Using Smartphone Chatbot for Postoperative Care after Intravitreal Injection during COVID-19 Period: A Retrospective Cohort Study.

BACKGROUND: During COVID-19 pandemic period, it was difficult for the patients regular and scheduled follow-up in outpatient department, especially when lock-down. However, early detection of patients with initial infection or other serious conditions after ocular surgeries, such as intravitreous injection (IVI) for age-related macular degeneration (AMD). OBJECTIVE: We accessed a postoperative care chatbot system (PCCS) in smartphone for patients to self-report postoperative symptoms/signs with an instant bidirectional feedback system. METHODS: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patient to report and grade six ocular symptoms/signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days postoperatively to assess their symptoms/signs per day after receiving an alert. The data automatically collected using a cloud computer system judged the grade and sent messages to medical staff for further medical assistance. User's satisfaction questionnaire was collected on the 7th day. RESULTS: One hundred and eighty-five patients participated in this study. There were 26 reports (3.03%) of symptom grade deterioration (increased blurred vision, eye swelling, nausea, and floater/flash) in 12 patients (6.5%). No gender difference for the earlier medical consultation. One case occurred endophthalmitis and improved after 2 times prompt IVI antibiotics. 87% of patients were satisfied or very satisfied to communicate their symptoms instantly with the app, willing to use it again and considered it could improve quality of care. The incidence of earlier medical consultation is 3.8% (7/185) and the incidence of endophthalmitis is 0.5% (1/185). CONCLUSIONS: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing early medical consultation without gender differences in AMD patients who receiving intravitreal injections. It achieves satisfactory response from patients.

Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report.

PURPOSE: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5. DESIGN: Randomized, double-masked extended trial. PARTICIPANTS: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups. MAIN OUTCOMES MEASURES: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5. RESULTS: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively. CONCLUSIONS: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Prevalence of Congenital Color Vision Deficiency in Southern Taiwan and Detection of Female Carriers by Visual Pigment Gene Analysis.

This study aimed to investigate the prevalence of color vision deficiencies (CVDs) and determine whether carriers could be detected by analyzing the visual pigment genes. Materials and Methods: The data of students who underwent routine CVD screening using the Ishihara color test in Kaohsiung, Southern Taiwan were analyzed. Furthermore, the DNA samples of 80 randomly selected females and four obligate carriers were analyzed. The most upstream genes, downstream genes, and the most downstream genes in the red/green pigment gene arrays were amplified separately using polymerase chain reaction (PCR), and exon 5 of each gene was analyzed. The prevalence of congenital red-green CVD in this study was 3.46% in males and 0.14% in females. The PCR analysis of the first gene, downstream gene, and last gene revealed normal patterns in 73 normal cases. Seven unusual patterns were detected in two proton carriers and five deutan carriers. Among the randomly selected females, 8.8% (7/80) were CVD carriers. The prevalence of CVD among male Taiwanese students in this study was 3.46%. Female carriers of congenital CVD can be identified by molecular analysis of the visual pigment genes. The proportion of CVD carriers among the randomly selected females was 8.8%, which was slightly higher than expected and further studies are warranted.

Treatment of Myopia with Atropine 0.125% Once Every Night Compared with Atropine 0.125% Every Other Night: A Pilot Study.

(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: -0.29 ± 0.44 vs. -0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = -0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies.

The Prevalence of Optical Coherence Tomography Artifacts in High Myopia and its Influence on Glaucoma Diagnosis.

PRCIS: Optical coherence tomography (OCT) artifacts occur much more frequently in highly myopic eyes compared with non-highly myopic eyes. A longer axial length is predictive of having OCT artifacts. PURPOSE: To investigate the types and prevalence of artifacts on OCT scans in patients with and without high myopia. MATERIALS AND METHODS: Patients were divided into 4 groups based on whether they had glaucoma and/or high myopia. All peripapillary retinal nerve fiber layer (RNFL) scan images were individually inspected for the presence of artifacts. RESULTS: Two hundred twenty-six patients were enrolled. The prevalence of OCT artifacts was 18.6% in non-high myopes and 51.9% in high myopes ( P <0.001). Outer RNFL border misidentification was the most common type of artifact for non-high myopes, whereas retinal pathology-related artifact was the most common in high myopes. Univariable regression analysis showed that a longer axial length [odds ratio (OR) 1.815, P <0.001], a higher pattern standard deviation (OR 1.194, P <0.001), and thinner RNFL (OR 0.947, P <0.001) were predictive factors for the presence of OCT artifacts. The diagnostic capability of global RNFL thickness before and after manual correction of segmentation errors did not differ for both non-high myopes [area under the receiver operating curve 0.915-0.913 ( P =0.955)] and high myopes [area under the receiver operating curve 0.906-0.917 ( P =0.806)]. CONCLUSION: The prevalence of OCT artifacts was the highest in patients with both high myopia and glaucoma. The most common type of OCT artifact is different for non-high myopes and high myopes. Physicians need to be aware of a higher likelihood of OCT artifacts, particularly in those with a longer axial length, worse visual field, and thinner RNFL thickness.

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia.

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.

BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting. METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 µm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 µm in CRT. RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: - 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (- 127.6 ± 104.2 µm and - 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (- 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005). CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Ultraviolet A at levels experienced outdoors suppresses transforming growth factor-beta signaling and collagen production in human scleral fibroblasts.

Previous studies have highlighted the importance of outdoor time in reducing the risk of myopia progression. Although ultraviolet A (UVA) radiation dominates in terms of energy with respect to the UV radiation reaching the Earth's surface, its effects on the exposed anterior sclera have not been well studied. This study was designed to investigate the UVA-induced biological effects at peak sunlight levels in human scleral fibroblasts (HSFs). Using next-generation sequencing (NGS), we analyzed the differentially expressed genes (DEGs) in UVA-treated and normal HSFs. Further, we then identified the functions and key regulators of the DEGs using bioinformatics analysis, and verified the effects of UVA on gene and protein expression in HSFs using real-time PCR, western blotting, and immunofluorescence imaging. The highest level of solar UVA (365 nm) was 3.4 ± 0.18 (mW/cm2). The results from the functional analysis of the DEGs were related to structural changes in the extracellular matrix (ECM) and protein metabolism. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were predicted to be potential upstream regulators, associated with ECM organization. Exposure to a single wavelength of UVA (365 nm, 3 mW/cm2) for 1 h for 5 consecutive days induced the downregulation of the mRNA of ECM genes including COL1A1, COL3A1, COL5A1, VCAN and collagen I protein in HSF. UVA downregulated Smad3 protein and reduced TGF-ß-induced collagen I protein production following UVA exposure in HSF. In conclusion, high UVA exposure reduces TGF-ß signaling and collagen I production by modulating Smad levels in HSF. The effects of overexposure to high-intensity UVA on myopia control require further investigations.

Punicalagin Attenuates LPS-Induced Inflammation and ROS Production in Microglia by Inhibiting the MAPK/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation.

Purpose: Neurodegenerative diseases are associated with neuroinflammation along with activation of microglia and oxidative stress, but currently lack effective treatments. Punicalagin is a natural bio-sourced product that exhibits anti-inflammatory effects on several chronic diseases; however, the anti-inflammatory and anti-oxidative effects on microglia have not been well examined. This study aimed to investigate the effects of punicalagin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and the production of ROS using murine microglia BV2 cells. Methods: BV2 cells were pre-treated with punicalagin following LPS treatment to induce inflammation. The secretion of NO and PGE2 was analyzed by Griess reagent and ELISA respectively, while the expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were analyzed using Western blotting, the production of IL-6 was measured by ELISA, and the activity of NF-κB was detected using promoter reporter assay. To examine whether punicalagin affects NLRP3 inflammasome activation, BV2 cells were stimulated with LPS and then treated with ATP or nigericin. The secretion of IL-1ß was measured by ELISA. The expressions of NLRP3 inflammasome-related proteins and phospho IκBα/IκBα were analyzed using Western blotting. The production of intracellular and mitochondrial ROS was analyzed by flow cytometry. Results: Our results showed that punicalagin attenuated inflammation with reduction of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1ß, and reduction of IL-6 led to inhibition of STAT3 phosphorylation by LPS-induced BV2 cells. Punicalagin also suppressed the ERK, JNK, and p38 phosphorylation, attenuated NF-κB activity, inhibited the activation of the NLRP3 inflammasome, and reduced the production of intracellular and mitochondrial ROS by LPS-induced BV2 cells. Conclusion: Our results demonstrated that punicalagin attenuated LPS-induced inflammation through suppressing the expression of iNOS and COX-2, inhibited the activation of MAPK/NF-κB signaling pathway and NLRP3 inflammasome, and reduced the production of ROS in microglia, suggesting that punicalagin might have the potential in treating neurodegenerative diseases.

Outcomes and eye care knowledge in rhegmatogenous retinal detachment patients with a history of laser refractive surgery for myopia.

Purpose: To investigate the surgical outcomes and eye care knowledge of patients with rhegmatogenous retinal detachment (RRD) who had previously undergone laser refractive surgery (LRS) for myopia in a myopia epidemic area. Methods: This retrospective study included patients with primary RRD who underwent surgery and had a history of LRS for myopia at a tertiary medical center. Data were reviewed from medical charts to analyse the surgical outcomes. Questions about eye care knowledge and attitude toward myopia and LRS were obtained. Results: A total of 774 patients underwent RRD surgery, among whom 341 (44%) had myopia > -3 dioptres, 66% of whom had high myopia. Thirty eyes of 26 patients had a history of LRS for myopia. The mean age of patients with a history of LRS was significantly lower than that of those without a history of LRS (45.7 ± 2.9 years vs. 53.8 ± 1.0, p < 0.001). The mean pre-LRS spherical equivalent was -8.66 ± 0.92 (range: -3.00--12.00) dioptres. In more than half the patients (n = 15, 57.7%), the interval between LRS and RRD was more than 10 years. The primary retinal reattachment rate was only 60%, whereas the final retinal reattachment rate was 93%. The mean final visual acuity (VA) improved from a 20/286 to 20/105 (p = 0.006). Linear mixed model analysis showed factors of male sex and macular detachment were significant with poor visual outcome (p = 0.046 and 0.008) Eye care knowledge obtained from the 19 RRD patients with history of LRS, 47% of patients (9/19) mistakenly thought that LRS could cure myopia and its complications, and 63% of patients were less willing to visit an ophthalmologist because uncorrected VA improvement after LRS. Eighty-four percent thought that proper knowledge and more education about LRS and myopia for the public are important. Conclusion: In the RRD patients with a history of LRS for myopia, their age was relative younger. Male sex and macular detachment were associated with poor visual outcome. More education with proper knowledge of LRS, myopia and RRD is recommended for the patients to prevent or early detect the occurrence of RRD.

Optical coherence tomography and imaging biomarkers as outcome predictors in diabetic macular edema treated with dexamethasone implant.

In this retrospective, multicenter study, we determined the predictive value of imaging biomarkers in diabetic macular edema (DME) outcomes following dexamethasone (DEX) implant(s). Sixty-seven eyes of 47 patients' best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography (OCT) before and after intravitreal DEX implants were evaluated. Baseline imaging biomarkers were graded using fundus photography and OCT, and the predictive value of biomarkers for significant treatment effects at six months was analyzed. Six months after 2.0 ± 0.8 (mean ± SD) DEX implants, 35 (52%) and 16 (24%) eyes had CFT reduction ≥ 10% from baseline and decreased to < 300 µm, respectively. BCVA improved ≥ 3 lines in 15 (22%) and remained stable in 38 (57%) eyes. At six months, eyes with severe intraretinal cyst (IRC), abundant hyperreflective dots (HRD), and moderate or severe hard exudate had a significantly higher chance of CFT reduction ≥ 10%. Eyes with abundant HRD at baseline and those underwent three DEX implants were more likely to achieve CFT < 300 µm. Eyes with DME and severe IRC, abundant HRD, or moderate-to-severe hard exudate at baseline were more likely to show a significant reduction in CFT six months after DEX implant.

Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography.

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (ß = -14.43, p = 0.008; ß = -0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control.

Combination Therapy with Intravitreal Triamcinolone Acetonide and Oral Levodopa for the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Pilot Study.

Purpose: To determine the clinical effectiveness of combination therapy with intravitreal injection of triamcinolone acetonide (IVITA) and oral levodopa in eyes affected by nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Longitudinal study involving 45 eyes of 45 patients with NAION who were evaluated within 14 days of NAION onset. The treatment group received an IVITA 4 mg/0.1 mL followed by 25 mg carbidopa/100 mg levodopa (Sinemet 25-100) 3 times daily for 12 weeks and the control group was untreated. Best-corrected visual acuity (BCVA) converted to logarithmic minimum angle of resolution (logMAR), visual field (VF) grades based on automated or Goldman perimetry, and mean retinal nerve fiber layer (RNFL) thickness measured on optical coherence tomography were assessed at the initial visit, 1, 3, and 6 months after NAION attack. Results: At the first visit and 6 months after NAION onset, the mean logMAR BCVA in the treatment group was significantly better than the control group (P < 0.05). BCVA was not significantly different between onset and the 6-month visit for both the control and the treatment group; however, the change in BCVA after 6 months was significantly greater in the treatment group compared with the control group (P = 0.007). Concomitant systemic disease, the changes in VF grades, and RNFL thickness from initial to 6 months after NAION onset were not significantly different between 2 groups. Conclusions: Combination therapy with IVITA and oral levodopa/carbidopa appears to be effective in the treatment of recent-onset NAION.

Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan.

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient's disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts' opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2-3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3-4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

One-year outcomes of the treat-and-extend regimen using aflibercept for the treatment of diabetic macular edema.

BACKGROUND: Optimal regimen using intravitreal aflibercept injections for diabetic macular edema (DME) in clinical practice remains to be elucidated. The purpose of this study is to evaluate a treat-and-extend (TAE) approach using intravitreal aflibercept in participants with center-involved DME. METHODS: A 52-week open-label, prospective, multicenter, interventional study was conducted between August 2015 and November 2017 in Taiwan. Adults with diabetes mellitus and center-involved DME who have best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (CRT) >300 µm were included. Participants received five monthly loading doses of 2 mg intravitreal aflibercept, followed by a TAE regimen with a four-week increment/decrement interval over 48 weeks; the maximum interval was 12 weeks. Main outcomes included changes in BCVA and CRT from baseline to week 52, additional anatomical outcomes, and treatment burden parameters. RESULTS: Forty-five participants with mean (SD) age of 63.7 (8.3) years were analyzed. At baseline, mean (SD) BCVA and CRT were 58.3 (11.9) letters and 434.4 (116.8) µm, respectively. Changes from baseline in BCVA and CRT were +8.3 (9.3) letters and -138.2 (150.0) µm (both p < 0.001) at week 52, respectively. In addition, 22% (10/45) of patients gained ≥15 letters, 14% (6/44) of participants achieved ≥2-level improvement in diabetic retinopathy severity, and 51% (23/45) demonstrated dry retina at week 52 compared with 13% (6/45) at baseline. In total, 87% (39/45) of patients reached disease stability, entering TAE at week 20. Subsequently, 89% (40/45) of patients reached maximum interval at week 52. Mean (SD) number of injections was 7.7 (1.5) over a period of 52 weeks. CONCLUSION: This straightforward and practical TAE regimen using intravitreal aflibercept injections resulted in favorable clinical outcomes with minimal treatment burden for DME at week 52.

Mutation survey in Taiwanese patients with Stickler syndrome.

PURPOSE: The purpose of this study was to identify gene mutation and phenotype correlations in a cohort of Taiwanese patients with Stickler syndrome. MATERIALS AND METHODS: Patients clinically diagnosed with Stickler syndrome or suspected Stickler syndrome were enrolled. DNA was extracted from venous blood samples. For the targeted next-generation sequencing (NGS) approach, specific primers were designed for all COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 exons and flanking intron sequences. RESULTS: Twenty-three patients from 12 families were enrolled in this study. The myopia power in these 23 cases (35 eyes) ranged from -4.625 to -25.625 D, with a median of -10.00 D. Four patients had retinal detachment. Fourteen patients had a cleft palate. These 23 patients and 13 healthy controls were enrolled in the NGS study. Three families had significant single nucleotide variants (SNVs) in COL2A1. The mutation rates in this survey were 25% (3/12 families) and 35% (8/23 cases). The SNV of family #1, located at exon 27, c.1753G >T, p. Gly585Val, was novel and has not yet been reported in the ClinVar database. Families #10 and #11 had the same SNV, located in exon 33, c.2101C >T, p. Arg701X. Both variants were classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. CONCLUSION: Genetic mutations in COL2A1 were found in 25% of Taiwanese families with Stickler syndrome. One novel variant was identified using NGS, which expanded the COL2A1 mutation spectrum. Molecular genetic analysis is helpful to confirm the clinical diagnosis of patients with suspected Stickler syndrome.

Stepwise low concentration atropine for myopic control: a 10-year cohort study.

The aim of this study was to analyze changes in refraction and evaluate the variables in school children who received atropine as myopic control for 10 years. Low-concentration atropine (0.05%) was prescribed initially, and the dose was increased in a stepwise manner if rapid myopic progression (≥ 0.5D per half year) was noted during the regular follow-up visit. 23 children with a mean age of 6.96 ± 1.07 years were included. The initial spherical equivalent was - 1.25 ± 0.84 D. The overall mean myopic progression was - 0.30 ± 0.27 D/year. Younger initial age, female, higher initial spherical equivalent and the need of higher concentration of atropine were found to be risk factors for myopic progression in multivariate mixed-effect analysis (p = 0.013, 0.017, 0.024 and 0.014). Children who kept using a lower concentration of atropine (≤ 0.1%) tended to have slower myopic progression throughout the 10-year course than those who shifted to higher concentrations (> 0.1%) (p ≤ 0.001). Stepwise low concentration of atropine might be effective for long-term myopic control in school students. Those who had poor response to lower concentration of atropine may have the risk of faster progression, even with high concentration of atropine. Additional or alternative treatment might be considered.

Early Age of the First Myopic Spectacle Prescription, as an Indicator of Early Onset of Myopia, Is a Risk Factor for High Myopia in Adulthood.

PURPOSE: The present study investigated the risk factors for high myopia in adulthood, with a focus on the age at which children wore their first spectacles. METHODS: Adults aged between 20 and 45 years were invited to complete a questionnaire about age, sex, current refractive error, high myopia in parents, early onset of myopia presented by the age of the first myopic spectacle prescription, refractive power of the first spectacles, and life habits at different educational stages. The associations between these factors and high myopia in adulthood were then evaluated and analyzed. RESULTS: In total, 331 participants were enrolled. Their average refractive error was -4.03 diopters, and high myopia was noted in 27.5% of the study participants. Only 3.3% of participants had fathers with high myopia, while 6.0% had mothers with high myopia. The participants received their first myopic spectacle prescription at a mean age of 13.35 years, with a mean refractive error of -1.63 diopters. The significant risk factors for developing high myopia in adult life were earlier age of the first spectacles prescribed (p < 0.001), higher refractive power of the first spectacles (p < 0.001), mother with high myopia (p=0.015), and after-school class attendance in senior high school (p=0.018). Those who wore their first spectacles at <9 years of age were more predisposed to high myopia than those who did so at ≧13 years, with an odds ratio of 24.9. CONCLUSION: The present study shows that earlier onset of myopia, which is presented by the age of the first myopic spectacle prescription, higher myopic refraction of the first spectacles, mothers with high myopia, and after-school class attendance in senior high school are risk factors for high myopia in adulthood. It suggests that delaying the onset of myopia in children is important for the prevention of high myopia in later life.