, Tokyo, Japan. Design: Retrospective consecutive case series. Methods: 423 eyes (423 patients) implanted with a single-piece, L-loop, acrylic IOL were enrolled. All biometric data for the O formula were obtained by anterior segment swept-source optical coherence tomography (SS-OCT) and SS-OCT–based biometer. The performance of the O formula was compared with those of the Barrett Universal II (BUII) and Kane formulas at 1 month postoperatively. Statistical analysis was applied according to a heteroscedastic test with SD of prediction errors as the main parameter for formula performance. Results: The SD of the O formula (0.426) was statistically significantly lower than that of the BUII formula (0.464, P = .034) but not statistically significantly different from that of the Kane formula (0.433, P = .601). The percentages of patients with refractive prediction errors within ±0.50 diopter (D) and ±1.00 D of the O, BUII, and Kane formulas were 75.4% and 98.6%, 77.1% and 97.9%, and 76.6% and 98.1%, respectively. Conclusions: The O formula, based on ray tracing using SS-OCT–based devices, is one of the promising approaches for IOL power calculation, although additional larger scale studies are needed. It may be used as an alternative in IOL power calculation because of its independence from commonly used parameters.

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.

To compare the refractive prediction accuracy of 13 intraocular lens (IOL) power calculation formulas, including 7 new-generation formulas available on the European Society of Cataract and Refractive Surgeons (ESCRS) calculator, in highly myopic eyes with axial lengths (AL) of 26.0 mm or longer, through a multicenter study in Japan. A retrospective case series. The study included 326 eyes of 326 patients at 4 surgical sites in Japan. All patients underwent comprehensive preoperative ophthalmic evaluations, including slit-lamp examination and fundoscopy by ophthalmologists. Corrected distance visual acuity and intraocular pressure were assessed by certified orthoptists. Standard phacoemulsification with intraocular lens implantation in the capsular bag was performed under topical anesthesia by experienced cataract surgeons. Postoperative spherical equivalent prediction error (SEQ-PE) was assessed for 13 formulas, including traditional formulas (Haigis, Hoffer Q, Holladay 1, SRK/T, Wang-Koch (WK) adjustment formulas for Holladay 1 [Holladay 1 WK] and SRK/T [SRK/T WK]) and new-generation formulas (Barrett Universal II, EVO 2.0, Hill-RBF, Hoffer QST, Kane, Cooke K6, Pearl-DGS). Predictive performance was evaluated using root-mean-square absolute error (RMSAE) and the Eyetemis online analysis tool. The mean AL was 27.28 ± 0.98 mm. The Hoffer QST, Holladay 1 WK, and SRK/T WK demonstrated myopic shifts, whereas other formulas showed a hyperopic shift in SEQ-PE. The Haigis, Hoffer Q, and Holladay 1 exhibited relatively large hyperopic errors (≥0.27 D). RMSAE exceeded 0.7 in the Hoffer Q and Holladay 1, whereas the best performance (RMSAE <0.53) was observed in the Holladay 1 WK and 6 new-generation formulas, except for the Pearl-DGS. New-generation IOL power calculation formulas and the Holladay 1 WK offer superior predictive accuracy in highly myopic eyes compared with traditional formulas.