Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Association Between Three Atopic Triad and Retinal Vein Occlusion Risk: A Nationwide Population-Based Study.

PURPOSE: To evaluate the association between three allergic diseases (allergic dermatitis, allergic rhinitis, and asthma) and the development of retinal vein occlusion (RVO), a major retinal disease that causes visual impairment. METHOD: This study used data obtained from the Korean National Health Insurance Claims database between 2009 and 2018. The association between the three atopic triads (allergic dermatitis, allergic rhinitis, and asthma) and the occurrence of sight-threatening RVO, as determined by diagnostic and treatment codes, were analyzed. Multivariate adjusted Cox regression analysis was used to determine the hazard ratios (HRs) and 95% confidence intervals for RVO development in the presence of allergic disease. RESULTS: In this population-based study, 2,160,195 (54.6%) individuals were male, 1,794,968 (45.4%) were female, and 620,938 (15.7%) were diagnosed with allergic diseases. Patients with either asthma or allergic rhinitis had a greater risk of RVO (adjusted hazard ratio (aHR) = 1.101, 95% confidence interval [CI] = 1.029-1.178 for asthma; aHR = 1.181, 95% CI = 1.147-1.215 for allergic rhinitis) compared to those without asthma or allergic rhinitis; however, patients with atopic dermatitis did not show a significant association with RVO (aHR = 1.071, 95% CI = 0.889-1.290), after adjusting for other risk factors. CONCLUSION: Our study revealed that allergic rhinitis, asthma, and coexisting multiple allergic conditions were associated with an increased risk of RVO. Thus, it may be advisable to suggest an ophthalmological examination for patients with allergies due to the increased possibility of the occurrence of retinal vascular disease.

Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration.

AIM: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED). METHODS: This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes. RESULTS: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3 (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6. CONCLUSION: Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.

Incidence and Prevalence of Pediatric Noninfectious Uveitis in Korea: A Population-Based Study.

BACKGROUND: Uveitis is less common in children than in adults; however, pediatric uveitis has a relatively severe disease course that affects the quality of life. Although it is important to understand the epidemiological characteristics of pediatric uveitis, few studies have been conducted in large populations without referral bias. This study investigated the nationwide incidence and prevalence of pediatric uveitis in South Korea according to period, age, anatomic type, and systemic associations. METHODS: This nationwide population-based cohort study used data from the Korean National Health Insurance Service from 2002 to 2018. This study included patients younger than 19 years of age with noninfectious uveitis with at least three claims of diagnostic codes of uveitis on separate days with at least once claim of prescription codes of steroid and immunosuppressive agents. All the cases were classified as anterior or non-anterior uveitis, and the overall incidence and prevalence were estimated by age, sex, and period. Patients with noninfectious uveitis were categorized by the presence of associated systemic conditions. RESULTS: A total of 10,862,616 patients over 128,688,078 person-years were evaluated from 2005 to 2016. Overall, 5,368 cases of anterior uveitis and 604 cases of non-anterior uveitis were identified. The incidence and prevalence of pediatric noninfectious uveitis were 4.64 per 100,000 person-years (95% confidence interval [CI], 4.52-4.76) and 8.25 per 100,000 persons (95% CI, 8.09-8.41). Both the incidence and prevalence of pediatric uveitis increased with age. Anterior uveitis accounted for 84.7% of pediatric noninfectious uveitis prevalent cases (6.99 per 100,000 persons). Cases of juvenile idiopathic arthritis (JIA)-associated uveitis accounted for 8.7% (926 cases) of pediatric noninfectious uveitis cases with a prevalence of 0.72 per 100,000 (95% CI, 0.67-0.77). The proportion of systemic associations was higher and JIA-related uveitis accounted for 11.2% (803 cases) of recurrent or chronic noninfectious uveitis cases with a prevalence of 0.62 per 100,000. CONCLUSION: This is the first population-based study investigating the largest population of pediatric patients with uveitis in Korea. The nationwide incidence and prevalence of pediatric noninfectious uveitis in 2005-2016 were 4.64 per 100,000 person-years and 8.25 per 100,000, respectively. The proportion of JIA in pediatric noninfectious uveitis was 8.7%. These population-based study findings provide a better understanding of the public health burden and aid in the planning of health-care strategies for pediatric patients with uveitis.

Risk factors for myopic choroidal neovascularization-related macular atrophy after anti-VEGF treatment.

PURPOSE: The study aimed to evaluate risk factors for macular atrophy (MA) associated with myopic choroidal neovascularization (mCNV) during long-term follow-up after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in highly myopic eyes. METHODS: The medical records of patients who received intravitreal injection of anti-VEGF agents as mCNV treatment and were followed-up for more than 36 months were retrospectively reviewed. The risk factors for the development of mCNV-MA, which is the fovea-involving patchy atrophy lesion adjacent to mCNV, were investigated using the Cox proportional hazard model. RESULTS: A total of 82 eyes (74 patients) were included in the study. The mean age at anti-VEGF treatment was 56.3 ± 12.5 years (range, 26-77), and the mean follow-up period was 76.3 ± 33.5 months (range, 36-154). During follow-up, mCNV-MA developed in 27 eyes (32.9%), and its occurrence was estimated to be 24.5% at 3 years and 37.3% at 5 years after the first anti-VEGF treatment. Old age (hazard ratio [HR] = 1.054, 95% confidence interval [CI]: 1.018-1.091; P = 0.003) and greater CNV size at baseline (HR = 2.396, CI: 1.043-5.504; P = 0.040) were significant factors for mCNV-MA development. Eyes with a thinner subfoveal choroid were more likely to show faster enlargement of the mCNV-MA during follow-up. CONCLUSIONS: In mCNV eyes treated with intravitreal anti-VEGF agents, older age and greater mCNV size at baseline were risk factors for the development of MA during long-term follow-up, which was associated with a poor visual prognosis.

VISUAL PROGNOSTIC VALUE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO AND PLATELET-TO-LYMPHOCYTE RATIO IN BEHÇET UVEITIS.

PURPOSE: To investigate the significance of systemic indicators, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as long-term visual prognostic factors in patients with Behçet uveitis. METHODS: This study comprised 114 eyes from 114 patients diagnosed with Behçet uveitis. Ophthalmologic evaluations and biochemical measurements including NLR and PLR values were consecutively obtained at each visit. Patients were divided into good and poor visual outcome groups, based on the visual acuity of 0.5 logarithm of the minimum angle of resolution in the worse-seeing eyes at the last visit. Factors associated with poor visual outcomes were analyzed, and optimal cutoff values of NLR and PLR were also evaluated. RESULTS: Sixty-six eyes (57.9%) were included in the good visual outcome group. Multivariate regression analysis showed that younger age of onset (odds ratio = 0.939; P = 0.010), longer disease duration (odds ratio = 1.164; P < 0.001), higher maximum NLR (odds ratio = 1.215; P = 0.033), and higher initial PLR (odds ratio = 1.014; P = 0.039) were significantly associated with poor visual outcomes. The optimal cutoff value for patients with poor visual outcome was 5.608 for NLR and 128.078 for PLR. CONCLUSION: A higher maximum NLR and higher initial PLR, as well as a younger age of onset and longer disease duration, were significantly associated with poor visual outcomes. Systemic inflammatory factors might be important indicators of visual prognosis in Behçet uveitis.

Comparison of surgical outcomes after removal of epiretinal membrane associated with retinal break and idiopathic epiretinal membrane.

PURPOSE: To compare the surgical outcomes of epiretinal membranes (ERMs) associated with retinal break and idiopathic ERMs. METHODS: This retrospective study included patients with an idiopathic ERM or an ERM associated with retinal break, who were followed up for ≥ 6 months after ERM removal. The postoperative functional and anatomical outcomes were compared between the groups. RESULTS: A total of 160 and 38 eyes (198 patients) were in the idiopathic and retinal break groups, respectively. There was no significant difference in the baseline anatomical and functional parameters between the groups. At 6 months after surgery and at the final follow-up, best-corrected visual acuity, central foveal thickness, and ectopic inner foveal layer improved significantly in both groups, but there was no significant difference between the groups. In latter 49.0% of patients, tests for metamorphopsia and aniseikonia were performed. There was a significant improvement in the scores of metamorphopsia (0.40 ± 0.38 to 0.27 ± 0.28; p < 0.001) and aniseikonia (6.07 ± 4.46 to 4.11 ± 3.52; p < 0.001) in the idiopathic group at 6 months after surgery, but not in the retinal break group. The idiopathic group had significantly greater circularity of ERM extent compared to the retinal break group (p = 0.025). CONCLUSION: Visual and anatomical improvements after removal of ERMs associated with retinal break and idiopathic ERMs were comparable. However, metamorphopsia and aniseikonia improved only after removal of idiopathic ERMs.

Role of Ultra-widefield Imaging in the evaluation of Long-term change of highly myopic fundus.

PURPOSE: To evaluate the impact of posterior staphyloma identified using ultra-widefield fundus imaging on the long-term progression of myopic maculopathy in highly myopic patients. METHODS: In this observational cohort study, highly myopic patients who were followed up for at least 5 years using ultra-widefield fundus imaging were analysed for fundus abnormalities and the progression of myopic maculopathy based on the International Meta-analysis of Pathologic Myopia classification. RESULTS: This study included 390 eyes (210 patients) with the mean follow-up period of 69.2 ± 7.5 months (range, 60-88). Posterior staphyloma was identified in 198 eyes (50.8%) in the baseline ultra-widefield fundus images. The border of staphyloma was not identified within 50° view circle corresponding to conventional fundus photography in 42 eyes (21.2%) with staphyloma, most of that were wide macular type. Progression of myopic maculopathy during follow-up was observed in 202 eyes (51.8%), and eyes with staphyloma were more likely to show progression compared to those without (142/198 [71.7%] versus 60/192 [31.3%]; p < 0.001). In multivariable regression analysis, the presence of posterior staphyloma was an independent risk factor for the progression of myopic maculopathy (p = 0.005). One or more peripheral retinal lesions were observed in 302 eyes (77.4%) and 321 eyes (82.3%) in the baseline and final ultra-widefield fundus images, respectively. CONCLUSION: Posterior staphyloma was associated with the long-term progression of myopic maculopathy. With a wider field of view, ultra-widefield fundus imaging is useful for identifying the posterior staphyloma and monitoring the progression of myopic maculopathy in highly myopic patients.

Ultra-Widefield Fluorescein Angiography to Monitor Therapeutic Response to Adalimumab in Behcet's Uveitis.

PURPOSE: To investigate the role of ultra-widefield fluorescein angiography (UWFA) for monitoring therapeutic response to adalimumab in patients with Behcet's uveitis. METHODS: Patients with Behcet's uveitis treated with adalimumab for ≥30 weeks were included. Intraocular inflammation, best-corrected visual acuity, systemic medications, and UWFA scores were evaluated. RESULTS: Thirty-eight eyes of 20 patients were included. Significant decreases in grading of anterior chamber cells and vitreous haze were observed at 6, 14, and 30 weeks after adalimumab administration (p < .001 for all). UWFA scores on vascular and capillary leakage were decreased at week 6 and further improved at weeks 14 and 30. Moreover, UWFA score further decreased at 14 and 30 weeks, even after manifest inflammation became quiescent at 6 weeks. (p = .004 and 0.001, respectively). CONCLUSION: UWFA scores significantly improved in Behcet's uveitis patients treated with adalimumab, and further improvement of UWFA scores was found in patients with a clinically quiescent inflammatory state.

Influence of postoperative ectopic inner foveal layer on visual function after removal of idiopathic epiretinal membrane.

PURPOSE: To investigate the functional and anatomical parameters and their postoperative changes according to the ectopic inner foveal layer (EIFL) staging scheme for idiopathic epiretinal membrane (ERM). METHODS: In this prospective study, patients with idiopathic ERM underwent pars plana vitrectomy and ERM removal, and were followed-up for 6 months. The associations of EIFL with pre- and postoperative functional and anatomical parameters were analyzed. RESULTS: A total of 84 eyes (84 patients) were included: 39 (46.4%), 33 (39.3%), and 12 (14.3%) as EIFL stages 2, 3, and 4, respectively. At 6 months after surgery, the mean best-corrected visual acuity (BCVA) significantly improved in all EIFL stages (P ≤ 0.003); however, metamorphopsia improved only in eyes with EIFL stage 2 (P = 0.039) and 3 (P = 0.011). The aniseikonia and foveal avascular zone (FAZ) area showed no significant postoperative changes in any of the EIFL stages. Both preoperatively and during 6 months after surgery, the EIFL stage showed a significant correlation with BCVA (P ≤ 0.033), metamorphopsia (P ≤ 0.008), central macular thickness (P < 0.001), and FAZ parameters (P ≤ 0.016) at each time point, but not with aniseikonia. Significant correlations of EIFL thickness with BCVA (P = 0.028) and metamorphopsia (P = 0.006) before surgery were not persistent after surgery. CONCLUSION: Both pre- and postoperatively, the staging of EIFL, rather than its thickness, is a simple and adequate surrogate marker for visual acuity and metamorphopsia in eyes with idiopathic ERM.

Subretinal versus intravitreal administration of human CD34+ bone marrow-derived stem cells in a rat model of inherited retinal degeneration.

BACKGROUND: To evaluate whether subretinal or intravitreal injection of human CD34+ bone marrow-derived stem cells (BMSC) can have protective effects on retinal degeneration that may be enhanced by coadministration of exosomes harvested from human bone marrow mesenchymal stem cells (MSCs). METHODS: Human CD34+ cells were harvested from the mononuclear cell fraction of bone marrow using magnetic beads and labeled with EGFP. Exosomes were harvested from cultured human MSCs under hypoxic conditions. Royal College of Surgeons (RCS) 3-weeks-old rats, immunosuppressed with cyclosporine A, received subretinal or intravitreal injection of CD34+ cells (50,000 cells), CD34+ cells with exosomes (50,000 cells+10 µg), exosomes alone (10 µg), or PBS. Retinal function was examined using electroretinography (ERG), and the eyes were harvested for histologic and immunohistochemical analysis. RESULTS: The b-wave amplitude of ERG at 2 weeks after injection was significantly higher in eyes with subretinal or intravitreal CD34+ BMSC alone or in combination with exosomes when compared to PBS injected eyes or untreated contralateral eyes. At 4 weeks after injection, the ERG signal decreased in all groups but eyes with subretinal CD34+ BMSCs alone or combined with exosomes showed partially preserved ERG signal and preservation of the outer nuclear layer of the retina near the injection site on histology when compared to eyes with PBS injection. Immunohistochemical analysis identified the human cells in the outer retina. Subretinal or intravitreal exosome injection had no effect on retinal degeneration when administered alone or in combination with CD34+ cells. CONCLUSIONS: Both subretinal and intravitreal injection of human CD34+ BMSCs can provide functional rescue of degenerating retina, although the effects were attenuated over time in this rat model. Regional preservation of the outer retina can occur near the subretinal injection site of CD34+ cells. These results suggest that CD34+ cells may have therapeutic potential in retinal degeneration.

Decreased choroidal and scleral thicknesses in highly myopic eyes with posterior staphyloma.

In this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 µm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = - 0.548 to - 0.357, all P < 0.001) and greater macular curvatures (r = - 0.542 to - 0.305, all P < 0.001). The CT and ST were significantly thinner in eyes with posterior staphyloma than in those without at all measurement points (all P ≤ 0.006) but did not differ between eyes with the wide macular and narrow macular type of staphyloma. Eyes with myopic maculopathy of category ≥ 3 according to the International Meta-Analysis for Pathologic Myopia classification had significantly thinner CTs and STs than those with category ≤ 2 (all P ≤ 0.005). In highly myopic eyes, a decrease in the CT and ST was more pronounced in eyes with more structural changes, such as longer axial length, steeper macular curvature, and the presence of posterior staphyloma.

Long-term results of rescue photodynamic therapy for type 1 neovascularization refractory to anti-vascular endothelial growth factor.

PURPOSE: To evaluate long-term results of photodynamic therapy (PDT) as a rescue treatment in patients with type 1 neovascularization refractory to intravitreal anti-vascular endothelial growth factor (VEGF). METHODS: Patients who underwent reduced-fluence PDT for refractory type 1 neovascularization, which showed persistent subretinal and/or intraretinal fluid after three or more consecutive anti-VEGF treatments, and were followed up for ≥24 months were reviewed. RESULTS: Seventy-eight eyes of 78 patients were included, and 37 (47%) were classified as polypoidal choroidal vasculopathy (PCV). The mean number of anti-VEGF injections before rescue PDT was 8.5 ± 5.4, and the mean follow-up period after rescue PDT was 74.0 ± 29.4 months. At 3 months after rescue PDT, exudation completely resolved in 55 (71%) patients and vision significantly improved (p = 0.021). Resolution of exudation was associated with choroidal vascular hyperpermeability [odds ratio (OR), 3.82; p = 0.031] and lower maximal height of pigment epithelial detachment (OR, 0.69; p = 0.018). In these patients, exudation recurred in 49 (89%) after mean period of 13.5 months. Vision significantly worsened at 24 months after rescue PDT, and thereafter, and the vision decrease was more prominent in patients with PCV. Rescue PDT could be repeated for recurrent or persistent exudation without increasing the risk of complications. CONCLUSION: In patients with type 1 neovascularization refractory to anti-VEGF, reduced-fluence PDT is an effective and safe rescue treatment. Therapeutic efficacy wore off during long-term follow-up, but rescue PDT may be repeated safely.

Evaluation of the Safety and Efficacy of Selective Retina Therapy Laser Treatment in Patients with Central Serous Chorioretinopathy.

PURPOSE: To assess the safety and efficacy of selective retina therapy (SRT) using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback systems in patients with idiopathic central serous chorioretinopathy (CSC). METHODS: This randomized clinical trial enrolled patients having at least 3-month symptom of CSC. From month 3 visit, all subjects in both groups were eligible for SRT retreatment if they showed persistent or recurrent subretinal fluid (SRF). The primary outcome was complete resolution of SRF by optical coherence tomography at 3 months after treatment. The secondary outcomes were changes in SRF, central macular thickness (CMT) and best-corrected visual acuity at the 1-, 3-, and 6-month examinations. RESULTS: Sixty-eight CSC patients were included (SRT, 31; control, 37). After 1 and 3 months, complete resolution of SRF was achieved in 25.8% and 54.8% of SRT group and 17.6% and 35.1% of controls. The differences were not statistically significant (p = 0.424 and p = 0.142, respectively). However, mixed model for repeated measures analyses showed that the reduction of SRF and CMT were observed earlier in SRT group than in the sham group (least squares mean difference, -59.7 µm; 95% confidence interval, -98.2 to -21.2; p = 0.0029; least squares mean difference -67.0 µm; 95% confidence interval, -104.8 to -29.2; p = 0.0007, respectively). Significant reduction of SRF (≥50% reduction from baseline) was more frequently observed in SRT group (80.6%) than the sham group (44.1%) at month 1 (p = 0.007). Early reduction of SRF and CMT was more abundant in SRT group with symptom duration less than 6 months. Treatment related serious adverse events were not observed. CONCLUSIONS: SRT using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback system was safe in this trial and effective for early resolution of SRF in the CSC patients. Early intervention with SRT can be a safe alternative for patients with acute symptomatic CSC.

Effects of Bifocal versus Trifocal Diffractive Intraocular Lens Implantation on Visual Quality after Cataract Surgery.

PURPOSE: To compare the effects of bifocal versus trifocal diffractive intraocular lens (IOL) implantation on visual quality after phacoemulsification in patients with cataracts. METHODS: Eighty-eight eyes from 63 patients were analyzed. Trifocal (AT LISA tri 839MP), bifocal (AcrySof IQ ReSTOR) and bifocal (Tecnis MF ZLB00) IOLs were implanted into 53, 18, and 17 eyes, respectively. Uncorrected distance, intermediate and near visual acuity, refractive errors, contrast sensitivity, and patient satisfaction were measured at 1 week and 1 month after surgery. Refractive error was converted to a spherical equivalent and compared to predicted refraction calculated by IOL calculation formulas. RESULTS: Uncorrected distance, intermediate, and near visual acuity did not differ significantly between groups. One month after surgery, the mean refractive errors were -0.07 diopters (D) in the AT LISA tri 839MP group, +0.18 D in the AcrySof IQ ReSTOR group, and +0.31 D in the Tecnis MF ZLB00 group (p < 0.001). The predictive accuracy of IOL calculation formulas did not differ between groups. Contrast sensitivity, satisfaction, and spectacle independence in the trifocal group were comparable with those of the two bifocal groups. CONCLUSIONS: Trifocal IOL and two different types of bifocal IOL implantation were all effective for improving visual quality, although refractive error in patients with trifocal IOL shows myopic tendencies.

Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory Response.

The mammalian target of rapamycin (mTOR) signaling is critical to the regulation of stem cell maintenance and function in a cell-type and context-dependent manner. However, the effects of mTOR signaling on corneal epithelial stem cells (CESCs) under inflammatory conditions are not clear. Here, we demonstrate that mTOR inhibition with rapamycin promotes apoptosis of CESCs in a mouse model of sterile inflammation-induced CESC deficiency, and thereby aggravates the disease. Apoptosis induction in CESCs by rapamycin is not due to direct effect of rapamycin on the cells, but mediated by increase in neutrophilic inflammation. The interleukin (IL)-10/signal transducer and activator of transcription 3 anti-inflammatory pathway was downregulated in a Toll-like receptor 2-independent manner after rapamycin treatment and IL-10 replenishment abrogated the effects of rapamycin on inflammation and CESC apoptosis. Hence, our data reveal that the mTOR signaling is implicated in the control of the pro-inflammatory and anti-inflammatory balance in the cornea and that mTOR inhibition with rapamycin is detrimental to CESCs by accelerating inflammation-induced collateral damage to the cells. Stem Cells 2019;37:1212-1222.

Increased expression of IL-33 in rosacea skin and UVB-irradiated and LL-37-treated HaCaT cells.

Rosacea is one of the most common dermatoses of adults. Although the detailed pathophysiology remains unknown, it is thought that rosacea is caused by a consistently aberrant, innate immune response, and that LL-37 plays an important role. However, involvement of the inflammatory cytokine IL-33 has not yet been studied. We explored the role played by IL-33 in the pathophysiology of rosacea. First, we immunohistochemically evaluated the expression of IL-33 and its receptor (ST2) in rosacea skin. Second, we exposed HaCaT cells to ultraviolet B (UVB) irradiation in the presence or absence of LL-37 and measured the expression of proinflammatory cytokines including IL-33. We also analysed VEGF (vascular endothelial growth factor) mRNA expression and protein release after costimulation of HaCaT cells by LL-37 and IL-33. Immunohistochemically, IL-33 expression was enhanced in the skin of rosacea patients, especially with erythematotelangiectatic subtype. In vitro, UVB and LL-37 synergistically increased mRNAs expression of proinflammatory cytokines, especially IL-33 and IL-1ß. IL-33 protein release was also synergistically increased by LL-37 and UVB treatment. LL-37 and IL-33 stimulated VEGF mRNA expression and VEGF release from HaCaT cells. Our findings suggest that rosacea skin with abundant LL-37 may robustly produce and release IL-33 when exposed to UV radiation. IL-33 may participate in the angiogenesis and vasodilation of rosacea skin by enhancing VEGF release.

Ophthalmologic Features of Lennox-Gastaut Syndrome.

PURPOSE: To describe the characteristics and frequency of ophthalmologic findings in patients with Lennox-Gastaut syndrome (LGS). METHODS: The medical records of patients diagnosed with LGS at Seoul National University Children's Hospital from January 2004 to August 2014 were retrospectively reviewed. The records of 34 patients (mean age ± standard deviation, 2.66 ± 3.51 years; male, 58.8%) were reviewed. The primary measure was the incidence of ophthalmologic manifestations. RESULTS: Of the 34 patients, 88.2% had at least one ocular abnormality. Refractive error (52.9%) was the most frequently observed ophthalmologic manifestation in patients with LGS, followed by strabismus (32.4%), cortical visual impairment (23.5%), and retinopathy of prematurity (8.8%). Among these cases, seven patients had exotropia and three had esotropia. CONCLUSIONS: LGS is a childhood-onset epileptic encephalopathy with variable ophthalmologic manifestations, the most frequent being refractive errors. Patients with suspected LGS should be examined regularly because ophthalmological features can change during their disease course.

Optic Disc Swelling After Intraocular Pressure Lowering Treatment in Acute Primary Angle Closure.

PURPOSE OF THE STUDY: The purpose of the study was to report cases with acute primary angle closure where optic disc swelling was documented after intraocular pressure (IOP) lowering by laser iridotomy. PATIENTS AND METHODS: Two patients with acute primary angle closure underwent funduscopic examination of the optic disc and spectral-domain optical coherence tomography circumpapillary scanning at the time of acute primary angle closure attack before laser iridotomy, and after the laser iridotomy treatment. RESULTS: Optic disc swelling was developed in both patients following IOP lowering by laser iridotomy, which was documented by spectral-domain optical coherence tomography imaging as a diffuse thickening of the circumpapillary retinal nerve fiber layer. CONCLUSIONS: This is the first report demonstrating a temporal relationship between IOP lowering and optic disc swelling in patients with acute primary angle closure. Optic disc swelling documented after acute episode of acute primary angle closure may suggest choroidal effusion or axoplasmic overflow associated with sudden IOP lowering, rather than coexistence of other optic neuropathy.