The impact of visual function on staircase use performance in glaucoma.

OBJECTIVES: This cross-sectional study aimed to investigate the relationship between visual function and staircase use in glaucoma. METHODS: Overall, 181 patients with glaucoma with a best-corrected visual acuity ≥20/400 were classified into mild to moderate (mean deviation [MD] ≥ -12 dB) and advanced (MD < -12 dB) groups, according to 24-2 VF of the worse eye. Staircase use evaluation included stair descent and ascent time (SDT/SAT) and self-reported stair difficulty. Correlations between staircase use and visual function were analysed, including binocular visual acuity, integrated visual field (IVF), and binocular contrast sensitivity (CS). Linear and logistic regression adjusted by age, sex, and comorbidities inspected the effect of visual parameters on SDT/ SAT and stair difficulty. RESULTS: Visual function best correlated with SDT among staircase use. In mild to moderate glaucoma, area under the log CS function (AULCSF) (ß = -1.648, P = 0.031) was the only visual factor significant for SDT (adjusted R2 = 0.106), whereas AULCSF (ß = -1.641, P = 0.048) and MD of IVFINF0-24 (ß = -0.089, P = 0.013) were associated with SDT in advanced glaucoma (adjusted R2 = 0.589). The AULCSF was the only significant visual parameter related to SAT (ß = -1.125, P = 0.019) and stair difficulty (adjusted odds ratio = 0.003; 95% confidence interval, 0-0.302; P = 0.013). CONCLUSIONS: SDT provides a higher correlation with visual function than self-reported stair difficulty. Patients with impaired CS or inferior IVF defects should be advised on stair safety and referred to low-vision services.

Autophagy deficiency protects against ocular hypertension and neurodegeneration in experimental and spontanous glaucoma mouse models.

Glaucoma is a group of diseases that leads to chronic degeneration of retinal ganglion cell (RGC) axons and progressive loss of RGCs, resulting in vision loss. While aging and elevated intraocular pressure (IOP) have been identified as the main contributing factors to glaucoma, the molecular mechanisms and signaling pathways triggering RGC death and axonal degeneration are not fully understood. Previous studies in our laboratory found that overactivation of autophagy in DBA/2J::GFP-LC3 mice led to RGC death and optic nerve degeneration with glaucomatous IOP elevation. We found similar findings in aging GFP-LC3 mice subjected to chronic IOP elevation. Here, we further investigated the impact of autophagy deficiency on autophagy-deficient DBA/2J-Atg4bko and DBA/2J-Atg4b+/- mice, generated in our laboratory via CRISPR/Cas9 technology; as well as in Atg4bko mice subjected to the experimental TGFß2 chronic ocular hypertensive model. Our data shows that, in contrast to DBA/2J and DBA/2J-Atg4b+/- littermates, DBA/2J-Atg4bko mice do not develop glaucomatous IOP elevation. Atg4b deficiency also protected against glaucomatous IOP elevation in the experimental TGFß2 chronic ocular hypertensive model. Atg4 deletion did not compromise RGC or optic nerve survival in Atg4bko mice. Moreover, our results indicate a protective role of autophagy deficiency against RGC death and ON atrophy in the hypertensive DBA/2J-Atg4b+/- mice. Together, our data suggests a pathogenic role of autophagy activation in ocular hypertension and glaucoma.

Relationship between the Macular Microvasculature and Central Visual Field Sensitivity in Patients with Advanced Glaucoma.

PURPOSE: To evaluate the relationship between central visual field sensitivity (cVFS) and the structural parameters in patients with advanced glaucoma. DESIGN: Cross-sectional study. METHODS: In total, 226 eyes of 226 patients with advanced glaucoma were classified into the "minor central defect" (mean deviation on 10-2 visual field test [MD10] > -10 dB) and "significant central defect" (MD10 ≤ -10 dB) groups. We examined the structural parameters using RTVue OCT and angiography, including the retinal nerve fiber layer, ganglion cell complex, peripapillary vessel density (VD), and superficial and deep macular VD (mVD). The assessment of cVFS included MD10 and the mean deviation of the central 16 points on the 10-2 VF test (MD16). We used Pearson correlation and segmented regression to assess the global and regional relationships between the structural parameters and cVFS. MAIN OUTCOME MEASURES: Correlation between structural parameters and cVFS. RESULTS: In the minor central defect group, the best global correlations existed between the superficial macular and parafoveal mVD and MD16 (r = 0.52 and 0.54, P < 0.001). In the significant central defect group, superficial mVD best correlated with MD10 (r = 0.47, P < 0.001). Segmented regression between superficial mVD and cVFS revealed no breakpoint was found as MD10 declined, but a breakpoint was identified at -5.95 dB for MD16, which was statistically significant (P < 0.001). The regional correlations between the grid VD and sectors of the central 16 points were significant (r = 0.20-0.53, P= 0.010 ∼P < 0.001). CONCLUSIONS: The fair global and regional relationships between mVD and cVFS suggest that mVD may be beneficial for monitoring cVFS in patients with advanced glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Host Immune Response and Associated Clinical Features in a Primary Cytomegalovirus Eye Infection Model Using Anterior Chamber Inoculation.

Purpose: To investigate the pathogenesis of cytomegalovirus (CMV)-associated anterior segment infection in immunocompetent hosts and evaluate the effects of ganciclovir and glucocorticoid treatment in management of the disease. Methods: We used an inoculation model to reproduce CMV anterior segment infection in immunocompetent rats. Flow cytometry, cytokine analysis, histopathological sections, and quantitative polymerase chain reaction were performed to investigate the immune response after CMV infection. The effects of ganciclovir and glucocorticoid treatment were also assessed. Results: Anterior chamber inoculation of CMV in rats provoked characteristic pathological features of human CMV anterior segment infection. The innate and adaptive immunity sequentially developed in an anterior segment after inoculation, and the elevation of intraocular pressure (IOP) was highly associated with ocular infiltration and inflammation. Early ocular immune response reduced virus DNA in the anterior segment and alleviated viral lymphadenopathy. Early intervention with ganciclovir enhanced the release of cytokines associated with T response and facilitated recruitment of NKT and T cells in drainage lymph nodes. Glucocorticoid treatment, alone or combined with ganciclovir, decreased elevation of IOP but also impeded DNA clearance. Conclusions: The inoculation model reproduced characteristic pathological features of human CMV anterior segment infection. The use of glucocorticoid in current practice may hinder viral clearance, and ganciclovir therapy can assist cytokine expression to combat the virus.

Evaluation of the association between macular damage and disability glare in patients with advanced glaucoma.

PURPOSE: This study aimed to investigate the factors associated with disability glare in patients with advanced glaucoma and evaluate the impact of disability glare on the vision-related quality of life. METHODS: We prospectively studied 225 eyes (225 patients) with advanced glaucoma. The visual function was evaluated using the 10-2 and 24-2 Humphrey visual field (VF) (Dublin, California) and contrast sensitivity test. Structural parameters were obtained using RTVue optical coherence tomography and angiography (Fremont, California). Significant loss of macular vessel density (mVD) was defined as VD < 30%. Each participant completed the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) and questions regarding subjective symptoms of glare. RESULTS: Fifty-six patients (24.9%) experienced glare and had a lower NEI-VFQ-25 composite score (P = 0.017). The average retinal nerve fiber layer and ganglion cell complex thickness and mean deviation (MD) in the 24-2 VF test were not associated with glare. Significant superior or inferior mVD loss (P < 0.001; odds ratio [OR], 3.45; and 95% confidence interval [CI], 1.83-6.55), lower logarithmic contrast sensitivity at 0.75 cycles/degree (P < 0.001; OR, 0.27; and 95% CI, 0.13-0.56), and worse MD in the 10-2 VF test (P < 0.001; OR, 0.93; and 95% CI, 0.89-0.97) showed an association with glare. CONCLUSION: In advanced glaucoma, central VF defect and mVD loss are associated with disability glare, which negatively impacts vision-related quality of life.

Transient Bacteremia Promotes Catheter-Related Central Venous Thrombosis through Neutrophil Extracellular Traps.

Formation of intravenous catheter-related thrombosis leads to central venous stenosis in patients requiring renal replacement therapy or chemotherapy infusion, yet the triggers or mechanisms remain unclear, especially in patients without symptoms of infection. In this study, we found that neutrophil extracellular traps (NETs) could be detected in the fibrin sheaths from dialysis patients without clinical manifestations of infection. Confocal microscopy revealed bacteria imbedded in NETs in the fibrin sheaths. Thirty-nine of 50 (78%) fibrin sheath specimens contained bacteria detectable by 16S ribosomal RNA genome typing with a predominance of Staphylococcus aureus (69%). In rat models, transient bacteremia of S. aureus induced NETs in enlarged fibrin sheaths, and treatment with DNase I alone significantly reduced both NET and fibrin sheath formation surrounding the catheter. Therefore, transient bacteremia could be a silent trigger that induces NET-related immunothrombosis enhancing catheter-related central venous stenosis.

Relationship Between Macular Microvasculature and Visual Acuity in Advanced and Severe Glaucoma.

PURPOSE: To evaluate the correlation between structural parameters and visual acuity (VA) in advanced glaucoma. DESIGN: Prospective, cross-sectional study. METHODS: A total of 238 eyes from 238 patients (82 were men and mean ± SD age was 59.9 ± 13.8 years) from a tertiary center were divided into an advanced (mean deviation of 24-2 visual field tests from -12.01 to -20.0 dB) and severe (< -20 dB) glaucoma group. Structural parameters were obtained by RTVue (Optovue Inc) optical coherence tomography and angiography. Pearson correlation, partial correlation adjusted for age and axial length, and receiver operating characteristic curves to detect decreased VA (<20/25) were performed. RESULTS: In the advanced glaucoma group (133 eyes), superficial (Pearson correlation coefficient, r = -0.46, P < .001; partial correlation coefficient, r' = -0.30, P < .001) and deep macular vessel densities (VDs) (r = -0.47, P < .001; r' = -0.30, P < .001) showed highest correlation with VA. The area under the receiver operating characteristic curves of the superficial parafoveal/macular VDs were 0.816 (95% CI, 0.735-0.897) and 0.808 (95% CI, 0.725-0.891), respectively. In the severe glaucoma group (105 eyes), deep nasal grid VD (r = -0.31, P = 0.002; r' = -0.35, P < .001) showed highest correlation with VA. Deep macular VD showed better correlation with VA than other structural parameters. The area under the receiver operating characteristic curves of deep macular VD and deep nasal grid VD were 0.740 (95% CI, 0.632-0.849) and 0.748 (95% CI, 0.640-0.857), respectively. CONCLUSIONS: Macular VD showed better correlation with VA in advanced glaucoma. Deep macular VD, especially nasal grid, may be a promising structural parameter in severe glaucoma.

Relationship of axial length and corneal biomechanical properties with susceptibility to unilateral normal-tension glaucoma.

PURPOSE: Corneal biomechanics, reflecting structural vulnerabilities of the eyeball, may participate in the pathogenesis of unilateral normal-tension glaucoma. This study investigated the pathophysiology of unilateral normal-tension glaucoma using Corvis ST (OCULUS Optikgeräte GmbH) and other ocular characteristics. METHODS: Eighty-three patients with normal-tension glaucoma with unilateral visual field loss and structurally unaffected fellow eyes and 111 healthy controls were included in this prospective study. Dynamic corneal response parameters, intraocular pressure measured by rebound tonometry, central corneal thickness, and axial length were assessed on the same day. Measurements were compared between affected eyes, unaffected fellow eyes, and control eyes. Risk factors for normal-tension glaucoma and unilateral involvement were the main outcome measures. RESULTS: A shorter first applanation time (adjusted odds ratio, 0.061; 95% confidence interval, 0.018-0.215) and a larger peak distance (adjusted odds ratio, 4.935; 95% confidence interval, 1.547-15.739) were significant risk factors for normal-tension glaucoma and were associated with greater glaucoma severity (both P < 0.001). Axial length (adjusted odds ratio, 29.015; 95% confidence interval, 4.452-189.083) was the predominant risk factor for unilateral involvement in patients with normal-tension glaucoma. CONCLUSION: The eyes with normal-tension glaucoma were more compliant than healthy eyes. Axial elongation-associated optic nerve strain may play an important role in unilateral normal-tension glaucoma with similar corneal and scleral biomechanics in both eyes.

Anti-glaucoma agents-induced pseudodendritic keratitis presumed to be herpetic simplex keratitis: a clinical case series.

Anti-glaucoma agents-induced corneal toxicity may be misdiagnosed as herpetic simplex keratitis (HSK). In our study, nineteen glaucoma patients were presumed to have HSK before referral. Corneal lesions were classified into (I) linear pseudodendritic lesions formed by elevated opacified cells, (II) linear pseudodendritic lesions formed by grouped superficial punctate keratitis (SPK), (III) satellite full-thickness epithelial defects, (IV) satellite lesions formed by elevated opacified cells, and (V) geographic lesions formed by grouped SPK. We observed thirty-one events, with 15 in the lower and 16 in the central corneas. There were 21 (67.7%) type II, five (16.1%) type V, two (6.5%) of each for types III and IV, and one (3.2%) type I events. Among linear lesions (types I and II), 17 (77.3%) had horizontal and 5 (22.7%) had curvilinear orientations. Exposure duration to the last-added anti-glaucoma agent was three days to 14.5 years. About half of the events (16/31, 51.6%) used prostaglandin analogues, and 30/31 (96.8%) applied benzalkonium chloride (BAK)-containing agents. All lesions resolved within two months after decreasing offending medications or enhancing protection of ocular surface. In conclusion, anti-glaucoma agents-induced pseudodendritic keratitis presents majorly in central-lower cornea as horizontally linear lesions, and BAK-containing agents are observed in the most events.

High Risk for Attention-Deficit Hyperactive Disorder in Children with Strabismus: A Nationwide Cohort Study from the National Health Insurance Research Database.

Strabismus is associated with amblyopia and a lower quality of life. Attention-deficit hyperactivity disorder (ADHD) is common among children and adolescents, and influences their academic, vocational, and social life. Previous studies have suggested an association between strabismus and ADHD. Using data from the Taiwan National Health Insurance Research Database between 2000 and 2010, we performed a large-scale cohort study comparing the incidence, risk factors, and severity of ADHD in children with and without strabismus. A total of 2049 patients <18 years old with newly diagnosed strabismus (esotropia: 404; exotropia: 1645) were identified, and 8196 age- and sex-matched controls without strabismus were also included. After an average of 6.5 ± 2.9 years of follow-up, the incidence of ADHD per 1000 person-years was 5.39 in the strabismus group (esotropia: 9.93; exotropia: 4.11) and 3.23 in the control group. The cumulative incidence of ADHD was significantly greater in the esotropia (hazard ratio [HR]: 2.04; 95% confidence interval [CI]:1.36-3.06; p = 0.0007) and exotropia groups (HR: 1.44; 95% CI: 1.03-2.03; p = 0.038) than in the controls. Patients with strabismus had more comorbidities than those without (p < 0.05). In summary, this large-scale study found a higher cumulative incidence of ADHD in patients with strabismus, especially in those with esotropia.

Ocular Surface Disease in Glaucoma Patients Randomized to Benzalkonium Chloride-Containing Latanoprost and Preservative-Free Bimatoprost.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to receive BAK-containing latanoprost (Xalatan) or preservative-free bimatoprost (Lumigan PF). Intraocular pressure (IOP), basal Schirmer's test, noninvasive keratograph tear-breakup time (TBUT), conjunctival redness score (R score), OSD index (OSDI), and corneal Oxford staining were recorded and compared between the 2 groups at 1-month and 4-month visits. The influence of BAK was analyzed by a generalized estimating equation model. Results: We enrolled 74 and 76 eyes treated with latanoprost and bimatoprost, respectively. The IOP decreased in both groups, although greater reduction was observed for latanoprost (13.95 vs. 15.42 mmHg, P = 0.0264). There was a significantly negative association between tear flow and latanoprost use (ß = -0.763, P = 0.0243). The first and average TBUT did not show intergroup differences, but the area with unstable tear film increased with latanoprost use and showed marginal significance at 4-month visit (9.33% vs. 5.94% P = 0.055). In both groups, OSDI decreased, whereas Oxford stain increased over time, and R scores showed improvement after transient increase in the first month. The bimatoprost group had significantly worse conjunctival hyperemia, whereas a negative association with conjunctival hyperemia was revealed for latanoprost use (R score-bulbar nasal: ß = -0.045, P = 0.0423). Conclusions: BAK-containing latanoprost was associated with decreased tear secretion and may be associated with tear-film instability, whereas bimatoprost was associated with worse conjunctival hyperemia. Ocular surface side effects should be considered when prescribing BAK-containing medication to glaucoma patients.

Long-term structural and functional outcomes of primary congenital glaucoma.

PURPOSE: To investigate the clinical characteristics and long-term outcomes of primary congenital glaucoma (PCG) patients. METHODS: In this retrospective, longitudinal, cohort study, PCG patients with reliable visual field (VF) tests and optical coherence tomography (OCT) were included. Disease progression was detected using guided progression analysis with OCT and the change analysis of mean deviation (MD) slope with VF tests. Factors associated with the disease progression and visual prognosis were analyzed. RESULTS: Twenty-nine eyes from 11 bilateral and 7 unilateral PCG patients were enrolled. LogMAR visual acuity declined (0.15 vs. 0.40, P < 0.001). The change rate of the average retinal nerve fiber layer thickness was - 0.83 ± 1.45 µm/year, and 28% of eyes showed glaucoma progression on OCT. The median of the MD slope was 0.16 (- 1.19 to 1.07) dB/year, and 14% of eyes showed glaucoma progression on the VF test. Higher average intraocular pressure (IOP) (P = 0.046) and IOP fluctuation (P = 0.031) predicted disease progression. None of the fellow eyes of unilateral PCG patients developed glaucoma during the follow-up. At last, 59% of eyes had visual acuity > 20/70, and 31% had MD > - 6 dB. Patients with worse baseline visual acuity (P = 0.027), worse baseline MD (P < 0.001), and smaller neuroretinal rim area (P < 0.001) showed worse final MD values. CONCLUSIONS: Aggressive IOP control is necessary to prevent structural and functional decline in PCG patients. Their fellow eyes are not at risk of glaucoma. Baseline neuroretinal rim area can predict the functional outcome.

Posture-Related Changes of Intraocular Pressure in Patients With Acute Primary Angle Closure.

Purpose: To evaluate the posture-related change in intraocular pressure (IOP) of eyes with angle-closure disease and the associated factors. Methods: Eyes were prospectively enrolled and divided into three groups: eyes with acute primary angle-closure (APAC), fellow eyes of acute primary angle-closure (FAPAC), and eyes with nonacute primary angle-closure disease (PACD). All of them had been treated with laser peripheral iridotomy. IOP was measured in the sitting, supine, and lateral decubitus positions (LDP) five minutes after posture change. Anterior chamber angle parameters and angle-closure mechanism were evaluated by anterior segment optical coherence tomography. Results: Forty-four eyes were enrolled into each group. APAC eyes showed more LDP-Sitting IOP increase than fellow eyes (5.7 ± 2.7 vs. 2.2 ± 1.4 mm Hg, P < 0.001) and nonacute PACD eyes (3.6 ± 2.0 mm Hg, P < 0.001). LDP-sitting IOP change was higher in eyes with exaggerated lens vault (having shallow anterior chamber and volcano-like iris-lens configuration) than in those without it (APAC: 6.3 ± 2.6 vs. 3.9 ± 2.1 mm Hg, P = 0.011). Linear regression revealed that LDP-sitting IOP change in the APAC group was negatively associated with angle opening distance (AOD), trabecular iris space area, scleral spur angle, and anterior chamber depth (ACD1000). With multivariable stepwise regression analysis, AOD750 remained statistically significant (beta-coefficient = -8.36, P = 0.014). Conclusions: APAC eyes had significant posture-related IOP changes, associated with narrower angle structures and exaggerated lens vault.

Assessment of ocular surface disease in glaucoma patients with benzalkonium chloride-preserved latanoprost eye drops: a short-term longitudinal study.

PURPOSE: To prospectively evaluate the effect of benzalkonium chloride (BAK)-preserved latanoprost on ocular surface damage and identify the associated risk factors among treatment-naive glaucoma patients. METHODS: The basal Schirmer's test results, corneal Oxford staining score, non-invasive keratograph tear-breakup time, oculus hyperemia index score (objective metrics), and ocular surface disease index (OSDI) questionnaire (subjective metric) were evaluated at baseline, 1 month, and 4 months after receiving latanoprost eye drops. Associated risk factors were assessed by multivariate linear regression. RESULTS: Seventy-four eyes (44 patients) were enrolled. Basal Schirmer's test tear-flow and Oxford scores gradually deteriorated (ß = -0.14, P = 0.001 and ß = 0.1, P < 0.001, respectively). The percentage of unstable tear-film (breakup time < 10 s) increased significantly at 4 months (6.21% vs 9.11%, P = 0.042). Hyperemic scores increased significantly at 1 month and normalized at 4 months (P = 0.01 and P = 0.16, respectively); total OSDI scores tended to improve (ß = -0.76, P = 0.06). Older age was associated with additional corneal Oxford staining (P = 0.005); female sex was associated with increased unstable tear-film scores (P = 0.01). Artificial tear use was associated with a smaller decrease in basal Schirmer's test values (P = 0.01) and a smaller increase in unstable tear-film scores (P = 0.02). CONCLUSIONS: Preserved latanoprost eye drops affected ocular surface changes in glaucoma patients through decreased basal tear secretion. Artificial tears represent an early intervention in vulnerable glaucoma patients with reduced tear secretion and impaired tear-film stability.

Refractive outcomes of cataract surgery in patients receiving trabeculectomy-a comparative study of combined and sequential approaches.

BACKGROUND: Cataract surgery in combination with or after trabeculectomy is often required for improving vision in glaucoma patients. Intraocular pressure (IOP) changes may influence refractive outcomes after cataract surgery. We compared refractive outcomes of the combined and sequential approaches in managing glaucoma and cataract. METHODS: This retrospective case-control study included 52 patients (57 eyes) who underwent phacotrabeculectomy (combined group) and 39 patients (42 eyes) who underwent phacoemulsification at least three months post-trabeculectomy (sequential group). The IOP and refraction prediction error were compared at three months after cataract surgery. Univariate regression analyses were used to assess risk factors for the postoperative refraction prediction error. RESULTS: Anti-glaucomatous medications were not administered to either group. The mean postoperative IOP (12.96 vs. 13.80 mmHg; P = .392), refraction prediction error (-0.32 ± 1.53 vs. -0.47 ± 1.14 D, P = .594), mean absolute error (1.02 ± 1.18 vs. 0.8 ± 0.93 D, P = .320), and surgically induced astigmatism (1.85 ± 1.40 vs. 2.16 ± 1.16 D, P = .161) did not differ significantly between the combined and sequential groups. In the sequential group, the refraction prediction error correlated to the IOP change, with a 1-mm Hg rise resulting in a -0.07-diopter shift between the expected and observed refraction (r = -0.380, R2 = 0.144, P = .013); no such correlation was observed in the combined group. CONCLUSION: Both approaches resulted in similar effective IOP control and accurate intraocular lens predictability. The IOP change affected the postoperative refraction prediction error only in the sequential approach.

Evolution of the Prevalence of Myopia among Taiwanese Schoolchildren: A Review of Survey Data from 1983 through 2017.

PURPOSE: The aim of this study was to evaluate the changes in the prevalence of myopia in Taiwanese schoolchildren over the past few decades and to analyze the risk factors for myopia. DESIGN: Analysis of 8 consecutive population-based myopia surveys conducted from 1983 through 2017. PARTICIPANTS: An average of 8917 (5019-11 656) schoolchildren 3 to 18 years of age were selected using stratified systematic cluster sampling or by probability proportional to size sampling. METHODS: All participants underwent complete ophthalmic evaluations. Three drops of 0.5% tropicamide were used to obtain the cycloplegic refractive status of each participant. Questionnaires were used to acquire participant data from the 1995, 2005, 2010, and 2016 surveys. MAIN OUTCOME MEASURES: Prevalence of myopia (spherical equivalence of ≤-0.25 diopter [D]) and high myopia (≤-6.0 D) was assessed. Multivariate analyses of risk factors were conducted. RESULTS: The prevalence of myopia among all age groups increased steadily. From 1983 through 2017, the weighted prevalence increased from 5.37% (95% confidence interval [CI], 3.50%-7.23%) to 25.41% (95% CI, 21.27%-29.55%) for 7-year-olds (P = 0.001 for trend) and from 30.66% (95% CI, 26.89%-34.43%) to 76.67% (95% CI, 72.94%-80.40%) for 12-year-olds (P = 0.001 for trend). The prevalence of high myopia also increased from 1.39% (95% CI, 0.43%-2.35%) to 4.26% (95% CI, 3.35%-5.17%) for 12-year-olds (P = 0.008 for trend) and from 4.37% (95% CI, 2.91%-5.82%) to 15.36% (95% CI, 13.78%-16.94%) for 15-year-olds (P = 0.039 for trend). In both the 2005 and 2016 survey samples, children who spent less than 180 minutes daily on near-work activities showed significantly lower risks for myopia developing (<60 minutes: odds ratio [OR], 0.48 and 0.56; 60-180 minutes: OR, 0.69 and 0.67). In the 2016 survey, spending more than 60 minutes daily on electronic devices was associated significantly with both myopia and high myopia (OR, 2.43 and 2.31). CONCLUSIONS: The prevalence of myopia among schoolchildren increased rapidly from 1983 through 2017 in Taiwan. The major risk factors are older age and time spent on near-work activities. Use of electronic devices increased the amount of time spent on near-work and may increase the risk of developing myopia.

Exploring a peptidomimetic approach of N-cadherin in modulating fibroblast growth factor receptor signaling for corneal endothelial regeneration.

Endothelial rejection and a critical shortage of corneal transplants present an unmet medical need in corneal regeneration research area. Although basic fibroblast growth factor (bFGF) is a potent mitogenic factor for corneal ex vivo expansion, it is also a morphogen eliciting unfavorable endothelial-mesenchymal transition (EnMT) of corneal endothelial cells. A pharmacological reagent that retains the beneficial proliferative effect while lacking the EnMT effect of bFGF would be of great potential in corneal regeneration. In present study, we demonstrated that bFGF not only activated the canonical fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase pathway, but also further upregulated matrix metalloproteinase activity to cleave N-cadherin into N-terminus and C-terminus fragments, which activated the classical FGFR1 tyrosine kinase pathway and a cryptic ß-catenin pathway to affect corneal proliferation and EnMT, respectively. We generated the synthetic peptides resembling a critical motif in the ectodomain of N-cadherin and found these peptides enhanced downstream proliferative signaling of FGFR1 but without seemingly EnMT effect. The potential of these peptides can be demonstrated on both ex vivo cell culture and in vivo rat cryo-injury model. Our study indicated this peptidomimetic approach of N-cadherin can stimulate corneal regeneration and offer a promising therapeutic option to treat corneal endothelial dysfunction.

Clinical characteristics of glaucoma patients with disc hemorrhage in different locations.

PURPOSE: To compare the clinical characteristics and outcomes of eyes with unilateral disc hemorrhage (DH) in different locations. METHODS: This was a retrospective cohort study. DHs were classified by locations: the superior, superotemporal, inferotemporal, or inferior sectors of optic disc were classified as the susceptible area, while other sectors were defined as the less susceptible area. Structural and functional outcomes were analyzed by the Humphrey field analyzer and spectral domain optical coherence tomography. RESULTS: Forty-three eyes with DHs in the susceptible area were less myopic and had more peripapillary-type DH, larger cup-to-disc ratio, cup volume, and disc area. Thirty-three eyes with DHs in the less susceptible area had less association with RNFL defects, greater tilted ratio, and less torsion of the disc. Follow-up revealed that the change in sectoral RNFL (µm) thickness was significantly greater for DHs in the susceptible area within one year (- 6.0 ± 14.0 vs. 0.7 ± 13.0, p = 0.035) and two years (- 10.0 ± 17.4 vs. - 1.1 ± 7.6, p = 0.012), while the change in average RNFL thickness was not different. Eyes with DHs in the susceptible area had faster MD deterioration (dB/year) than those in the less susceptible area within four years (- 0.32 ± 0.51 vs. - 0.05 ± 0.45, p = 0.047). A total of 16.9% of eyes, all in the susceptible area, had localized VF progression at DH corresponding area. CONCLUSION: Disc hemorrhage in the superotemporal and inferotemporal regions had more subsequent structural and functional deterioration compared with the eyes with DHs in the temporal quadrant and nasal area.

Insidious-onset, non-wheezing carteolol-induced asthma in an atopic patient without asthma history.

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.