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Abstract Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies.

Abstract Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called ‘personalized lag time’. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Abstract This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

This paper illustrates the improvement of needle positioning precision within corneal tissue by an automated needle insertion system utilizing a vacuum applanation pad. The system is designed to streamline the needle insertion process for deep anterior lamellar keratoplasty (DALK), where precise positioning of the needle tip is essential for successful pneumatic dissection of the diseased corneal tissue. The vacuum applanation pad of the system can fixate and flatten the corneal tissue, resulting in a fixed uniform tissue region. By penetrating the needle into the fixture region, tissue deformation - which can negatively influence needle positioning accuracy - could be minimized. Furthermore, a needle selection process regarding the gauge and length was performed to determine the optimal needle parameter with minimal end tip deflection, and a Luer lock needle fixture was designed to provide roller support that can additionally suppress deflection. Two target needle depths (400 and $500~\mu \text{m}$ ) were set to evaluate the proposed system. Ten cadaveric porcine eyes were tested for each target depth and a total of 20 data points were acquired. As a result, the system could achieve a needle end tip depth of $373.9\pm 15.9~\mu \text{m}$ (Target: $400~\mu \text{m}$ ) and $441.3\pm 22.2~\mu \text{m}$ (Target: $500~\mu \text{m}$ ), showing an overall standard deviation of $21.1~\mu \text{m}$ from the target depth. Therefore, the proposed system could achieve precise positioning of the needle within the corneal tissue to the target depth without relying on feedback information, such as that provided by real-time optical coherence tomography.

Abstract Background To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). Methods Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. Results The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (− 3.15±2.00) at 12 weeks from baseline than the placebo group (− 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. Conclusions 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Abstract Background/aims We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability. Methods We reviewed the medical records of patients aged 6–18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient’s subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near. Results Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p

Abstract Herein, a wireless and soft smart contact lens that enables real‐time quantitative recording of cholesterol in tear fluids for the monitoring of patients with hyperlipidemia using a smartphone is reported. This contact lens incorporates an electrochemical biosensor for the continuous detection of cholesterol concentrations, stretchable antenna, and integrated circuits for wireless communication, which makes a smartphone the only device required to operate this lens remotely without obstructing the wearer's vision. The hyperlipidemia rabbit model is utilized to confirm the correlation between cholesterol levels in tear fluid and blood and to confirm the feasibility of this smart contact lens for diagnostic application of cholesterol‐related diseases. Further in vivo tests with human subjects demonstrated its good biocompatibility, wearability, and reliability as a non‐invasive healthcare device.

The ischemic stroke animal model evaluates the efficacy of reperfusion and neuroprotective strategies for ischemic injuries. Various conventional methods have been reported to induce the ischemic models; however, controlling specific neurological deficits, mortality rates, and the extent of the infarction is difficult as the size of the affected region is not precisely controlled. In this paper, we report a single laser-based localized target ischemic stroke model development method by simultaneous vessel monitoring and photothrombosis induction using photoacoustic microscopy (PAM), which has minimized the infarct size at precise location with high reproducibility. The proposed method has significantly reduced the infarcted region by illuminating the precise localization. The reproducibility and validity of suggested method have been demonstrated through repeated experiments and histological analyses. These results demonstrate that our method can provide the ischemic stroke model closest to the clinical pathology for brain ischemia research from inducement, occurrence mechanisms to the recovery process.

Abstract Background This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). Methods This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. Results At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by − 6.60 for CN and − 6.63 for DQ group (all P

PurposeTo measure needle insertion force and change in intraocular pressure (IOP) in real-time during intravitreal injection (IVI). The effects of needle size, insertion speed, and injection rate to IOP change were investigated.MethodsNeedle insertion and fluid injection were performed on 90 porcine eyeballs using an automatic IVI device. The IVI conditions were divided according to needle sizes of 27-gauge (G), 30G, and 33G; insertion speeds of 1, 2, and 5 mm/s; and injection rates of 0.01, 0.02, and 0.05 mL/s. Insertion force and IOP were measured in real-time using a force sensor and a pressure transducer.ResultsThe peak IOP was observed when the needle penetrated the sclera; the average IOP elevation was 96.3, 67.1, and 59.4 mmHg for 27G, 30G, and 33G needles, respectively. An increase in insertion speed caused IOP elevation at the moment of penetration, but this effect was reduced as needle size decreased: 109.8-85.9 mmHg in 27G for 5-1 mm/s (p = 0.0149) and 61.8-60.7 mmHg in 33G for 5-1 mm/s (p = 0.8979). Injection speed was also related to IOP elevation during the stage of drug injection: 16.65 and 11.78 mmHg for injection rates of 0.05 and 0.01 mL/s (p < 0.001).ConclusionThe presented data offers an understanding of IOP changes during each step of IVI. Slow needle insertion can reduce IOP elevation when using a 27G needle. Further, the injection rate must be kept low to avoid IOP elevations during the injection stage.

Wearable electronics have been utilized for a number of applications including for ocular use, although their use has been limited to a single function. Here, the authors developed a multifunctional contact lens with wireless electronics for measurement of glucose and intraocular pressure.

The endothelialization on the poly (ε-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (ε-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (ε-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo- N -hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (ε-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (ε-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo- N -hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (ε-caprolactone) nanofibers and the maintenance of the original structure of poly (ε-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (ε-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (ε-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (ε-caprolactone) nanofiber scaffolds.

Age-related macular degeneration (AMD) is the main cause of irreversible blindness among the elderly and require early diagnosis to prevent vision loss, and careful treatment is essential. Optical coherence tomography (OCT), the most commonly used imaging method in the retinal area for the diagnosis of AMD, is usually interpreted by a clinician, and OCT can help diagnose disease on the basis of the relevant diagnostic criteria, but these judgments can be somewhat subjective. We propose an algorithm for the detection of AMD based on a weakly supervised convolutional neural network (CNN) model to support computer-aided diagnosis (CAD) system. Our main contributions are the following three things. (1) We propose a concise CNN model for OCT images, which outperforms the existing large CNN models using VGG16 and GoogLeNet architectures. (2) We propose an algorithm called Expressive Gradients (EG) that extends the existing Integrated Gradients (IG) algorithm so as to exploit not only the input-level attribution map, but also the high-level attribution maps. Due to enriched gradients, EG can highlight suspicious regions for diagnosis of AMD better than the guided-backpropagation method and IG. (3) Our method provides two visualization options: overlay and top-k bounding boxes, which would be useful for CAD. Through experimental evaluation using 10,100 clinical OCT images from AMD patients, we demonstrate that our EG algorithm outperforms the IG algorithm in terms of localization accuracy and also outperforms the existing object detection methods in terms of class accuracy.

To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests. There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0 .003. Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.

An amendment to this paper has been published and can be accessed via the original article.

Purpose. To establish an optimized and standardized protocol for the development of optimal scaffold for bioengineering corneal substitutes, we used femtosecond laser to process human corneal tissue into stromal lenticules and studied to find the most efficient decellularization method among various reagents with different tonicities. Methods. The decellularization efficacy of several agents (0.1%, 0.25%, and 0.5% of Triton X-100, SDS, and trypsin-EDTA (TE), resp.) with different tonicities was evaluated. Of all protocols, the decellularization methods, which efficiently removed nuclear materials examined as detected by immunofluorescent staining, were quantitatively tested for sample DNA and glycosaminoglycan (GAG) contents, recellularization efficacy, and biocompatibilities. Results. 0.5% SDS in hypertonic and isotonic buffer, 0.25% TE in hypotonic buffer, and 0.5% TE in all tonicities completely decellularized the corneal lenticules. Of the protocols, decellularization with hypotonic 0.25 and 0.5% TE showed the lowest DNA contents, while the GAG content was the highest. Furthermore, the recellularization efficacy of the hypotonic TE method was better than that of the SDS-based method. Hypotonic TE-treated decellularized corneal lenticules (DCLs) were sufficiently transparent and biocompatible. Conclusion. We generated an ideal protocol for DCLs using a novel method. Furthermore, it is possible to create a scaffold using a bioengineered corneal substitute.

AIM:To find the risk factors related to the reproliferation of the pterygial tissue after excision and graft surgery.METHODS:Charts of 130 eyes of 130 patients who had pterygial excision from March 2006 to April 2011 were reviewed. Preoperative pterygium morphology, surgical methods, and adjunctive treatments were statistically analyzed for their relationship with recurrence.RESULTS: During the follow-up period, recurrence was observed in 20 eyes (15.4%). None of the preoperative morphologic features were affected the rate of the recurrence. However, an age < 40y [P =0.085, odds ratio (OR) 3.609, 95% confidence interval (CI) 0.838-15.540] and amniotic membrane graft instead of conjunctival autograft (P =0.002, OR 9.093, 95% CI 2.316-35.698) were statistically significant risk factors for recurrence. Multivariate analysis revealed that intraoperative mitomycin C (MMC) (P=0.072, OR 0.298, 95% CI 0.080-1.115) decreased the rate of recurrence.CONCLUSION:Younger age is a risk factor for reproliferation of pterygial tissue after excision and amniotic membrane transplantation (AMT) are less effective in preventing recurrence of pterygium after excision based on the comparison between conjunctival autograft and AMT. Intraoperative MMC application and conjunctival autograft reduce recurrence.

Purpose. To study the correlation between ocular parameters and subjective pain that patients perceived during phacoemulsification. Methods. Medical records of 142 patients who underwent standard phacoemulsification under topical anesthesia between March and August 2016 were retrospectively reviewed. The pain during phacoemulsification and 1 h after surgery was assessed and compared using a visual analog scale. In addition, demographic data, preoperative biometric parameters, and intraoperative surgical parameters were recorded. Results. Mean age of patients was 67.49 ± 12.50 years. The mean pain score was 2.26 ± 0.85 during phacoemulsification and 0.40 ± 0.69 postoperatively. Intraoperative pain was significantly associated with higher preoperative intraocular pressure (β = 0.220, P=0.016), greater anterior chamber depth (β = 0.210, P=0.028), and greater axial length (β = 0.181, P=0.043). Conclusions. To reduce the subjective pain when patients have high preoperative intraocular pressure, large anterior chamber depth, or great axial length, supplementary procedures may be required.

Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/ mdx mice. The histopathology results showed that E-iPSC-transplanted mice exhibited enhanced muscle regeneration compared to controls. In addition, E-iPSC-derived myofibers were observed in the injured muscles. In conclusion, we show that E-iPSCs could be successfully generated from equine ADSCs and transplanted into injured muscles and that E-iPSCs have the capacity to induce regeneration of injured muscles.

Purpose. To evaluate surgical efficacy of in situ refixation technique for dislocated posterior chamber intraocular lens (PCIOL). Methods. This was a single-center retrospective case series. 34 patients (34 eyes) who underwent sclera fixation for dislocated IOLs combined with vitrectomy were studied. Of 34 eyes, 17 eyes underwent IOL exchange and the other 17 eyes underwent in situ refixation. Results. Mean follow-up period was 6 months. Mean logMAR best corrected visual acuity (BCVA) was not significantly different between the groups 6 months after surgery (0.10±0.03 in the IOL exchange group and 0.10±0.05 in the refixation group; p=0.065). Surgically induced astigmatism (SIA) was significantly lower in the refixation group (0.79±0.41) than in the IOL exchange group (1.29±0.46) (p=0.004) at 3 months, which persisted to 6 months (1.13±0.18 in the IOL exchange group and 0.74±0.11 in the refixation group; p=0.006). Postoperative complications occurred in 3 eyes in the IOL exchange group (17.6%) and 2 eyes in the refixation group (11.8%). However, all of the patients were well managed without additional surgery. Conclusion. The in situ refixation technique should be preferentially considered if surgery is indicated since it seemed to produce a sustained less SIA compared to IOL exchange.

Purpose. The purpose of this study was to evaluate the efficacy of dried human amniotic membrane (AM) in reducing the postoperative inflammatory response and scarring after strabismus surgery. Methods. The inflammatory response at the extraocular muscle reattachment site was analyzed after superior rectus (SR) resection in 12 rabbits. Dried human AM (Ambiodry2) was applied between the resected SR muscle plane and Tenon’s capsule of the left eyes of rabbits. As a control, the right eyes of rabbits underwent SR resection only. The surgeon randomly ordered which eye gets operated first during the experiment. Two weeks later, enucleation was performed. Six sagittal sections were made for each eye at the insertion of the SR muscle. The grade of postoperative inflammation and the presence of fibrosis were evaluated in histological examinations. Results. There was no statistically significant difference in the intensity of inflammation and fibrous proliferation between the eyes treated with dried human AM after SR resection and those treated with SR resection only. Conclusions. The use of dried human AM was not effective in controlling the postoperative inflammation and scarring in rabbit eyes after extraocular muscle surgery. However, this may be due to the devitalized dry preparation of human AM (Ambiodry2), which may have lost the expected anti-inflammatory and anti-scarring properties, and further studies on humans may be necessary.