Clinical characteristics and cytological changes in mucinous obstruction diagnosed by dacryoendoscopy.

To analyze the clinical characteristics of mucinous obstruction diagnosed by dacryoendoscopy and compared the cytological changes with membranous obstruction using a modified liquid-based thin prep cytology method. A retrospective chart review was conducted on 53 eyes of 51 patients with mucus obstruction based on dacryoendoscopic findings from January 2022 to October 2022. Liquid-based thin-prep cytology was performed by irrigating the inside of the nasolacrimal drainage system with saline during dacryoendoscopy-guided silicone tube intubation. Pathological findings were analyzed through a comparison of mucinous obstruction with membranous obstruction as determined by dacryoendoscopic findings. The modified liquid-based thin prep cytology technique had a higher cytology detection rate across all cases. Mucinous obstruction exhibited a significantly higher number of successful canalicular irrigation test cases compared to membranous obstruction. In mucinous obstruction, epithelial squamous cells were more frequently detected in pre-sac obstruction, whereas columnar epithelial cells were predominant in post-sac obstruction. Inflammatory cells showed a stronger correlation with primary change and post-sac obstruction. Bacterial colonies were observed exclusively in cases of mucinous obstruction. The use of a modified liquid-based thin prep cytology method enables the examination of histopathological changes in the lacrimal passage in primary acquired nasolacrimal duct obstruction (PANDO), particularly in cases of mucinous obstruction, without the need for invasive biopsies. These findings enhance the understanding of the etiopathogenesis of mucinous obstruction, complementing knowledge of membranous obstruction in PANDO.

One year monitoring of retinal morphologic and functional changes in traumatic optic neuropathy patients.

BACKGROUND: To analyze the morphologic and functional change in traumatic optic neuropathy (TON) divided by the mechanism of optic nerve injury. METHODS: A retrospective analysis of 58 patients who were diagnosed as monocular TON from February 2015 to August 2021 was conducted at in CHA Bundang Medical Center in Seongnam, South Korea. The patients visited the clinic of the department of ophthalmology for more than 6 months and at least 4 times during this period. RESULTS: 44 patients were classified as blunt TON patients, and 14 patients were surgical TON patients. The visual acuity showed significant decrease in traumatic eyes at the first visit after injury compared to fellow eyes and maintained the injured status during the 1-year follow-up period in blunt TON. In surgical TON, the visual acuity slightly improved during 1 month follow-up period. RNFL thickness tended to be decreased at 1 month after first visit blunt TON patients, which was earlier than surgical TON patients. GCIPL thickness showed earlier decreased than RNFL thickness in both blunt and surgical TON patients. CONCLUSIONS: In both blunt and surgical TON eyes, there was a notable thinning in both RNFL and GCIPL, with particularly remarkable reduction in GCIPL in early phase. Therefore, analyzing each retinal layer thickness using OCT in conjunction with assessing visual function would be necessary. This combined approach is not only crucial for understanding clinical courses of each TON, but also predicting the morphological and functional deteriorations in TON.

A novel classification of senile dermatochalasis: insights from clinical and histological analysis.

PURPOSE: Dermatochalasis is a common disorder of the elderly, often requiring upper blepharoplasty. Although it is mainly accepted as a process of aging, its clinical and histological findings vary among patients. The aim of this study was to classify types of dermatochalasis based on their clinical and histological findings. METHODS: This retrospective study included patients with dermatochalasis who had undergone senile blepharoplasty at a single center. Clinical parameters such as margin-to-reflex distance 1 (MRD1), eyelid contour, visual field, and pre-existing medical conditions were assessed. Histological analysis was conducted of eyelid tissues stained with hematoxylin and eosin (H&E) and D2-40 to evaluate dermal edema, inflammation, lymphatic changes, and stromal depth. RESULTS: This study included 67 eyes of 35 patients. The mean age of the patients was 69.0 ± 8.3 years, and the average MRD1 was 1.8 ± 1.3 mm. In correlation analysis, two distinct types of dermatochalasis based on the histological findings were identified: lymphangiectasia-dominant and stromal edema-dominant types. The difference between nasal and temporal side MRD1(NT-MRD1) showed the area under the ROC curve of 0.718 of for distinguishing the two histological types of dermatochalasis was 0.718. CONCLUSION: Our novel classification of senile dermatochalasis based on morphological and histological analysis provides insights into the underlying pathology and may help to predict surgical outcomes and complications.

Sensory Function of Children With Strabismus After Epiblepharon Surgery.

PURPOSE: To investigate the effect of epiblepharon surgery on motor and sensory function in children with epiblepharon and concomitant strabismus. METHODS: Among 564 patients who underwent epiblepharon correction surgery from May 2016 to April 2023, 45 children who were examined for strabismus were included in the study. Preoperative and postoperative visual acuity, refraction, and angle of deviation were analyzed. For those with significant angle of deviation, additional stereopsis, sensory fusion, and returning time were retrospectively investigated. The angle of deviation was examined by one examiner at distance and near. RESULTS: The mean age of 45 children (18 boys and 27 girls) was 6.8 ± 2.9 years. Fifteen had significant strabismus at the time of epiblepharon surgery. Visual acuity improved in both the total and strabismus groups. Improvement in stereopsis and fusion was also observed in the strabismus group. The angle of deviation showed no difference in both groups. CONCLUSIONS: Epiblepharon could affect ocular manifestations of strabismus as shown in this study. The authors suggest strabismus treatment be continued after epiblepharon surgery, with improved sensory function. Further evaluation with larger groups is needed in the future. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Comparison of Outcomes of Silicone Tube Intubation with or without Dacryoendoscopy for the Treatment of Congenital Nasolacrimal Duct Obstruction.

In this retrospective study, we compared and analyzed two groups of patients who underwent silicone tube intubation (STI) to treat congenital nasolacrimal duct obstruction (CNDO). We employed dacryoendoscopy to visualize the lacrimal pathways of one group. In total, 85 eyes of 69 patients were included (52 of 41 patients in the non-dacryoendoscopy and 33 eyes of 28 patients in the dacryoendoscopy group). Clinical characteristics, dacryoendoscopic findings, and surgical outcomes were evaluated. The overall STI success rate was 91.8%, and the success rate was significantly higher in the dacryoendoscopy versus non-dacryoendoscopy group (97.0% and 88.5%, respectively). For patients < 36 months of age, the success rate was 100% (23 eyes). All patients with Hasner valve membranous obstructions were younger than 36 months and had structural obstructions of the lacrimal drainage system (LDS) (p = 0.04). However, in patients lacking Hasner valve obstructions, LDS secretory (50.0%) and structural (50%) obstructions occurred at similar rates, which did not vary by age. Dacryoendoscopy-assisted STI enhanced the therapeutic efficacy of CNDO and identified diverse CNDO etiologies beyond Hasner valve obstructions. These findings emphasize the potential advantages of dacryoendoscopy in surgical treatment for CNDO patients.

Unveiling Neuroprotection and Regeneration Mechanisms in Optic Nerve Injury: Insight from Neural Progenitor Cell Therapy with Focus on Vps35 and Syntaxin12.

Axonal degeneration resulting from optic nerve damage can lead to the progressive death of retinal ganglion cells (RGCs), culminating in irreversible vision loss. We contrasted two methods for inducing optic nerve damage: optic nerve compression (ONCo) and optic nerve crush (ONCr). These were assessed for their respective merits in simulating traumatic optic neuropathies and neurodegeneration. We also administered neural progenitor cells (NPCs) into the subtenon space to validate their potential in mitigating optic nerve damage. Our findings indicate that both ONCo and ONCr successfully induced optic nerve damage, as shown by increases in ischemia and expression of genes linked to neuronal regeneration. Post NPC injection, recovery in the expression of neuronal regeneration-related genes was more pronounced in the ONCo model than in the ONCr model, while inflammation-related gene expression saw a better recovery in ONCr. In addition, the proteomic analysis of R28 cells in hypoxic conditions identified Vps35 and Syntaxin12 genes. Vps35 preserved the mitochondrial function in ONCo, while Syntaxin12 appeared to restrain inflammation via the Wnt/ß-catenin signaling pathway in ONCr. NPCs managed to restore damaged RGCs by elevating neuroprotection factors and controlling inflammation through mitochondrial homeostasis and Wnt/ß-catenin signaling in hypoxia-injured R28 cells and in both animal models. Our results suggest that ischemic injury and crush injury cause optic nerve damage via different mechanisms, which can be effectively simulated using ONCo and ONCr, respectively. Moreover, cell-based therapies such as NPCs may offer promising avenues for treating various optic neuropathies, including ischemic and crush injuries.

Recovery of the Ratio of Closure Time during Blink Time in Lacrimal Passage Intubation.

(1) Background: We aim to find a novel blink parameter in nasolacrimal duct obstruction (NDO) patients and analyze parameters that could reflect subjective symptoms and objective indicators at the same time through a blink dynamic analysis. (2) Methods A retrospective study was conducted with 34 patients (48 eyes) who underwent lacrimal passage intubation (LPI) and 24 control groups (48 eyes). All patients' blink patterns were measured using an ocular surface interferometer before and after LPI, including total blink (TB) and partial blink (PB) and the blink indices blink time (BT), lid closing time (LCT), closure time (CT), lid opening time (LOT), interblink time (IBT), closing speed (CS) and opening speed (OS). The tear meniscus height (TMH) was measured, and the questionnaire "Epiphora Patient's Quality of Life (E-QOL)," which includes daily activity restriction as well as static and dynamic activities, was completed. (3) Results: Compared to CT and the ratio of CT during BT (CT/BT) in control (89.4 ± 20.0 msec, 13.16%), those in NDOs were longer (140.3 ± 92.0 msec, 20.20%) and were also related to TMH. After LPI, CT and CT/BT were recovered to 85.4 ± 22.07 msec, 13.29% (p < 0.001). CT and CT/BT showed a positive correlation with the E-QOL questionnaire score, particularly with dynamic activities. (4) Conclusions: CT and CT/BT, which are objective indicators associated with subjective symptoms of patients, are considered new blink indices for the evaluation of NDO patients with Munk's score.

Application of an Interpretable Machine Learning for Estimating Severity of Graves' Orbitopathy Based on Initial Finding.

(1) Background: We constructed scores for moderate-to-severe and muscle-predominant types of Graves' orbitopathy (GO) risk prediction based on initial ophthalmic findings. (2) Methods: 400 patients diagnosed with GO and followed up at both endocrinology and ophthalmology clinics with at least 6 months of follow-up. The Score for Moderate-to-Severe type of GO risk Prediction (SMSGOP) and the Score for Muscle-predominant type of GO risk Prediction (SMGOP) were constructed using the machine learning-based automatic clinical score generation algorithm. (3) Results: 55.3% were classified as mild type and 44.8% were classified as moderate-to-severe type. In the moderate-to-severe type group, 32.3% and 12.5% were classified as fat-predominant and muscle-predominant type, respectively. SMSGOP included age, central diplopia, thyroid stimulating immunoglobulin, modified NOSPECS classification, clinical activity score and ratio of the inferior rectus muscle cross-sectional area to total orbit in initial examination. SMGOP included age, central diplopia, amount of eye deviation, serum FT4 level and the interval between diagnosis of GD and GO in initial examination. Scores ≥46 and ≥49 had predictive value, respectively. (4) Conclusions: This is the first study to analyze factors in initial findings that can predict the severity of GO and to construct scores for risk prediction for Korean. We set the predictive scores using initial findings.

Clinical Implication of Dacryoendoscopy in the Patients with Tearing: A Systematic Review.

PURPOSE: A systematic review of the literature on diagnostic and therapeutic indications, techniques, and complications of dacryoendoscopy (DE) was performed. METHODS: The authors performed a PubMed search of articles published in English on DE. Data were collected and classified according to the categories of the disease. The clinical outcomes and limitations were particularly analyzed. RESULTS: The lacrimal drainage system from the canaliculus to the inferior meatus could be examined based on the specific anatomical features by DE. The canalicular mucosa is smooth and brightly colored, the lacrimal sac shows covering mucosa with good vascularization and the nasolacrimal duct is lined with bright tubular mucosal folds. DE allows direct visualization of the detailed internal condition of the lacrimal disorders, to directly diagnose the site of obstruction with accuracy and address the causes and recanalize the lacrimal drainage system using assisted micro lacrimal surgical instruments in the tearing patients. CONCLUSIONS: Better visualization of the lacrimal canal with DE improves the understanding of physiology and precise identification of the obstructing lesions, both of which are the key to a comprehensive management for the tearing patients.

The technique and its role of dacryoendoscopy in the management of the false passage of the lacrimal drainage system.

This is a retrospective study of patients with primary acquired nasolacrimal duct obstruction (PANDO) who underwent dacryoendoscopy (FT-203F; Fibertech Co., Tokyo, Japan) and sheath-guided silicone intubation for 830 cases with PANDO from March 2016 to December 2020. 19 cases (2.3%) were observed as false passage in the lacrimal drainage system (LDS). Dacryoendoscopic findings revealed that the following factors were associated with LDS obstruction (% cases): structural change of 63.2% (stenosis, 42.1%; fibrotic membrane, 21.1%), and secretory change of 36.8% (mucus, 15.8%; stone, 10.5%; and granulation, 10.5%). The obstruction sites were distributed through LDS. The false passages detected in LDS were managed as follow: usage of fluid irrigation pressure to check the true passage following the previously intubated silicone tube as a reference, and confirmation the end of passage through the inferior meatus with nasal endoscopy. The overall success rate was 73.7% using this management technique. Dacryoendoscopy enables real-time observation of the lumen of the LDS, thus facilitating management of pathological lesions including false passages. With this technique, we are better able to make customized treatment of patients with false passages, with a safer and more effective results leading to the success of dacryoendoscopy guided silicone tube intubation in PANDO patients.

The Role of Extracellular Vesicles in Optic Nerve Injury: Neuroprotection and Mitochondrial Homeostasis.

Stem cell therapies hold great promise as alternative treatments for incurable optic nerve disorders. Although mesenchymal stem cells exhibit various tissue regeneration and recovery capabilities that may serve as valuable therapies, the clinical applications remain limited. Thus, we investigated the utility of extracellular vesicles (EVs) from human placenta-derived mesenchymal stem cells (hPSCs) in this context. Hypoxically preconditioned hPSCs (HPPSCs) were prepared via short-term incubation under 2.2% O2 and 5.5% CO2. The EVs were then isolated. R28 cells (retinal precursor cells) were exposed to CoCl2 and treated with EVs for 24 h. Cell proliferation and regeneration were measured using a BrdU assay and immunoblotting; ATP quantification revealed the extent of the mitochondrial function. The proteome was determined via liquid chromatography-tandem mass spectroscopy. Differentially expressed proteins (DEPs) were detected and their interactions identified. HPPSC_EVs functions were explored using animal models of optic nerve compression. HPPSC_EVs restored cell proliferation and mitochondrial quality control in R28 cells damaged by CoCl2. We identified DEPs (p < 0.05) that aided recovery. The mitochondrial DEPs included LONP1; PARK7; VDAC1, 2, and 3; HSPD1; and HSPA9. EVs regulated the levels of mitophagic proteins in R28 cells injured by hypoxia; the protein levels did not increase in LONP1 knockdown cells. LONP1 is a key mediator of the mitophagy that restores mitochondrial function after hypoxia-induced optic nerve injury.

Dacryoendoscopic Findings in the Failed Silicone Tube Intubations without Dacryoendoscopy.

PURPOSE: To investigate the clinical characteristics and dacryoendoscopic findings and clinical efficacy of silicone tube intubation (STI) in the patients who referred to our center due to failed with conventional STI. METHODS: We retrospectively reviewed the medical records of 61 cases from 50 patients who underwent STI or endoscopic dacryocystorhinostomy using dacryoendoscopy from January 2016 to May 2021. Clinical characteristics, tear meniscus height, lacrimal irrigation test, dacryocystographic findings, dacryoendoscopic findings and surgical outcomes were evaluated. RESULTS: The study included 12 male and 38 female patients (mean age, 64.1 ± 13.2 years). In the preoperative lacrimal irrigation test, passage was found in 33 eyes (54.1%) and no passage in 28 eyes (45.9%). The causes of lacrimal duct obstruction were in the order of stenosis (31.1%), mucus (27.9%), membrane (24.6%), granulation (13.1%), and stone (3.3%), and the location were in the order of nasolacrimal duct (39.3%), lacrimal sac (36.1%), canaliculus (21.3%), and inferior meatus (3.3%). As for the characteristics of obstruction, the secretory type was 21 eyes (34.4%), and structural change type was 40 eyes (65.6%). The STI group consisted of 57 eyes (93.4%) and endoscopic dacryocystorhinostomy consisted of four eyes (6.6%). The overall success rate was 83.9%. Clinical results were correlated with dacryoendoscopic finding (p = 0.015), but not with lacrimal irrigation test or dacryocystography. The structural change type had a higher surgical success rate than the secretory type (84.4% vs. 66.7%, p = 0.015). In particular, the structural change type showed higher success rate than the secretory type below the lacrimal sac (95.5% vs. 61.9%, p = 0.034). CONCLUSIONS: STI using dacryoendoscopy has a higher surgical success rate than conventional STI since dacryoendoscopy provides direct visualization of nasolacrimal duct obstruction. It could be useful in increasing the surgical success rate in patients with structural changes below lacrimal sac.

Dacryoendoscopic Findings of Patients with Lacrimal Drainage Obstruction Associated with Cancer Treatment.

PURPOSE: To compare the diagnosis and treatment outcome of lacrimal drainage obstruction of patients who underwent systemic chemotherapy (CTx) or radioactive iodine treatment (RAI) by using dacryoendoscopy and at the same time performing dacryoendoscopy-guided silicone tube insertion (STI) to treat epiphora. METHODS: From July 2017 to December 2020, the medical records of 11 patients (16 eyes) were diagnosed with lacrimal drainage obstruction after CTx or RAI and underwent dacryoendoscopy-guided STI were reviewed retrospectively. We tried to count the number of obstructive sites in total patients using slit-lamp examination and dacryoendoscopic findings. RESULTS: A total of 11 patients, 16 eyes, were enrolled in this study. The onset of epiphora in the CTx group (3.0 ± 4.0 months) was significantly shorter than that in the RAI group (52.6 ± 36.5 months, p = 0.001). There were total 32 obstructive sites including 28 obstructive sites of dacryoendoscopic findings and four sites of punctual stenosis in total 16 cases. Using dacryoendoscopy, granulation findings was dominant in RAI patients (p = 0.038) and mucus finding was frequent mostly in lacrimal sac and canaliculus. In the CTx group, mucosal edema finding was dominant (p = 0.038) and fibrotic membrane finding was frequent in all levels of lacrimal drainage system. Regarding the obstructive location, lacrimal sac was the most frequently obstructed site in the two groups (p = 0.038). CONCLUSIONS: The onset of epiphora in the CTx group was significantly earlier than in the RAI group. In the CTx group, mucosal edema finding was frequent in all levels of lacrimal drainage system. In the RAI group, granulation finding was frequent mostly in lacrimal sac and canaliculus. Since the clinical outcome was satisfactory, intervention with dacryoendoscopy-guided STI could be a treatment of choice in patients with epiphora after CTx or RAI.

TGFß-Treated Placenta-Derived Mesenchymal Stem Cells Selectively Promote Anti-Adipogenesis in Thyroid-Associated Ophthalmopathy.

Orbital fibroblasts (OFs) in thyroid-associated ophthalmopathy (TAO) are differentiated from pre-adipocytes and mature adipocytes; increased lipid and fat expansion are the major characteristics of ophthalmic manifestations. Human placental mesenchymal stem cells (hPMSCs) were reported to immunomodulate pathogenesis and suppress adipogenesis in TAO OFs. Here, we prepared transforming growth factor ß (TGFß, 20 ng/mL)-treated hPMSCs (TGFß-hPMSCs) in order to enhance anti-adipogenic effects in vitro and in TAO mice. TAO OFs were grown in a differentiation medium and then co-cultured with hPMSCs or TGFß-hPMSCs. TAO OFs were analyzed via quantitative real-time polymerase chain reaction, Oil red O staining, and western blotting. The results showed that TGFß-hPMSCs reduced the expression of adipogenic, lipogenic, and fibrotic genes better than hPMSCs in TAO OFs. Moreover, the adipose area decreased more in TAO mice injected with TGFß-hPMSCs compared to those injected with hPMSCs or a steroid. Further, TGFß-hPMSCs inhibited inflammation as effectively as a steroid. In conclusion, TGFß-hPMSCs suppressed adipogenesis and lipogenesis in vitro and in TAO mice, and the effects were mediated by the SMAD 2/3 pathways. Furthermore, TGFß-hPMSCs exhibited anti-inflammatory and anti-fibrotic functions, which suggests that they could be a new and safe method to promote the anti-adipogenic function of hPMSCs to treat TAO patients.

Liquid-based thin-prep cytology study of lacrimal drainage system in primary acquired nasolacrimal duct obstruction.

PURPOSE: We investigated the cytologic findings of primary acquired nasolacrimal duct obstruction (PANDO) based on the thin-prep cytology method using sheath-guided dacryoendoscopy. METHODS: A retrospective review was conducted of 66 cases from 50 patients who were diagnosed with PANDO. Slit-lamp examination, the lacrimal irrigation test, and dacryocystography were performed for the evaluation of PANDO. The dacryocystography (DCG) findings were classified into primary and secondary change. Each patient was treated with transcanalicular dacryoplasty using catheter sheath-guided dacryoendoscopy (RUIDO Fiberscope, Fiber Tech Co., Ltd., Tokyo, Japan) and obtained cytologic specimens. The liquid-based thin-prep cytology method was used for the analysis of histopathology. RESULTS: The cellular detection rate was as follows: epithelial cells with 56 cases (84.8%), 33 cases (50.0%) with inflammatory cells, 1 case (1.5%) with mucin, and bacterial colonies with 2 cases (3.0%). In the dacryoendoscopic findings, all cases of a presence of pus were related to the detection of the columnar epithelium (p = 0.026), while there was no statical significance according to the presence of an epithelial cell. In the DCG findings, the PANDOs with the secondary change showed a higher detection rate than those with the primary change (p = 0.005), and columnar epithelial cells were observed (p = 0.011). The detection rate of inflammatory cells was 50.0% (33/66) and all inflammatory cells were lymphocytes but it was not correlated with clinical findings. One case of mucin (1.5%) and 2 cases of bacterial colonies (3.0%) were presented using liquid-based thin-prep cytology analysis. The overall success rate of transcanalicular dacryoplasty and silicone intubation was 86.4%. CONCLUSION: Liquid based thin prep cytology can be used to analyze histopathological changes of lacrimal passage in PANDO without invasive biopsy. These cytologic findings of lacrimal passage provide a better understanding of the pathogenesis of lacrimal passage in patients with PANDO.

A nationwide cohort study on the risk of ADHD in children with amblyopia mediated by fine motor skill impairment in East Asia.

This national administrative investigation of Republic of Korea compared the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders(ASD) in preschool amblyopic children and identified factors that possibly mediate this association. After propensity score (PS) matching, 7762 amblyopic children and 31,030 non-amblyopic children were included. Amblyopia was associated with ADHD (aOR:1.687; 95% CI 1.444, 1.970) but not with ASD (aOR: 0.591; 95% CI 0.341, 1.026). Fine motor skill impairment was a mediating factor in association of amblyopia with ADHD, accounting for 4.2% (95% CI 1.7, 8.0). In conclusion, amblyopic children have a greater risk of ADHD, and deficits in fine motor skills mediate this association. We suggest increased attention given to fine motor skill underdevelopment in amblyopic children to prevent the development of ADHD.

Binocular Visual Rehabilitation in Paralytic Strabismus by Botulinum A Toxin Chemodenervation.

PURPOSE: To investigate the effect of botulinum A toxin (BTXA) chemodenervation in paralytic strabismus patients without surgical correction. METHODS: A retrospective chart review of 51 patients who were diagnosed as paralytic strabismus and underwent BTXA chemodenervation was performed. The patients were divided into four groups according to the cause of paralytic strabismus of vasculopathy, neoplasm, trauma, and idiopathic. They were also divided into two groups of early and late treatment according to the initiation time of BTXA chemodenervation after the onset of strabismus (3 months), and of the initial strabismus type of exotropia and esotropia. We investigated the changes of angle of deviation and diplopia after BTXA chemodenervation. RESULTS: The average deviation of angles decreased by 25.2 prism diopter (PD) (35.1 to 9.9 PD) in total patients, and the overall success rate was 64.7% (33 by 51), and the there was no statistically significant difference in success rate between each group divided by the cause of paralytic strabismus. According to the treatment timing, the deviation of the angle decreased by 28.0 PD (36.8 to 8.8 PD) in the early treatment group, and 21.3 PD (33.5 to 12.2 PD) in late treatment group at the time of the last postinjective follow-up. According to the initial strabismus type, the average angle of deviation decreased by 20.3 PD (35.6 to 15.3 PD) in exotropia group by cranial nerve 3 palsy, and 24.4 PD (32.5 to 8.1 PD) in esotropia by cranial nerve 6 palsy. CONCLUSIONS: BTXA chemodenervation reduced the angle of deviation and the number of patients with diplopia regardless of the cause of paralytic strabismus. Early BTXA chemodenervation can be considered as the first treatment of choice in paralytic strabismus, especially in esotropia patients.

Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model.

Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 × 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-α (Tnf-α) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt/ß-catenin signaling and increased Nf-ĸb could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.

Blink index as a response predictor of blepharospasm to botulinum neurotoxin-A treatment.

PURPOSE: We investigated the blink profiles and blink index using ocular surface interferometer in the patients with blepharospasm (BSP) and identified points to consider predictive factor after BSP treatment. METHODS: In total, 117 eyelids of 59 elderly patients and 20 eyelids of 10 age-matched control group were studied. All BSP patients applied botulinum toxin-A (BoNT-A) injection for treatment of BSP. An ocular surface interferometer (LipiView; TearScience, Morrisville, NC, USA) was used to measure blink profile and blink index; total and incomplete blinks/20 s, and the partial blink ratio (PBR). Eyelid blink time (including lid closing time, closure time, lid opening time), interblink times (IBT), closing speeds (OS), and opening speeds (OS) were analyzed using 600 blinks recorded over 20 s. RESULTS: Total blink rate was significantly higher in BSP patients compared to the age-matched control group (p = .029) but other time-related and speed-related index including interpalpebral fissure, PBR, blink time, closure time (CT), interblink time, CS, and OS were not significantly different. In the responder of BSP patients, the average age was higher, CT was shorter, CS was faster than nonresponder (age; p = .016, CT; p < .001, CS; p = .042). CONCLUSION: The blink index by analyzing the blink profile using ocular surface interferometer, and this blink index may be used as a predictive factor for evaluating the clinical response after BoNT-A injection in blepharospasm patients.

PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model.

Retinal degenerative diseases result from oxidative stress and mitochondrial dysfunction, leading to the loss of visual acuity. Damaged retinal pigment epithelial (RPE) and photoreceptor cells undergo mitophagy. Pigment epithelium-derived factor (PEDF) protects from oxidative stress in RPE and improves mitochondrial functions. Overexpression of PEDF in placenta-derived mesenchymal stem cells (PD-MSCs; PD-MSCsPEDF) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCsPEDF restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H2O2)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCsPEDF augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H2O2-injured rat model, intravitreal administration of PD-MSCsPEDF restored total retinal layer thickness compared to that of naïve PD-MSCs. In particular, PTEN-induced kinase 1 (PINK1), which is the major mitophagy marker, exhibited increased expression in retinal layers and RPE cells after PD-MSCPEDF transplantation. Similarly, expression of the visual cycle enzyme retinol dehydrogenase 11 (RDH11) showed the same patterns as PINK1 levels, resulting in improved visual activity. Taken together, these findings suggest that PD-MSCsPEDF facilitate mitophagy and restore the loss of visual cycles in H2O2-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases.