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1.
Graefes Arch Clin Exp Ophthalmol ; 262(6): 1839-1845, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38217766

ABSTRACT

PURPOSE: To assess the accuracy of intraocular lens (IOL) power formulas, namely, SRK/T, Haigis, Barrett Universal II, Barrett True-K for keratoconus, Kane formula, and Kane formula for keratoconus, for cataract with keratoconus in Japanese eyes. SETTING: Five surgical sites in Japan. DESIGN: A retrospective case series. METHODS: Eyes with keratoconus undergoing cataract surgery were included. Postoperative refraction was compared with the prediction by the formulas. Visual acuity, manifest spherical equivalent, prediction error (PE), and mean absolute errors (MAEs) were determined 1 month postoperatively. The PE within 0.50 diopter (D), 1.00 D, and 2.00 D were compared between IOL formulas. Subgroup analysis based on the steepest keratometry (stage 1, ≤ 48 D; stage 2, > 48 D and ≤ 53 D; and stage 3, > 53 D) was performed. The relationship between PE and preoperative biometric data were assessed. RESULTS: Fifty eyes were included. The MAE of the Barrett True-K for keratoconus, Kane keratoconus, and Kane formulas were significantly lower than that of Haigis. A statistically significant difference in the prediction accuracy within ± 0.50 D was found between Kane keratoconus and Haigis. The prediction accuracy of the Barrett True-K for keratoconus, SRK/T, and Kane within ± 1.00 D was statistically significant compared with that of Haigis. In stage 3, the Barrett True-K for keratoconus had a significantly lower MAE than SRK/T and Haigis. CONCLUSION: Keratoconus-specific formulas were more accurate than existing formulas in Japanese eyes. The Barrett True-K formula for keratoconus had higher prediction accuracy in severe keratoconus.


Subject(s)
Corneal Topography , Keratoconus , Lenses, Intraocular , Refraction, Ocular , Visual Acuity , Humans , Keratoconus/diagnosis , Keratoconus/physiopathology , Keratoconus/surgery , Retrospective Studies , Female , Japan/epidemiology , Refraction, Ocular/physiology , Male , Middle Aged , Reproducibility of Results , Corneal Topography/methods , Adult , Biometry/methods , Optics and Photonics , Aged , Cornea/pathology , Cornea/surgery , Follow-Up Studies
2.
J Cataract Refract Surg ; 50(5): 492-497, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38237070

ABSTRACT

PURPOSE: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas. SETTING: National Hospital Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance. RESULTS: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01). CONCLUSIONS: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.


Subject(s)
Axial Length, Eye , Biometry , Lenses, Intraocular , Optics and Photonics , Phacoemulsification , Refraction, Ocular , Tomography, Optical Coherence , Humans , Axial Length, Eye/pathology , Axial Length, Eye/diagnostic imaging , Retrospective Studies , Biometry/methods , Male , Female , Tomography, Optical Coherence/methods , Refraction, Ocular/physiology , Lens Implantation, Intraocular , Aged , Middle Aged , Aged, 80 and over , Visual Acuity/physiology , Pseudophakia/physiopathology
3.
J Clin Med ; 12(22)2023 Nov 07.
Article in English | MEDLINE | ID: mdl-38002573

ABSTRACT

PURPOSE: To evaluate the performance of traditional vergence formulas with segmented axial length (AL) compared to traditional composite AL in extremely long eyes, and to determine whether the segmented AL can be extended to the new-generation formulas, including the Barrett Universal II, Emmetropia Verifying Optical 2.0 (EVO2), Hill-RBF 3.0 (Hill3), Kane, and Ladas Super formula (LSF) formulas in extremely long eyes. SETTING: National Hospital. Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients who underwent uncomplicated cataract surgery implanted with a three-piece intraocular lens between December 2015 and March 2021 were retrospectively reviewed. The composite AL was measured with a swept-source optical coherence tomography (SS-OCT) biometer using a mean refractive index. The segmented AL was calculated by summing the geometric lengths of the ocular segments (cornea, aqueous, lens, and vitreous) using multiple specific refractive indices based on the data obtained by the SS-OCT-based biometer. When refraction was measured at three months postoperatively, the median absolute errors (MedAEs) were calculated with two ALs for each formula. RESULTS: The study included 31 eyes of 22 patients. The segmented AL (30.45 ± 1.23 mm) was significantly shorter than the composite AL (30.71 ± 1.28 mm, p < 0.001). The MedAEs were significantly reduced when using segmented AL for SRK/T, Haigis, Hill3, and LSF, compared to those obtained using composite AL (0.38 vs. 0.62, 0.48 vs. 0.79, 0.50 vs. 0.90, 0.34 vs. 0.61, p < 0.001 for all formulas, respectively). On the contrary, the MedAE obtained by Kane with segmented AL was significantly worse compared to the one with composite AL (0.35 vs. 0.27, p = 0.03). CONCLUSION: In extremely high myopic eyes, the segmented AL improves the performance of SRK/T, Haigis, Hill3, and LSF formulas compared to the composite AL, while the segmented AL worsens the prediction accuracy of the Kane formula.

4.
Biomolecules ; 13(9)2023 09 11.
Article in English | MEDLINE | ID: mdl-37759773

ABSTRACT

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.


Subject(s)
Myopia , Retinal Pigment Epithelium , Animals , Guinea Pigs , Bone Morphogenetic Protein 2/genetics , Choroid , Myopia/genetics
5.
Clin Ophthalmol ; 17: 2109-2124, 2023.
Article in English | MEDLINE | ID: mdl-37521152

ABSTRACT

Purpose: To obtain consensus on the key areas of burden associated with existing devices and to understand the requirements for a comprehensive next-generation diagnostic device to be able to solve current challenges and provide more accurate prediction of intraocular lens (IOL) power and presbyopia correction IOL success. Patients and Methods: Thirteen expert refractive cataract surgeons including three steering committee (SC) members constituted the voting panel. Three rounds of voting included a Round 1 structured electronic questionnaire, Round 2 virtual face-to-face meeting, and Round 3 electronic questionnaire to obtain consensus on topics related to current limitations and future solutions for preoperative cataract-refractive diagnostic devices. Results: Forty statements reached consensus including current limitations (n = 17) and potential solutions (n = 23) associated with preoperative diagnostic devices. Consistent with existing evidence, the panel reported unmet needs in measurement accuracy and validation, IOL power prediction, workflow, training, and surgical planning. A device that facilitates more accurate corneal measurement, effective IOL power prediction formulas for atypical eyes, simplified staff training, and improved decision-making process for surgeons regarding IOL selection is expected to help alleviate current burdens. Conclusion: Using a modified Delphi process, consensus was achieved on key unmet needs of existing preoperative diagnostic devices and requirements for a comprehensive next-generation device to provide better objective and subjective outcomes for surgeons, technicians, and patients.

6.
J Vis Exp ; (195)2023 05 09.
Article in English | MEDLINE | ID: mdl-37246877

ABSTRACT

This protocol describes the isolation of cells of the retinal pigment epithelium (RPE) from the eyes of young pigmented guinea pigs for potential application in molecular biology studies, including gene expression analyses. In the context of eye growth regulation and myopia, the RPE likely plays a role as a cellular relay for growth modulatory signals, as it is located between the retina and the two walls of the eye, such as the choroid and sclera. While protocols for isolating the RPE have been developed for both chicks and mice, these protocols have proven not to be directly translatable to the guinea pig, which has become an important and widely used mammalian myopia model. In this study, molecular biology tools were used to examine the expression of specific genes to confirm that the samples were free of contamination from the adjacent tissues. The value of this protocol has already been demonstrated in an RNA-Seq study of RPE from young pigmented guinea pigs exposed to myopia-inducing optical defocus. Beyond eye growth regulation, this protocol has other potential applications in studies of retinal diseases, including myopic maculopathy, one of the leading causes of blindness in myopes, in which the RPE has been implicated. The main advantage of this technique is that it is relatively simple and once perfected, yields high-quality RPE samples suitable for molecular biology studies, including RNA analysis.


Subject(s)
Myopia , Retina , Animals , Guinea Pigs , Epithelial Cells/metabolism , Mammals , Myopia/genetics , Myopia/metabolism , Retina/metabolism , Retinal Pigment Epithelium/metabolism , Retinal Pigments/metabolism
7.
PLoS One ; 17(8): e0273431, 2022.
Article in English | MEDLINE | ID: mdl-36040874

ABSTRACT

PURPOSE: To compare the change in intraocular lens (IOL) axial movement, corneal power, and postoperative refraction of eyes implanted with two different single-piece, open loop, acrylic foldable IOLs with planar-haptic design: one IOL with hinges vs. one IOL without hinges. The role of IOL axial movement on short-term refractive shift after cataract surgery was also evaluated. METHODS: This retrospective comparative study enrolled consecutive patients who had phacoemulsification with aspheric IOL implantation. The IOL depth (the distance from corneal endothelium to IOL surface) and corneal power were measured via anterior-segment optical coherence tomography at 4 days and 1 month postoperatively. The changes in axial movement of the IOL, corneal power, and manifest refractive spherical equivalent (MRSE) were compared among groups, and the correlations between each lens were evaluated. RESULTS: IOL with hinges was implanted in 42 eyes of 42 patients and IOL without hinges was implanted in 42 eyes of 42 patients. The change in axial movement between 4 days and 1 month was significantly smaller in the IOL with hinges group than in the IOL without hinges group (p < 0.001). The axial movement of IOL with hinges did not correlate with the MRSE change; however, the forward shift of IOL without hinges correlated with the myopic refractive change (Pearson r = 0.62, p < 0.001). CONCLUSION: The postoperative axial movement of IOL was more stable in the IOL with hinges group than the IOL without hinges group between 4 days and 1 month after cataract surgery. Even though the two study IOLs with planar-haptic design are made of similar acrylic materials, other characteristics such as hinge structure may affect IOL stability in the bag.


Subject(s)
Cataract , Lenses, Intraocular , Phacoemulsification , Humans , Lens Implantation, Intraocular/methods , Phacoemulsification/methods , Prospective Studies , Prosthesis Design , Refraction, Ocular , Retrospective Studies
8.
Invest Ophthalmol Vis Sci ; 63(9): 25, 2022 08 02.
Article in English | MEDLINE | ID: mdl-36006019

ABSTRACT

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-ß 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.


Subject(s)
Contact Lenses , Myopia , Animals , Contact Lenses/adverse effects , Disease Models, Animal , Guinea Pigs , Myopia/genetics , Myopia/metabolism , Retinal Pigment Epithelium/metabolism , Retinal Pigments/metabolism , Transcriptome
9.
J Cataract Refract Surg ; 48(11): 1305-1311, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35642086

ABSTRACT

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.


Subject(s)
Lenses, Intraocular , Phacoemulsification , Refractive Errors , Humans , Phacoemulsification/methods , Retrospective Studies , Biometry/methods , Optics and Photonics , Refraction, Ocular , Axial Length, Eye
10.
Transl Vis Sci Technol ; 11(3): 26, 2022 03 02.
Article in English | MEDLINE | ID: mdl-35323888

ABSTRACT

Purpose: This study compared the efficacy of topical 1% atropine applied daily versus every 3 days for controlling myopia progression in guinea pigs. Methods: To induce myopia, pigmented guinea pigs (New Zealand strain, n = 38) wore monocular -10 D rigid gas-permeable (RGP) contact lenses, which were replaced after 3 weeks with -15 diopter (D) contact lenses. Animals were treated with 1% atropine either daily (Atr-QD; n = 12), or every 3 days (Atr-Q3D; n = 11), or with artificial tears (control group; n = 15). Spherical equivalent refractive error (SER) and axial length (AL) data, as well as retinal and choroidal thickness data were collected weekly. Results: Whereas mean (±SEM) interocular differences (treated - fellow) in both SER and AL at week 0 (baseline) were similar for all groups, significant differences between the atropine-treated and control groups were evident by week 6 (SER and AL, P < 0.001). The treated eyes of the control group showed relatively more axial elongation and myopia progression than both the Atr-QD and Atr-Q3D groups. Choroidal blood vessel area also decreased over time in the treated eyes of the control group, coupled with choroidal thinning overall, with these changes being attenuated by atropine. Retinal thickness showed a developmental decrease over the treatment period but was unaffected by atropine. Conclusions: For this defocus-induced guinea pig model of myopia, application of 1% topical atropine slows myopia progression, even when applied every 3 days. Translational Relevance: The results from this study suggest that the frequency of dosing for topical atropine may be reduced from the widely used daily dosing regimen without loss of myopia control efficacy.


Subject(s)
Contact Lenses , Myopia , Animals , Atropine , Choroid , Guinea Pigs , Myopia/drug therapy , Retina
11.
Ophthalmology ; 128(11): e142-e152, 2021 11.
Article in English | MEDLINE | ID: mdl-33221325

ABSTRACT

The purpose of this review is to evaluate the usefulness of corneal topography to select premium intraocular lenses (IOLs), including aspherical IOLs, toric IOLs, and multifocal IOLs, in refractive cataract surgery. Corneal topography can detect corneal regular astigmatism, corneal irregular astigmatism (higher-order aberrations [HOAs]) including spherical aberration, and corneal shape abnormalities after corneal refractive surgery. Surgeons can explain to the patients with significant corneal HOAs about its effect on postoperative visual function before surgery. Multifocal IOLs should not be selected for such eyes. For eyes with abnormal corneal shape, appropriate IOL power calculation formulae can be applied. In the case of toric IOLs, regular astigmatism and corneal HOAs should be checked. Before implanting an aspheric IOL, it is ideal to confirm spherical aberration of the cornea is not below the normal range. Because corneal HOAs, abnormal corneal shape after corneal refractive surgery, corneal regular astigmatism, and corneal spherical aberration increase postoperative refractive errors and poor vision quality with premium IOLs, corneal topography before cataract surgery is helpful in screening patients who are not appropriate candidates for premium IOLs.


Subject(s)
Cataract Extraction , Cornea/diagnostic imaging , Corneal Topography/methods , Lenses, Intraocular , Refraction, Ocular/physiology , Refractive Surgical Procedures , Cornea/surgery , Humans
12.
J Cataract Refract Surg ; 46(5): 710-715, 2020 May.
Article in English | MEDLINE | ID: mdl-32358265

ABSTRACT

PURPOSE: To compare the changes in axial length (AL) obtained after cataract surgery by partial coherence interferometry (PCI), swept-source optical coherence tomography with the composite method (SS-OCT/CM), and SS-OCT with the segmental method (SS-OCT/SM). SETTING: National Hospital Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: AL was measured preoperatively and 1 month postoperatively by PCI, SS-OCT/CM, and SS-OCT/SM. RESULTS: Two hundred sixty-eight eyes in 139 patients who underwent cataract surgery were included. The mean ALs measured by PCI and SS-OCT/CM decreased significantly from 24.14 ± 1.58 to 24.05 ± 1.58 mm (P < .0001) and from 24.15 ± 1.58 to 24.05 ± 1.59 mm (P < .0001), respectively. The mean differences between the preoperative and postoperative AL were 0.083 ± 0.044 mm (PCI) and 0.096 ± 0.045 mm (SS-OCT/CM), respectively; Bland-Altman analysis revealed fixed bias between the preoperative and postoperative values. The mean preoperative and postoperative ALs measured by SS-OCT/SM were 24.12 ± 1.54 and 24.12 ± 1.54 mm, respectively (P = 0.97). The mean difference between the preoperative and postoperative ALs was 0.00 ± 0.03 mm on SS-OCT/SM; Bland-Altman analysis indicated good agreement between these values. CONCLUSIONS: The difference between preoperative and postoperative ALs is less with SS-OCT/SM than with PCI or SS-OCT/CM. Assuming that AL is not altered by cataract surgery, AL measurement is more accurate by SS-OCT/SM than by PCI or SS-OCT/CM.


Subject(s)
Biometry , Cataract , Axial Length, Eye , Humans , Japan , Reproducibility of Results , Retrospective Studies , Tomography, Optical Coherence
13.
Sci Rep ; 10(1): 4474, 2020 03 11.
Article in English | MEDLINE | ID: mdl-32161358

ABSTRACT

This study compared the optical axial length (AL) obtained by composite and segmental methods using swept-source optical coherence tomography (SS-OCT) devices, and demonstrated its effects on the post-operative refractive errors (RE) one month after cataract surgery. Conventional AL measured with the composite method used the mean refractive index. The segmented-AL method used individual refractive indices for each ocular medium. The composite AL (24.52 ± 2.03 mm) was significantly longer (P < 0.001) than the segmented AL (24.49 ± 1.97 mm) among a total of 374 eyes of 374 patients. Bland-Altman analysis revealed a negative proportional bias for the differences between composite and segmented ALs. Although there was no significant difference in the RE obtained by the composite and segmental methods (0.42 ± 0.38 D vs 0.41 ± 0.36 D, respectively, P = 0.35), subgroup analysis of extremely long eyes implanted with a low power intraocular lens indicated that predicted RE was significantly smaller with the segmental method (0.45 ± 0.86 D) than that with the composite method (0.80 ± 0.86 D, P < 0.001). Segmented AL with SS-OCT is more accurate than composite AL in eyes with extremely long AL and can improve post-operative hyperopic shifts in such eyes.

14.
Stem Cell Reports ; 13(4): 761-774, 2019 10 08.
Article in English | MEDLINE | ID: mdl-31564644

ABSTRACT

The first-in-human trial of induced pluripotent stem cell (iPSC)-based autologous transplantation was successfully performed on a female patient with age-related macular degeneration. Here we delineated the base-resolution methylome of the iPSC-derived retinal pigment epithelium (iRPE) used in this trial. The methylome of iRPE closely resembled that of native RPE (nRPE), although partially methylated domains (PMDs) emerged in iRPE but not nRPE. Most differentially methylated regions between iRPE and nRPE appeared to originate from (de)methylation errors during differentiation, whereas errors at reprogramming resulted in aberrant genomic imprinting and X chromosome reactivation. Moreover, non-CpG methylation was prominent in nRPE but not iRPE. Intriguingly, xenotransplantation to mouse remodeled the iRPE methylome to demethylate a subset of suppressed genes and accumulate non-CpG methylation, but failed to resolve PMDs and hypermethylated CpG islands. Although the impacts of these alterations remain elusive, our findings should provide a useful guide for methylome analyses of other iPSC-derived cells.


Subject(s)
Epigenome , Epithelial Cells/cytology , Epithelial Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Retinal Pigment Epithelium/cytology , Stem Cell Transplantation , Cellular Reprogramming , Computational Biology/methods , CpG Islands , DNA Methylation , Humans , Macular Degeneration/etiology , Macular Degeneration/metabolism , Macular Degeneration/therapy , Transplantation, Autologous , Whole Genome Sequencing
15.
Elife ; 72018 04 03.
Article in English | MEDLINE | ID: mdl-29609731

ABSTRACT

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.


Subject(s)
Aldehyde Dehydrogenase/metabolism , Choroid/physiology , Gene Expression Regulation , Neovascularization, Physiologic , Retinal Pigment Epithelium/physiology , SOX9 Transcription Factor/metabolism , Vascular Endothelial Growth Factor A/metabolism , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase 1 Family , Animals , Epithelial Cells/physiology , Mice, Inbred C57BL , Mice, Knockout , Retinal Dehydrogenase , Tretinoin/metabolism
17.
Ophthalmology ; 124(6): e54, 2017 06.
Article in English | MEDLINE | ID: mdl-28528841
18.
Ophthalmology ; 123(12): 2474-2480, 2016 12.
Article in English | MEDLINE | ID: mdl-27769585

ABSTRACT

PURPOSE: To evaluate the accuracy of a new formula for predicting postoperative anterior chamber depth (ACD) with preoperative angle-to-angle (ATA) depth using anterior segment (AS) optical coherence tomography (OCT) and to compare it with established methods. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Three hundred four eyes (276 patients) implanted with acrylic intraocular lenses (IOLs) were divided randomly into a training set (152 eyes) and a validation set (152 eyes). METHODS: Based on the training set data, the postoperative ACD measured 1 month after surgery was analyzed via multiple linear regression analysis with 5 preoperatively measured variables: ATA depth, ATA width, preoperative ACD measured with AS OCT, axial length (AL), and corneal power. A new regression formula for predicting postoperative ACD was developed using the results of the stepwise analysis. In the validation set data, the coefficients of determination (R2) between the measured postoperative ACD and the predicted postoperative ACD obtained using the new formula were compared with those obtained using the Sanders-Retzlaff-Kraff theoretic (SRK/T) and Haigis formulas. The absolute prediction errors were compared with each formula. MAIN OUTCOME MEASURES: Postoperative ACD, median absolute prediction error of postoperative ACD, and ocular biometric parameters. RESULTS: In the training set, ATA depth yielded the highest standard partial regression coefficient value, indicating that ATA depth is the most effective parameter for predicting postoperative ACD. The new regression formula was developed with 3 variables; ATA depth, preoperative ACD, and AL. In the validation set, the postoperative ACDs of the new formula, the SRK/T formula, and Haigis formula were predicted with R2 of 0.71, 0.36, and 0.55, respectively, and the medians of the absolute prediction errors were 0.10 mm, 0.65 mm, and 0.30 mm, respectively. The absolute prediction error with the new formula was significantly smaller than those obtained with the SRK/T and Haigis formulas (P < 0.0001). CONCLUSIONS: The new formula with 3 preoperative parameters-ATA depth, preoperative ACD, and AL-predicted postoperative ACD more accurately than the SRK/T and Haigis formulas. It may be possible to improve the accuracy of IOL power calculation using an improved postoperative ACD prediction with the ATA depth measured by AS OCT.


Subject(s)
Algorithms , Anterior Chamber/pathology , Lenses, Intraocular , Tomography, Optical Coherence/methods , Aged , Aged, 80 and over , Anterior Chamber/diagnostic imaging , Biometry/methods , Cataract Extraction , Ciliary Body/diagnostic imaging , Ciliary Body/pathology , Female , Humans , Iris/diagnostic imaging , Iris/pathology , Lens Implantation, Intraocular , Male , Middle Aged , Optics and Photonics , Postoperative Period , Regression Analysis , Reproducibility of Results , Retrospective Studies , Trabecular Meshwork/diagnostic imaging , Trabecular Meshwork/pathology
19.
Retina ; 35(3): 429-34, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25166271

ABSTRACT

PURPOSE: To compare the long-term outcomes of simple hemorrhage (SH) without any treatments and myopic choroidal neovascularization (mCNV) treated with intravitreal bevacizumab in highly myopic eyes. METHODS: Twenty eyes (17 patients) with SH and 28 eyes (27 patients) with mCNV were included. We retrospectively evaluated the refractive error, axial length, age, best-corrected visual acuity, and the integrity of photoreceptor inner segment/outer segment junction and compared the two groups. RESULTS: The mean patient age was 41.6 ± 11.2 years, the mean refractive error -12.7 ± 3.57 diopters, and the mean axial length was 29.64 ± 1.42 mm. Patients in the SH group were significantly (P < 0.001) younger than those in the mCNV group (34.8 vs. 46.5 years, respectively). There were no significant differences in other parameters between the groups. Compared with baseline, the best-corrected visual acuity improved significantly (P < 0.01) at 12 months in both groups. The change in vision at 12 months in the SH group was significantly (P < 0.05) better than that in the mCNV group, although there were no significant differences at 3 months or 6 months. The final integrity of photoreceptor inner segment/outer segment junction was significantly associated with the final best-corrected visual acuity (P < 0.05). CONCLUSION: Eyes with SH had a more favorable visual prognosis compared with eyes with mCNV treated with intravitreal bevacizumab. The differential diagnosis of these pathologies is important.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Choroidal Neovascularization/drug therapy , Myopia, Degenerative/complications , Retinal Hemorrhage/physiopathology , Visual Acuity/physiology , Adolescent , Adult , Axial Length, Eye/pathology , Bevacizumab , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/physiopathology , Coloring Agents , Female , Fluorescein Angiography , Follow-Up Studies , Humans , Indocyanine Green , Intravitreal Injections , Male , Middle Aged , Prognosis , Refractive Errors/physiopathology , Retrospective Studies , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors
20.
J Cataract Refract Surg ; 39(8): 1267-70, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23796622

ABSTRACT

We report an unusual case of a 28-year-old man who developed interface fluid with herpetic keratouveitis and elevated intraocular pressure (IOP) after laser in situ keratomileusis (LASIK) in the left eye. The IOP was unmeasurable with the Goldmann applanation tonometer; rebound tonometry showed an IOP of 30 mm Hg in the central cornea and 58 mm Hg in the superior cornea. Medical treatment of the elevated IOP resulted in resolution of the accumulated interface fluid. This case highlights the inaccuracy of IOP measurements in the central cornea with interface fluid or central corneal edema caused by elevated IOP after LASIK and shows the efficacy of IOP measurements at the peripheral cornea using rebound tonometry. It also shows that uveitis can be a risk factor for interface fluid syndrome after LASIK.


Subject(s)
Body Fluids , Corneal Edema/etiology , Keratitis, Herpetic/etiology , Keratomileusis, Laser In Situ/adverse effects , Lasers, Excimer , Uveitis, Anterior/etiology , Adult , Corneal Edema/diagnosis , Corneal Edema/drug therapy , Humans , Intraocular Pressure , Male , Myopia/surgery , Ocular Hypertension/etiology , Tomography, Optical Coherence , Tonometry, Ocular , Visual Acuity
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