Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study.

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

OCTA biomarkers in adults aged 50 and above: a prospective and cross-sectional community-based study.

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods: OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results: A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates. Conclusions: Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias. Translational Relevance: Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

A Novel Tumor Staging System Incorporating Tumor Regression Grade (TRG) With Lymph Node Status (ypN-Category) Results in Better Prognostication Than ypTNM Stage Groups After Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aims at constructing a staging system incorporating tumor regression grade and ypN-category (TRG-N) in patients with neoadjuvant therapy before esophagectomy. It is hypothesized that this would prognosticate better than the current American Joint Committee on Cancer (AJCC) postneoadjuvant therapy (ypTNM) stage groups. BACKGROUND: Conventional pathological T-category is defined by the depth of invasion, and may lose prognostic relevance after neoadjuvant therapy. TRG defines treatment response by the degree of tumor regression, and when combined with ypN-category may be more prognostic than AJCC postneoadjuvant therapy (ypTNM) stage groups. METHODS: A training cohort of 210 patients with esophageal squamous cell carcinoma and who had had neoadjuvant therapy before esophagectomy were studied. A validation cohort comprised 107 patients from another hospital. Resected esophagi were assessed by ypT-category and TRG, the latter assigned according to the Becker 4-tier system. These categories were grouped with ypN-category into a TRG-N system. Patients' survival was compared between the current AJCC postneoadjuvant therapy (ypTNM) stage groups and this TRG-N system. RESULTS: In the training cohort, 5-year survival rates according to ypTNM stage I, II, IIIA, IIIB, and IVA were 53%, 39.4%, 47%, 18.3%, and 0%, respectively. For TRG-N stages I, II, III, and IV, the respective figures were 59.6%, 43.5%, 23.8%, and 15.6%. TRG-N stage showed better fit in survival than ypTNM stage groups, indicated by lower Akaike Information Criteria (AIC) and Bayesian Information Criterion values. Similar results were found in the validation cohort. Multivariate analysis showed that TRG-N stage ( P =0.02), age ( P =0.006), and sex ( P =0.005) were independent prognostic factors. CONCLUSION: TRG-N stage shows better prognostication than the AJCC postneoadjuvant therapy (ypTNM) stage groups.

Improving Outcome of Superior Mediastinal Lymph Node Dissection During Esophagectomy: A Novel Approach Combining Continuous and Intermittent Recurrent Laryngeal Nerve Monitoring.

OBJECTIVE: This study aimed at demonstrating the effects and learning curve of utilizing combined intermittent and continuous recurrent laryngeal nerve (RLN) monitoring for lymphadenectomy during esophagectomy. BACKGROUND: RLN lymphadenectomy is oncologically important but is technically demanding. Vocal cord (VC) palsy as a result from RLN injury, carries significant morbidities. METHODS: This is a retrospective study of consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent transthoracic esophagectomy from 2010 to 2020. Combined nerve monitoring (CNM) included: CNM which involved a periodic stimulating left vagal electrode and intermittent nerve monitoring which utilized a stimulating probe to identify the RLNs. The integrity of the RLNs was assessed both intermittently and continuously. This technique was introduced in 2014. Patients were divided into "before CNM" and "CNM" groups. The primary outcome was the difference in number of RLN lymph nodes harvested and VC palsy rate. Learning curves were demonstrated by cumulative sum (CUSUM) analysis. RESULTS: Two hundred and fifty-five patients were included with 157 patients in "CNM" group. The mean number of RLN lymph nodes harvested was significantly higher (4.31 vs 0.45, P < 0.0001) for the "CNM" group. VC palsy rates were significantly lower (17.8% vs 32.7%, P = 0.007). There was an initial increase in VC palsy rate, peaked at around 46 cases. The increase in lymph nodes harvested above the mean plateaued at around 96 cases. CONCLUSIONS: CNM helped improve bilateral RLN lymphadenectomy. Lymph node harvesting was increased with reduction of VC palsy after a learning curve.

Transcervical Transtracheal Resection of Cervical Esophageal Smooth Muscle Tumor.

Cervical esophageal smooth muscle tumors are traditionally resected via lateral transcervical with or without video-assisted thoracoscopic approaches. Exposure is frequently limited, however, with risks of recurrent laryngeal nerve and posterior tracheal wall injury and jeopardization of cervical tracheal and cervical esophageal blood supply. We herein describe an anterior transcervical transtracheal approach to counter some of the aforementioned problems and avoid morbidities associated with thoracoscopic surgery when resecting smooth muscle tumors arising from the cervical esophagus.

Computed tomography-based deep-learning prediction of neoadjuvant chemoradiotherapy treatment response in esophageal squamous cell carcinoma.

BACKGROUND: Deep learning is promising to predict treatment response. We aimed to evaluate and validate the predictive performance of the CT-based model using deep learning features for predicting pathologic complete response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Patients were retrospectively enrolled between April 2007 and December 2018 from two institutions. We extracted deep learning features of six pre-trained convolutional neural networks, respectively, from pretreatment CT images in the training cohort (n = 161). Support vector machine was adopted as the classifier. Validation was performed in an external testing cohort (n = 70). We assessed the performance using the area under the receiver operating characteristics curve (AUC) and selected an optimal model, which was compared with a radiomics model developed from the training cohort. A clinical model consisting of clinical factors only was also built for baseline comparison. We further conducted a radiogenomics analysis using gene expression profiles to reveal underlying biology associated with radiological prediction. RESULTS: The optimal model with features extracted from ResNet50 achieved an AUC and accuracy of 0.805 (95% CI, 0.696-0.913) and 77.1% (65.6%-86.3%) in the testing cohort, compared with 0.725 (0.605-0.846)) and 67.1% (54.9%-77.9%) for the radiomics model. All the radiological models showed better predictive performance than the clinical model. Radiogenomics analysis suggested a potential association mainly with WNT signaling pathway and tumor microenvironment. CONCLUSIONS: The novel and noninvasive deep learning approach could provide efficient and accurate prediction of treatment response to nCRT in ESCC, and benefit clinical decision making of therapeutic strategy.

Incorporating Optical Coherence Tomography Macula Scans Enhances Cost-effectiveness of Fundus Photography-Based Screening for Diabetic Macular Edema.

OBJECTIVE: To compare four screening strategies for diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: Patients attending diabetic retinopathy screening were recruited and received macular optical coherence tomography (OCT), in addition to visual acuity (VA) and fundus photography (FP) assessments, as part of the standard protocol. Two retina specialists provided the reference grading by independently assessing each subject's screened data for DME. The current standard protocol (strategy A) was compared for sensitivity, specificity, quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER) with three alternative candidate protocols using a simulation model with the same subjects. In strategy B, macular hemorrhage or microaneurysm on FP were removed as surrogate markers for possible DME. Strategy C used best-corrected instead of habitual/pinhole VA and added central subfield thickness (CST) >290 µm on OCT in suspected cases as a confirmation marker for possible DME. Strategy D used CST >290 µm OCT in all subjects as a surrogate marker for suspected DME. RESULTS: We recruited 2,277 subjects (mean age 62.80 ± 11.75 years, 43.7% male). The sensitivities and specificities were 40.95% and 86.60%, 22.86% and 95.63%, 32.38% and 100%, and 74.47% and 98.34% for strategies A, B, C, and D, respectively. The costs (in U.S. dollars) of each QALY gained for strategies A, B, C, and D were $7,447.50, $8,428.70, $5,992.30, and $4,113.50, respectively. CONCLUSIONS: The high false-positive rate of the current protocol generates unnecessary referrals, which are inconvenient for patients and costly for society. Incorporating universal OCT for screening DME can reduce false-positive results by eightfold, while improving sensitivity and long-term cost-effectiveness.

Possible Modifying Effect of Hemoglobin A1c on Genetic Susceptibility to Severe Diabetic Retinopathy in Patients With Type 2 Diabetes.

Purpose: Glycemic control has been recognized as an important modifiable risk factor for diabetic retinopathy (DR). Whether hemoglobin A1c (HbA1c), as an indicator of glycemic control, could modify the genetic susceptibility to severe DR remains to be investigated. This study aimed to investigate whether HbA1c could modulate the genetic susceptibility to severe DR in Chinese patients with type 2 diabetes. Methods: A total of 3,093 Chinese individuals with type 2 diabetes were included in the cross-sectional case-control study: 1,051 with sight-threatening DR (STDR) and 2,042 without STDR. Sixty-nine top-ranked single nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies were examined for their associations with STDR and proliferative DR as a subgroup analysis. SNPs showing suggestive associations with DR were examined in the stratified analysis by dichotomized HbA1c (<7% vs. ≥7%). An interaction analysis was performed by including an interaction term of SNP × HbA1c in the regression model. Results: Four SNPs showed suggestive associations with STDR. In the stratified analysis, patients with adequate glycemic control (HbA1c <7%) had a 42% lower risk of STDR for carrying each additional protective C allele of COL5A1 rs59126004 (P = 1.76 × 10-4; odds ratio, 0.58; 95% confidence interval, 0.44-0.77). rs59126004 demonstrated a significant interaction with dichotomized HbA1c on the risk of STDR (Pinteraction = 1.733 × 10-3). In the subgroup analysis for proliferative DR, the protective effect of rs59126004 was even more pronouncedly demonstrated (P = 8.35 × 10-5; odds ratio, 0.37; 95% confidence interval, 0.22-0.60) and it showed similar interactions with dichotomized HbA1c (Pinteraction = 1.729 × 10-3). Conclusions: Our data provided evidence for possible interactions between HbA1c and COL5A1 rs59126004 on the risk of severe DR. These findings may provide new insight into the pathophysiologic mechanism of DR.

Neoadjuvant Chemoradiotherapy Using Cisplatin and 5-Fluorouracil (PF) Versus Carboplatin and Paclitaxel (CROSS Regimen) for Esophageal Squamous Cell Carcinoma (ESCC): A Propensity Score-matched Study.

OBJECTIVE: This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC. BACKGROUND: PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed. METHODS: This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis ("CROSS Eligibility") was performed based on tumor length, cT-stage, cM-stage, age, and performance status. RESULTS: One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For "CROSS Eligible subgroup," the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093). CONCLUSIONS: There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.

Prevalence and Causes of Visual Impairment and Blindness among Adult Chinese in Hong Kong - The Hong Kong Eye Study.

PURPOSE: To investigate the prevalence, associations, and causes of visual impairment and blindness in the adult population of Hong Kong. METHODS: This cross-sectional population-based study included 2018 (870, 43% male) randomly selected adults with a mean age 52 ± 16 years (range 18-90 years) in Hong Kong. Each participant underwent comprehensive ophthalmic examinations. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) of each eye was recorded. Prevalence of visual impairment and blindness was calculated using both World Health Organization (WHO) and United States (US) definitions, based on BCVA and PVA. RESULTS: Visual acuity measurements were available for 1952 (96.8%) participants. The prevalence of visual impairment, based on BCVA value, using WHO and US definition, was 1.0 ± 0.1% and 2.7 ± 0.4%, respectively. The prevalence of visual impairment, based on PVA value, was 5.1 ± 0.5% and 14.0 ± 0.8%, using WHO and US definition, respectively. Multivariate analysis demonstrated the presence of visual impairment (PVA, WHO definition) increased significantly with older age (odds ratio 1.039, P < .001) and thinner central cornea thickness (odds ratio 0.994, P = .014), but not significantly associated with other socioeconomic, systemic or ocular parameters after adjusting for age and central corneal thickness. Under-correction of refractive error was the most common reason for presenting visual impairment. Causes of impaired BCVA were cataract (37%), age-related macular degeneration (26%), diabetic macular edema (11%), glaucoma (11%), epiretinal membrane (5%), and unknown (11%). CONCLUSION: The prevalence of visual impairment in Hong Kong increased significantly with older age and thinner central corneal thickness. The major causes for impairment were under-correction of refractive error, cataract, and age-related macular degeneration.

Treatment of large, chronic and persistent macular hole with internal limiting membrane transposition and tuck technique.

BACKGROUND: Large, chronic full thickness macular holes which failed previous treatments are difficult to manage and even left untreated due to poor prognosis. A retrospective review of consecutive cases with chronic (at least 1 year) full thickness macular holes and internal limiting membrane (ILM) free flap transposition with tuck technique, after previously failed vitrectomy. METHODS: This was a retrospective and interventional study conducted in a single centre by a single surgeon. Patients with full thickness macular hole for at least 1 year and at least one previously failed vitrectomy with ILM peeling were recruited. A 25G vitrectomy with ILM free flap transposition was done without assistance of PFCL, viscoelastic or autologous blood. The free flap was manually tucked into the macular hole free space and gas fluid exchange was performed with 20% SF6 as tamponade. The patients were postured prone for 2 weeks postoperatively. Best corrected visual acuity, macular hole duration, previous surgeries, optical coherence tomography (OCT) appearance, hole size and closure rate were recorded. RESULTS: 8 consecutive patients were included from May 2016 to Feb 2018. Transposition surgery was performed an average of 1481 days (SD 1096) after diagnosis of macular hole and average of 1226 days (SD 1242) after first vitrectomy. Macular hole mean size was 821 µm (SD 361.3), preoperative VA was logMAR 1.038 (SD 0.19), postoperative VA was logMAR 0.69 (SD 0.19) at 3 months. There were 1.13 lines gained and a significant improvement of logMAR 0.33 (p = 0.0084) at 6 months. Hole closure was seen in 7 out of 8 eyes (87.5%). The OCT with failed closure showed ILM flap within a flat hole, however no overlying neurosensory layers was seen. The duration from diagnosis to surgery was 2349 days in this case. CONCLUSION: Free flap ILM transposition tuck without the use of additional intraoperative tamponade is an effective technique in treating large chronic macular holes with previously failed primary macular hole surgeries.Trial registration (IRB of the Hong Kong University and Hospital Authority Hong Kong West Cluster, ref UW19-440), June 17, 2019.

Exophthalmometry values in the Hong Kong Chinese adult population from a population-based study.

This study aims to establish the range of exophthalmometry values (EV) in the adult Hong Kong (HK) Chinese population, its relationship with various anthropometric parameters, and to compare it with the EV in different ethnic groups.About 1485 adult HK Chinese were drawn from a random sample from the community-based FAMILY Cohort. Participants were interviewed, and comprehensive ophthalmological assessments were conducted. EV was measured using the Hertel's exophthalmometer.EV of both eyes from 630 male (42.4%) and 855 female (57.6%) participants, mean age 54 ±â€Š17.2 and 52 ±â€Š16 respectively were analyzed. The mean EV were found to be 15.3 ±â€Š2.8 mm in the right eye, 15.2 ±â€Š2.9 mm in the left eye for men and 14.4 ±â€Š2.7 mm in the right eye, 14.3 ±â€Š2.7 mm in the left eye for women. There were no differences in the EV between right and left eyes (P > .05). Men had significantly higher EV than women (P < .05) and age was found to be negatively correlated to EV (P < .05). Body height (r = 0.20), weight (r = 0.25), waist (r = 0.11), hip circumference (r = 0.15), body mass index (r = 0.17), interpupillary distance (r = 0.54), and axial length (AL) (r = 0.20) were all found to have statistically significant positive correlations with EV (P < .01). Spherical equivalent was found to have statistically significant negative correlation with EV (P < .01).Our study provides normative data on EV in the HK Chinese population. Height, weight, interpupillary distance, waist, hip circumference, and AL had positive correlations with EV. Spherical equivalent had negative correlation with EV. There was no significant difference in EV between the right and left eye. Age and gender had significant effect on EV.

Macular Vessel Density Measured With Optical Coherence Tomography Angiography and Its Associations in a Large Population-Based Study.

Purpose: We investigate macular perfusion and the systemic and ocular associations in a population-based setting. Methods: In this cross-sectional study, 2018 adults residing in Hong Kong underwent detailed ophthalmic examinations after consenting to participate. Macular perfusion was measured with optical coherence tomography angiography (OCTA) using the split-spectrum amplitude decorrelation angiography algorithm. The parafoveal flow index and vessel area density were quantified using automated custom-built software. Results: Of the 2018 participants, the OCTA measurements were available for 1940, and 1631 (84.1%) had good quality scans. The right eyes of these 1631 participants (43.1% men) were included for final analysis. Mean age was 49.8 years (range, 18-92 years). Mean global macular vessel density was 47.3% and 55.1% for the superficial and deep retinal layers, respectively. In multivariate analysis, lower superficial vessel density remained significantly associated with lower signal strength index (SSI; P < 0.001, standardized ß = 0.607) and male sex (P < 0.001, ß = 0.162), and borderline associated with older age (P = 0.09, ß = -0.045) and longer axial length (AL; P = 0.09, ß = -0.037), while lower deep layer vessel density was significantly associated with lower SSI (P < 0.001, standardized ß = 0.667), longer AL (P < 0.001, ß = -0.097), and higher creatinine (P < 0.001, ß = -0.072). Conclusions: This large population-based study provided normative OCTA data of macular vessel density and demonstrated that a lower superficial retinal vessel density was significantly associated with lower SSI and male sex, while a lower deep layer retinal vessel density was significantly associated with lower SSI, longer AL, and higher level of creatinine. These associations must be considered when interpreting clinical quantitative OCTA data.

Corneal Biomechanics Using a Scheimpflug-Based Noncontact Device in Normal-Tension Glaucoma and Healthy Controls.

PURPOSE: To determine if a novel biomechanical parameter, corneal applanation velocity, as measured by the Corvis ST, is associated with a diagnosis of normal-tension glaucoma (NTG). DESIGN: Prospective, cross-sectional study. METHODS: Study and control subjects were recruited from the ophthalmology clinic of a university teaching hospital in Hong Kong over an 8-week period in 2013. A total of 80 eyes with NTG diagnosis and 155 healthy eyes randomly selected to be in the control group were included in the final analysis. All subjects underwent corneal biomechanical testing with the Oculus Corvis ST non-contact tonometer. Logistic regression analysis adjusted for age and central corneal thickness was conducted to assess the relationship between inward and outward applanation velocity and the risk of NTG. Secondary outcome variables included corneal applanation time, length, amplitude, and highest concavity. RESULTS: Inward applanation velocity was faster in the NTG eyes (0.15 ± 0.02 m/s) than in the control eyes (0.14 ± 0.02 m/s) (P = 0.016). The odds ratio for a 0.01 m/s increase in inward applanation velocity when comparing NTG eyes with control eyes adjusted for age and central corneal thickness was 1.15 (95% confidence interval, 1.03-1.30) (P = 0.016). There was no evidence that outward applanation velocity or any secondary corneal biomechanical variable differed between the NTG and control eyes. CONCLUSIONS: Normal-tension glaucoma eyes demonstrated a small, statistically significant faster corneal inward applanation velocity than normal control eyes.

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report.

BACKGROUND: Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors. CASE PRESENTATION: We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance. CONCLUSIONS: This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of "idiopathic" optic neuritis in the Chinese population.

Injectable silicone rubber for ocular implantation after evisceration.

OBJECTIVE: To investigate the usefulness of addition type liquid silicone rubber (ATLSR) as injectable implant after evisceration to maintain the eyeball volume in an animal experiment. METHODS: Twelve adult New Zealand white rabbits were included. One eye of each rabbit was randomly selected for evisceration with the fellow eye as control. ATLSR was injected to fill the eyeball socket after evisceration. In vivo observation and photographs were performed up to 24 weeks post-op. Two rabbits were sacrificed respectively at post-operative week 1, 2, 4, 8, 12 and 24. After enucleation, the vertical, horizontal and sagittal diameters of the experimental eyeballs were measured and compared with the control eyes. Histopathological studies were performed to evaluate signs of inflammation. RESULTS: Cornea remained clear throughout the observation period despite mild epithelial edema and neovascularization. Compared to the control eyes, the experimental eyes were significantly smaller in vertical diameter (17.00±1.17 vs. 17.54±1.11 mm, P<0.001), but larger in sagittal diameter (16.85±1.48 vs. 16.40±1.38 mm, P = 0.008), and had no significant difference in horizontal diameter (17.49±1.53 vs. 17.64±1.21 mm, P = 0.34). Postoperative inflammation was observed at one week after surgery, which peaked at 2-3 weeks, then regressed gradually. At week 12 and week 24, most of the inflammatory cells disappeared with some residual plasma cells and eosinophils. CONCLUSION: Injectable addition type silicon rubber may be a good choice for ocular implantation after evisceration, maintaining eyeball volume and cosmetically satisfactory when compared to the fellow eye. Spontaneous regression of inflammation implied good biocompatibility for at least 24 weeks.

Repeated intraocular crystallization of ganciclovir in one eye after bilateral intravitreal injections: a case report.

BACKGROUND: Cytomegalovirus (CMV) retinitis is an opportunistic infection that primarily affects immunocompromised individuals. Intravitreal ganciclovir injection monotherapy or in combination with systemic anti-CMV therapy are effective treatments for CMV retinitis. Crystallization of ganciclovir after intravitreal injection is extremely rare. Only two cases had been reported in literature. Crystallization in only one eye after bilateral injections had not been reported before. We hereby report a case of intraocular ganciclovir crystallization in one eye after bilateral intravitreal injections, and repeated crystallization in the same eye after repeated injections. CASE PRESENTATION: A 79-year-old patient had bilateral cytomegalovirus retinitis and received bilateral intravitreal ganciclovir injections of 2.5 mg in 0.05 ml sterile water. Fundus examination after injection showed formation of needle-shaped, golden-yellow crystals in the vitreous of right eye but not in left eye. The crystals dissolved spontaneously. Repeated bilateral intravitreal ganciclovir injections 4 days later resulted in repeated crystallization of ganciclovir in right eye but not in left eye. The crystals dissolved spontaneously and completely after 5 minutes. Visual acuity remained unchanged and intraocular pressure was normal. CONCLUSIONS: Intraocular ganciclovir crystallization could occur after intravitreal injections. It is important to perform fundus examination after injection. The crystals may dissolve rapidly and vitrectomy may not be necessary. Our case suggested intraocular ganciclovir crystallization is an idiosyncratic phenomenon, subjects to distinctive intraocular environment which could be different between two eyes of the same patient. The susceptible intraocular environment could be persistent leading to repeated crystallization.

Peroral Endoscopic Myotomy with EndoFLIP and Double-Endoscope: Novel Techniques for Achalasia in Pediatric Population.

BACKGROUND: Experience of peroral endoscopic myotomy (POEM) for treatment of achalasia in pediatric population is limited with varying techniques in different centers. The accurate extent of submucosal tunneling into the gastric cardia and the adequacy of myotomy are the important determining factors to success of POEM. A majority of studies in pediatric population have described using submucosal dye injection for assessing the adequacy of myotomy, however, this is a rather crude and inaccurate method. We herein describe the first case of pediatric achalasia managed with POEM incorporated with novel combined techniques using EndoFLIP® (Endoluminal Functional Lumen Imaging Probe) and double endoscope. METHODS: Esophagogastric junction (EGJ) was identified with a gastroscope. Before POEM, EndoFLIP showed EGJ distensibility index of 1.7 mm2/mmHg. Submucosal tunnel was created from the mucosal entry site at midesophagus down and ∼3 cm beyond the EGJ. Anterior myotomy cutting the circular muscle layer while preserving the longitudinal muscle was performed for 8 cm. Double-endoscope technique was used to confirm the adequacy of myotomy by inserting a smaller endoscope through nostril into stomach and observing the transillumination of the first endoscope at the end of submucosal tunnel. After POEM, repeat EndoFLIP measurements revealed increased distensibility index to 6.0 mm2/mmHg. Endoscopic examination at the end of the procedure showed widely patent EGJ. RESULTS: Eckardt symptoms score improved from 9 to 0. At 7 month after POEM, esophagoscopy showed widely open EGJ with no esophagitis, and high-resolution esophageal manometry revealed normalized lower esophageal sphincter pressure and resting tone. CONCLUSIONS: We introduced the intraoperative use of EndoFLIP system that allows real-time assessment of EGJ distensibility and immediate treatment effect evaluation. Incorporation of double-endoscope POEM was also first described in our pediatric patient for ensuring complete gastric myotomy. From our experiences, POEM for achalasia in pediatric population appears to have encouraging results similar to adult patients.