Efficient and robust induction of retinal pigment epithelium cells by tankyrase inhibition regardless of the differentiation propensity of human induced pluripotent stem cells.

Transplantation of retinal pigment epithelium (RPE) cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) hold great promise as a new therapeutic modality for age-related macular degeneration and Stargardt disease. The development of hESC/hiPSC-derived RPE cells as cell-based therapeutic products requires a robust, scalable production for every hiPSC line congruent for patients. However, individual hESC/hiPSC lines show bias in differentiation. Here we report an efficient, robust method that induces RPE cells regardless of the differentiation propensity of the hiPSC lines. Application of the tankyrase inhibitor IWR-1-endo, which potentially inhibits Wnt signaling, promoted retinal differentiation in dissociated hiPSCs under feeder-free, two-dimensional culture conditions. The other tankyrase inhibitor, XAV939, also promoted retinal differentiation. However, Wnt signaling inhibitors, IWP-2 and iCRT3, that target porcupine and ß-catenin/TCF, respectively, did not. Further treatment with the GSK3ß inhibitor CHIR99021 and FGF receptor inhibitor SU5402 induced hexagonal pigmented cells with phagocytotic ability. Notably, the IWR-1-endo-based differentiation method induced RPE cells even in an hiPSC line that expresses a lower level of the differentiation propensity marker SALL3, which is indicative of resistance to ectoderm differentiation. The present study demonstrated that tankyrase inhibitors cause efficient and robust RPE differentiation, irrespective of the SALL3 expression levels in hiPSC lines. This differentiation method will resolve line-to-line variations of hiPSCs in RPE production and facilitate clinical application and industrialization of RPE cell products for regenerative medicine.

Flanged fixation: Yamane technique and its application.

PURPOSE OF REVIEW: To review variations of flanged intraocular lens fixation (Yamane technique) and their outcomes. RECENT FINDINGS: Sutureless intrascleral IOL fixation has become popular, and many techniques have been reported. Among them, the Yamane technique has been widely used in recent years, and there are many variations. However, there are no reports that systematically compare them. SUMMARY: There are variations of the Yamane technique, such as those used to create a scleral tunnel or to dock needles and haptics. Although few reports have directly compared each technique, small scleral wounds appear to be beneficial for long-term stability of the IOL. A method of fixing a capsule tension segment or iris using a flange has also been reported, demonstrating the diverse range of uses of the flange.

One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy.

PURPOSE: To identify the functional outcome and evaluate the morphologic changes of patients with pachychoroid neovasculopathy (PNV) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) at the 1-year follow-up. METHODS: We retrospectively studied all the treatment-naïve PNV patients who were scheduled to undergo combination therapy between September 2017 and November 2018. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as loading doses. Full-dose PDT was performed within 1 week of the first injection. Retreatment was allowed if evidence of clinical deterioration or the presence of fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Changes in the central foveal thickness (CFT), central choroidal thickness (CCT), and retreatment rate during the maintenance phase were also evaluated. RESULTS: Eleven eyes were enrolled in this study. Significantly, better BCVA was observed at 12 months than at baseline (P = 0.010). The mean CFT significantly decreased from 331 ± 93 to 237 ± 72 µm at 12 months (P < 0.001). The mean CCT also significantly decreased from 361 ± 74 to 310 ± 83 µm at 12 months (P < 0.001). The mean number of injections per eye was 3.9 ± 1.3 during the follow-up period. A total of 45.5% (5 /11) of the patients required retreatment during the maintenance phase. CONCLUSION: Anti-VEGF combined with full-dose PDT was well tolerated and appeared to be effective treatment for patients with treatment-naïve PNV. Combination therapy might also reduce the treatment burden with fewer injections in patients with PNV.

Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). METHODS: We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. RESULTS: BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. CONCLUSION: A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV.

Detailed in vitro study of the photosensitization reaction of extracellular Talaporfin sodium in rat myocardial cells.

BACKGROUND AND OBJECTIVE: We proposed a new non-thermal treatment for tachyarrhythmia that employs an extracellular photosensitization reaction. Oxygen depletion may easily occur in in vitro studies of this reaction because the photosensitizing agent is often highly concentrated in such studies. The aim of the current study was to examine the progress of the extracellular photosensitization reaction and the photocytotoxicity of extracellular Talaporfin sodium on myocardial cells for application in tachyarrhythmia therapy. MATERIALS AND METHODS: Photosensitization reactions were performed in single wells of 96-well plates; Talaporfin sodium solution concentrations from 5 to 40 µg/ml, radiant exposures up to 40 J/cm(2) , and irradiance of 0.29 W/cm(2) from a continuous wave (CW) red diode laser (wavelength: 663 nm) were used. We measured transient changes of temperature, photosensitizer fluorescence, dissolved oxygen pressure, and photosensitizer solution absorbance to monitor the progress of the photosensitization reaction in the system during laser irradiation. Rat myocardial cells were cultured in 96-well plates, and the drug-light interval was set to 15 minutes. We used a WST assay to measure cell lethality 2 hours after laser irradiation. RESULTS: A strong photosensitization reaction occurred several seconds after initiation of laser irradiation; this initial reaction depended upon dissolved oxygen. A gentler continuous photosensitization reaction followed the initial reaction, and was associated with temperature increases of less than 10°C. The oxygen pressure was kept in approximately 40 mmHg of the myocardial tissue oxygen pressure in the gentle photosensitization reaction phase. At radiant exposures from 10 to 40 J/cm(2) , a photosensitizer concentration of approximately 15 µg/ml was the threshold for myocardial cell necrosis in this in vitro system. The dependencies of photocytotoxicity on radiant exposure were separated into two distinct groups based on the molecular density ratio between Talaporfin sodium and albumin. CONCLUSIONS: This in vitro system for the extracellular photosensitization reaction may reflect the situation in live myocardial tissue. We found that the extracellular photosensitization reaction progressed in two distinctive phases; the first phase depended upon dissolved oxygen, and the second upon the molar density ratio between Talaporfin sodium and albumin. Cell lethality due to the extracellular photosensitization reaction was influenced by both of these factors in our in vitro system. We suggest that a photosensitizer concentration of 25 µg/ml might be necessary to treat myocardial tissue with therapies involving the extracellular photosensitization reaction.

A Case of Group A Streptococcus Bacteremia and Infective Endocarditis Caused by Right Ovarian Tube Endometriosis Where the Patient's Perspective Was Key to the Diagnostic Process.

Group A streptococcus pyogenes (GAS) is a common organism that can cause upper respiratory infections. We encountered a case where GAS caused infective endocarditis (IE) due to an entry from the vagina. In this case, although echocardiography was negative, we were able to make a diagnosis of IE based on the 2023 Duke International Society for Cardiovascular Infectious Diseases Criteria, and we started antimicrobial therapy for IE. However, the patient subsequently developed persistent abdominal pain, which was atypical; hence, we reviewed the differential diagnosis. It is difficult to locate the primary site of infection because GAS rarely causes vaginal infections, and vaginal infections rarely cause IE. This case highlights the significance of revisiting medical history and the value of using a system 3 approach to refine diagnostic directions.

Study of blood charring precursor states using backscattering at 663 nm from blood and optical window boundary.

BACKGROUND AND OBJECTIVE: Contact laser irradiation is generally used in therapeutic laser procedures such as plastic surgery and laser catheter lead removal. However, it may induce blood charring on the surface of the optical window in blood circumstance so that the laser beam might be blocked. Various charring detection methods have been proposed, but they detect charring only after charring has occurred. This study investigates the transient behavior of red blood cells (RBCs) prior to the charring on the surface of an optical window during red laser irradiation in blood circumstance. MATERIALS AND METHODS: The backscattering light power was continuously measured to investigate the transient behavior of a 1-mm-thick porcine blood model (hematocrit: 40%) during continuous laser irradiation (center wavelength: 663 nm; irradiance: 81 W/cm(2)). A rabbit blood model was microscopically observed after irradiation. The absorption coefficient (µ(a)) and the reduced scattering coefficient (µ'(s)) were measured using a double integrating sphere setup and the inverse adding-doubling method. The backscattering light power was continuously measured in vivo during contact laser irradiation via a laser catheter in a porcine heart cavity. RESULTS: The results reveal that it may be possible to detect a precursory state of charring from a time course of the backscattering light power. µ(a) increased monotonically by 15% until charring occurred. µ'(s) decreased by 10% followed a broad peak until charring occurred. These changes in the optical property correspond to changes in the morphology of RBCs. Changes in the backscattering light power measured in vivo were similar to those measured ex vivo. CONCLUSIONS: The transient optical changes in blood prior to charring may be caused by changes in the morphology of RBCs on the optical window surface. Backscattering light power measurements may be a practical method to detect the precursor state of charring.

Rare presentation of emphysematous pyelonephritis due to faulty catheter insertion.

Emphysematous pyelonephritis is a severe necrotizing infection that occurs predominately among individuals with diabetes mellitus. The mortality rate is >10% only medical therapy. We report a case of emphysematous pyelonephritis caused by Klebsiella pneumoniae, precipitated by faulty catheter insertion. The patient recovered after the replacement of catheter and administration of antibiotics.

Short-term outcomes of switching to brolucizumab in japanese patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the outcomes of a 6-month follow-up after switching to brolucizumab from aflibercept to treat neovascular age-related macular degeneration (AMD) in Japanese patients. STUDY DESIGN: Retrospective observational study. METHODS: We studied 45 consecutive eyes of 42 patients diagnosed with neovascular AMD, who were switched to intravitreal brolucizumab injection (IVBr) after receiving intravitreal aflibercept injection (IVA) using a treat-and-extend (TAE) regimen. Patients who had brolucizumab-associated intraocular inflammation (IOI) were excluded from the study. The mean changes in the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness (CCT), and treatment intervals were evaluated at 6 months after the switch to IVBr. RESULTS: One eye of 1 patient was excluded because of IOI after the switch; 44 eyes of 41 patients were enrolled in this study. The mean logMAR BCVA was maintained throughout the follow-up period when compared with the baseline value (P > .05 at 6 months). However, the mean CFT and CCT at 6 months had decreased significantly (P < .05 and P < .001, respectively). The mean treatment interval was extended from 5.75 to 8.12 weeks. CONCLUSION: Switching to brolucizumab from aflibercept using a TAE regimen might be effective for maintaining functional outcomes and extending intervals in Japanese patients with AMD.

One-year outcomes of intravitreal brolucizumab injections in patients with polypoidal choroidal vasculopathy.

To evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.

Endophthalmitis outbreak caused by Fusarium oxysporum after cataract surgery.

PURPOSE: To evaluate an outbreak of endophthalmitis caused by Fusarium oxysporum after cataract surgery. METHODS: In the present study, we conducted a retrospective review of the medical records of cases of endophthalmitis that developed after cataract surgery. All eyes underwent phacoemulsification and intraocular lens implantation (PEA + IOL) at a single eye clinic on the same date. Symptoms of endophthalmitis occurred 21.5 ± 3.4 days after the cataract surgery. RESULTS: Nine eyes of 9 patients with fungal endophthalmitis (5 males and 4 females) were enrolled in the current study. The mean age of the patients was 63.4 ± 8.5 years. Soon after the diagnosis of endophthalmitis, pars plana vitrectomy (PPV) had been performed in all the eyes. However, because there was no response to the first PPV plus antibacterial drug therapy, we performed repeat PPV for all the eyes, combined with IOL removal and antifungal therapy (natamycin eye drops plus oral voriconazole or fosfluconazole). After the antifungal drug therapy, no recurrence of endophthalmitis was observed in any of the operated eyes, and good visual outcomes were obtained. Fusarium oxysporum was identified by culture and sequencing analysis. CONCLUSION: Early diagnosis and appropriate, adequate treatment are needed for successful management of fungal endophthalmitis.

Myocardial electrical conduction block induced by photosensitization reaction in exposed porcine hearts in vivo.

BACKGROUND AND OBJECTIVE: This study proposes photosensitization reaction for non-thermal cardiac ablation in arrhythmia therapy. Acute and chronic phase experiments were conducted in exposed porcine hearts to demonstrate the photosensitization reaction-induced myocardial electrical conduction block in vivo. STUDY DESIGN/MATERIALS AND METHODS: The porcine left atrial appendage was exposed under an open-chest procedure. Then, a water-soluble chlorin photosensitizer, NPe6, was injected into the pigs intravenously at 5 or 10 mg/kg. About 15 or 30 minutes after the injection, a 663-nm continuous-wave diode laser was irradiated on the surface of the atrial appendage through a silica optical fiber. The laser energy was delivered to the tissue point by point at an energy density of 50-208 J/cm(2). RESULTS: Acute and chronic tissue damages as a result of the photosensitization reaction were determined by electrophysiology and histology, respectively. The change in the myocardial conduction time between two electrodes was measured immediately after the completion of the 35-mm irradiation line between the electrodes. The conduction delay of 35.5 milliseconds might be due to the change in the conduction pathway induced by transmural acute conduction block with the photosensitization reaction. The tissue temperature increase in the irradiated area was approximately 12.8°C. Azan-staining revealed about 1-mm transmural fibrosis of the atrial appendage at 2 weeks after the irradiation (50 J/cm(2)). CONCLUSIONS: The results suggest that the photosensitization reaction might induce acute and chronic myocardial electrical conduction block. Cardiac ablation with the photosensitization reaction might be a non-temperature-mediated methodology for arrhythmia therapy.

Incidence of elevated intraocular pressure after intravitreal injection in Japanese patients with age-related macular degeneration.

The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.

The effect of simulated gestational weight gain on balance, gait, and fear of falling.

The effects of pregnancy on balance with the eyes closed and maximum walking speed remain unclarified. The present study aimed to examine the effect of simulated gestational weight gain on balance, gait, and fear of falling in nulligravid women to enhance understanding of the impact of gestational weight gain. We prospectively evaluated the following outcomes in 24 healthy nulligravid women with and without a maternity-simulation jacket that simulated third-trimester pregnancy. To measure balance, we used the single-leg-stance test with eyes open and closed, and the functional reach test. We evaluated gait function by measuring walking speed, step length, and cadence at self-selected and maximum speeds. We used the timed-up-and-go test as a comprehensive measure of gait and balance, and the modified falls efficacy scale to evaluate fear of falling. Differences in these parameters between a simulated gestational weight gain condition and a "nonpregnant" condition were assessed. Simulated gestational weight gain caused significantly worse performances in the single-leg-stance test with eyes open and closed, functional reach test, walking speed, step length at self-selected and maximum speeds, and timed-up-and-go test. The effect size was larger for the single-leg-stance test with eyes closed than with eyes open. The average score for each modified falls efficacy scale item ranged from 4.7-8.5. In conclusion, balance decreased with simulated gestational weight gain, and balance may be more affected without visual feedback. Simulated gestational weight gain resulted in worse gait function at both self-selected and maximum speeds.

Fake metabolomics chromatogram generation for facilitating deep learning of peak-picking neural networks.

Finding peaks in chromatograms and determining their start and end points (peak picking) is a core task in chromatography based biotechnology. Construction of peak-picking neural networks by deep learning was, however, hampered from the preparation of exact peak-picked or "labeled" chromatograms since the exact start and end points were often unclear in overlapping peaks in real chromatograms. We present a design of a fake chromatogram generator, along with a method for deep learning of peak-picking neural networks. Fake chromatograms were generated by generation of fake peaks, random sampling of peak positions from feature distributions, and merging with real blank sample chromatograms. Information on the exact start and end points, as labeled on the fake chromatograms, were effective for training and evaluating peak-picking neural networks. The peak-picking neural networks constructed herein outperformed conventional peak-picking software and showed comparable performance with that of experienced operators for processing the widely targeted metabolome data. Results of this study indicate that generation of fake chromatograms would be crucial for developing peak-picking neural networks and a key technology for further improvement of peak picking neural networks.

Correlation between choroidal structure and smoking in eyes with central serous chorioretinopathy.

PURPOSE: A smoking habit can cause various health problems encompassing retinal diseases including central serous chorioretinopathy (CSC). The aim of the current study was to investigate the effect of smoking on the choroidal structure in patients with CSC. METHODS: The choroidal vascular index (CVI) was calculated using the binarized OCT images. Baseline parameters (age, refractive error [SE], subfoveal choroidal thickness [SFCT] and CVI) were compared between smokers and non-smokers using Wilcoxon rank sum test. Moreover, the associations between SFCT and the baseline parameters were analyzed using a multivariate linear regression followed by the AICc model selection. RESULTS: Among 75 CSC patients, 45 patients were smokers and 30 patients were non-smokers. No significant differences in age and SE were seen between the smoking group and the non-smoking group. A significant difference in the SFCT was seen between two groups (382.0 ± 68.2 µm in the smoking group vs. 339.3 ± 52.3 µm in the non-smoking group, p = 0.0038), while no significant difference was observed in the CVI (p = 0.32). The optimal model for SFCT included the variables of age, SE and past history of smoking among the baseline parameters. Additionally, increased pack years was associated with increased SFCT. CONCLUSION: Cigarette smoking was associated with an increased SFCT in patients with CSC. Thicker choroid in smoking CSC patients may be an important modulator of the disease.

Comparison of one-year results of photodynamic therapy combined with ranibizumab or aflibercept for treating polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.

Sensitivity and specificity of high-resolution wide field fundus imaging for detecting neovascular age-related macular degeneration.

PURPOSE: Early detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs. METHODS: We retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard. RESULTS: Ninety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively. CONCLUSION: ClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment.

Reproducible production and image-based quality evaluation of retinal pigment epithelium sheets from human induced pluripotent stem cells.

Transplantation of retinal pigment epithelial (RPE) sheets derived from human induced pluripotent cells (hiPSC) is a promising cell therapy for RPE degeneration, such as in age-related macular degeneration. Current RPE replacement therapies, however, face major challenges. They require a tedious manual process of selecting differentiated RPE from hiPSC-derived cells, and despite wide variation in quality of RPE sheets, there exists no efficient process for distinguishing functional RPE sheets from those unsuitable for transplantation. To overcome these issues, we developed methods for the generation of RPE sheets from hiPSC, and image-based evaluation. We found that stepwise treatment with six signaling pathway inhibitors along with nicotinamide increased RPE differentiation efficiency (RPE6iN), enabling the RPE sheet generation at high purity without manual selection. Machine learning models were developed based on cellular morphological features of F-actin-labeled RPE images for predicting transepithelial electrical resistance values, an indicator of RPE sheet function. Our model was effective at identifying low-quality RPE sheets for elimination, even when using label-free images. The RPE6iN-based RPE sheet generation combined with the non-destructive image-based prediction offers a comprehensive new solution for the large-scale production of pure RPE sheets with lot-to-lot variations and should facilitate the further development of RPE replacement therapies.