Systemic resilience and COVID-19: lessons from Taiwan.

In May 2021, Taiwan experienced its first COVID-19 surge. Up until then, this geopolitically vulnerable nation had contained the pandemic well. The situation seemed dire at the peak of the surge, however, within two months, the crisis had been resolved. Aside from technical measures such as border control and mandated social distancing, other underlying systemic factors- including an accreditation-strengthened and digitalized healthcare system, government resourcefulness, and continuously adaptive strategies- were crucial to Taiwan's success, and have demonstrated the importance of systemic resilience in terms of navigating the pandemic.

CONSEQUENCES OF LAPSES IN TREATMENT WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN ROUTINE CLINICAL PRACTICE.

PURPOSE: Evaluating outcomes in patients receiving intravitreal antivascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration whom experience a lapse in treatment. METHODS: A retrospective chart review evaluating 3,304 patients ≥18 years who experienced treatment lapses ≥3 months compared with control counterparts. Demographic information, macular thickness as measured by central subfield thickness, and visual acuity were collected at baseline, the first postlapse appointment, and at 3, 6, and 12 months after the lapse for the study group. RESULTS: Lapse (n = 241) and control patients (n = 241) had similar baseline visual acuity and central subfield thickness (Early Treatment Diabetic Retinopathy Study: 58.9 ± 20.2 [20/63] vs. 59.2 ± 20.1 [20/63]; central subfield thickness: 252.4 ± 63.2 µm vs. 259.8 ± 66.2 µm, P = 0.21). Analysis revealed that lapse patients experienced a significant increase in central subfield thickness after lapse when compared with controls (279.4 ± 86.9 µm vs. 253.7 ± 65.9 µm, P < 0.01), which normalized on resumption of treatment (259.1 ± 79 µm vs. 246.8 ± 57.6 µm, P = 0.06). Study patients also experienced loss in the visual acuity after lapse when compared with controls (52.9 ± 23.6 Early Treatment Diabetic Retinopathy Study [20/100] vs. 59.9 ± 20.8 [20/63] Early Treatment Diabetic Retinopathy Study, P < 0.01) that did not recover through 12 months of follow-up. CONCLUSION: Patients with neovascular age-related macular degeneration who have lapses in care are at risk for poorer outcomes. Although macular thickness normalizes on resumption of treatment, their decline in the visual acuity does not recover.

Artificial Intelligence-Assisted Early Detection of Retinitis Pigmentosa - the Most Common Inherited Retinal Degeneration.

The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs.

The prevalence of olfactory and gustatory dysfunction in covid-19 - A systematic review.

OBJECTIVES: Loss of smell or taste are early symptoms of COVID-19. Given the high asymptomatic rate of COVID-19, as well as unreliable temperature checking and contact history taking, it is important to understand the role of olfactory and gustatory dysfunction (OGD) in the diagnosis of COVID-19. The aim of this study is to determine how initial symptoms of OGD can be used to screen patients for COVID-19 laboratory testing. METHODS: We followed recommendations from the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) statement to conduct this systematic review study. We used OGD-related key words to search for literature published between January 1, 2020 and September 30, 2020 on Pubmed, Ovid Medline databases. We estimated the prevalence of OGD and compared it with that of other OGD-related symptoms. The weighted summary proportion under the fixed and random effects model was assessed using MedCalc statistical software. Whenever there was heterogeneity, a random effects model was selected. Publication bias was assessed by funnel plot asymmetry and Egger's regression test. RESULTS: A total of 25 articles (evidence level III:5; IV:20) were identified and reviewed. Data synthesis of 19 articles revealed that the pooled prevalence of olfactory dysfunction in COVID-19 is 53.56% (range 5.6-100%, 95% CI 40.25-66.61%). The pooled prevalence of gustatory dysfunction in COVID-19 is 43.93% (range 1.5-85.18%, 95% CI 28.72-59.74%), just behind fever (62.22%, range 18.18-95.83%, 95% CI 54.82-69.33%), cough (64.74%, range 38.89-87.5%, 95% CI 57.97-71.22%), and fatigue (56.74%, range 6.25-93.62%, 95% CI 32.53-79.35%). The prevalence of gustatory dysfunction in subgroup with objective evaluation is lower than those without (9.91% vs. 49.21%, relive risk 2.82, p<0.001). CONCLUSION: Our updated systematic review attests that OGD is an important early symptom of COVID-19 infection. Screening for OGD should be further emphasized to prioritize patients for laboratory test.

Fluctuations in macular thickness in patients with diabetic macular oedema treated with anti-vascular endothelial growth factor agents.

PURPOSE: To evaluate retinal thickness fluctuations in patients with diabetic macular oedema (DMO) treated with anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Visual acuity (VA) and central subfield thickness (CST) were collected at baseline, 3, 6, 9 and 12 months. Retinal thickness fluctuation was quantified by standard deviation (SD) of CST across 12 months. A mixed effects regression model evaluated the relationship between CST SD and VA at 12 months. Multiple linear regression analysis was performed to investigate predictors of CST SD. RESULTS: Mean baseline and 12-month VAs were 63.5 ± 15.7 and 69.0 ± 13.8 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (change = +5.1 ± 16.1 letters, p < 0.001). Mean baseline and 12-month CSTs were 396.9 ± 109.7 and 337.7 ± 100.7 µm (change = -59.2 ± 114.8 µm, p < 0.001). Retinal thickness variability across the first 12 months was 59.4 ± 43.6 µm. Stratification of patient eyes by CST SD demonstrated 9.7 letters difference in 12-month VA between first and fourth quartiles. Significant predictors of CST SD include baseline CST, injection type, laser treatment, and DR stage. CONCLUSIONS: Larger retinal thickness fluctuations are associated with poorer visual outcomes in eyes with DMO treated with anti-VEGF injections. Retinal thickness variability may be an important prognostic biomarker for DMO patients.

Clinical manifestations and genetic analysis of a family with neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominantly inherited disease with slow, yet potentially life-threatening progression. OBJECTIVE: We describe the clinical manifestations and genetic profile of a family with NF2. METHODS: We enrolled a 16-member family with NF2. We collected clinical examinations and imaging information. Genetic analysis was conducted through multiplex ligation-dependent probe amplification (MLPA). The SALSA MLPA probemix P044-B2 NF2 kit was used to detect genetic variations in genomic upstream and 17 exons of the NF2 gene. RESULTS: The most common clinical manifestation was hearing impairment (37.5%), followed by tinnitus (18.8%). Four participants had vestibular schwannoma: 2 were bilateral and 2 unilateral, and tumor size ranged from 86.3 to 5064 mm3. A weak correlation between hearing impairment and tumor size was observed. Genetic analysis revealed that the DNA dosages of exons 9, 10, and 11 of the NF2 gene in 3 diseased family members (participants #3, #5, and #11) were higher than those in the controls. However, we could not detect an indicative abnormal DNA dosage of NF2 in participant #6 despite such a dosage being considered a diagnostic indicator of NF2. CONCLUSIONS: Hearing impairment was the most common clinical manifestation in this family. The NF2 gene is a gene of interest that warrants familial genetic screening.

Genetic characteristics and epidemiology of inherited retinal degeneration in Taiwan.

Inherited retinal degenerations (IRDs) are a group of phenotypically and genotypically heterogeneous disorders with substantial socioeconomic impact. In this cohort study, we tried to address the genetic characteristics and epidemiology of IRDs in Taiwan. Totally, 312 families with IRDs were identified and recruited and genetic testing was performed via probe capture-based NGS targeting 212 IRD-related genes. Statistical analysis was based on the proband of each affected family. Disease-causing genotypes were identified in 178 families (57.1%). ABCA4 variants were the most common cause of disease in this cohort (27 families, 15.2%), whereas CYP4V2 variants were the most common cause for the single phenotype-Bietti's crystalline dystrophy (12 families, 3.8%). Some variants such as ABCA4:c.1804C>T, CYP4V2:c.802-8_810delinsGC, and EYS:c6416G>A were population-specific disease-causing hotspots. Probands affected by ABCA4, RPGR, RP1L1, and CEP290 sought medical help earlier while patients affected by EYS and CYP4V2 visited our clinic at an older age. To evaluate the representativeness of our cohort in the genetic epidemiology of IRDs in Taiwan, our demographic data were compared with that of the total IRD population in Taiwan, obtained from the National Health Insurance Research Database. This is currently the largest-scale, comprehensive study investigating the genetic characteristics and epidemiology of IRD in Taiwan. These data could help patients and caregivers to adopt precision genomic medicine and novel gene therapies in near future.

Three-dimensional, virtual reality vestibular rehabilitation for chronic imbalance problem caused by Ménière's disease: a pilot study.

PURPOSES: The purpose of this study was to evaluate a three-dimensional, virtual reality system for vestibular rehabilitation in patients with intractable Ménière's disease and chronic vestibular dysfunction. METHODS: We included 70 patients (36 for study, 34 as control) with a chronic imbalance problem caused by uncompensated Ménière's disease. The virtual reality vestibular rehabilitation comprised four training tasks (modified Cawthorne-Cooksey exercises: eye, head, extension, and coordination exercises) performed in six training sessions (in 4 weeks). Measurements of the task scores and balance parameters obtained at the baseline and after final training sessions were compared. RESULTS: A significant improvement was observed in extension and coordination scores. Patients in the early stages of Ménière's disease had a significantly greater improvement in the center of gravity sway and trajectory excursion in the mediolateral direction than did patients in the late stages of Ménière's disease. Mild functional disability attributable to Ménière's disease was a predictor of improvement in the statokinesigram and maximum trajectory excursion in the anteroposterior direction after rehabilitation. The control group showed no significant improvement in almost all parameters. CONCLUSION: Virtual reality vestibular rehabilitation may be useful in patients with Ménière's disease, particular those in the early stages or having mild functional disability. Implication for rehabilitation Chronic imbalance caused by uncompensated Ménière's disease is an indication for vestibular rehabilitation. The interactive virtual reality video game, when integrated into vestibular rehabilitation exercise protocol, may assist patients who have mild disability Ménière's disease and who cannot benefit from treatment with drugs or surgery. The initial data from this study support the applicability of three-dimensional virtual reality technology in vestibular rehabilitation programs. The technology gives professionals a new tool to guide patients for vestibular rehabilitation exercises through three-dimensional virtual reality video game playing. The virtual reality vestibular exercise game can provide patients a step-wise, interactive, dynamic, three-dimensional, and interesting rehabilitation environment.