Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions.

Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial-mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.

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.

Reciprocity of Cell Mechanics with Extracellular Stimuli: Emerging Opportunities for Translational Medicine.

Human cells encounter dynamic mechanical cues in healthy and diseased tissues, which regulate their molecular and biophysical phenotype, including intracellular mechanics as well as force generation. Recent developments in bio/nanomaterials and microfluidics permit exquisitely sensitive measurements of cell mechanics, as well as spatiotemporal control over external mechanical stimuli to regulate cell behavior. In this review, the mechanobiology of cells interacting bidirectionally with their surrounding microenvironment, and the potential relevance for translational medicine are considered. Key fundamental concepts underlying the mechanics of living cells as well as the extracelluar matrix are first introduced. Then the authors consider case studies based on 1) microfluidic measurements of nonadherent cell deformability, 2) cell migration on micro/nano-topographies, 3) traction measurements of cells in three-dimensional (3D) matrix, 4) mechanical programming of organoid morphogenesis, as well as 5) active mechanical stimuli for potential therapeutics. These examples highlight the promise of disease diagnosis using mechanical measurements, a systems-level understanding linking molecular with biophysical phenotype, as well as therapies based on mechanical perturbations. This review concludes with a critical discussion of these emerging technologies and future directions at the interface of engineering, biology, and medicine.

Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians: Pooled Analysis from the Asian Eye Epidemiology Consortium.

PURPOSE: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. DESIGN: Cross-sectional pooled analysis. PARTICIPANTS: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. METHODS: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. MAIN OUTCOME MEASURES: Average RNFL thickness (in micrometers) and rim area (in square millimeters). RESULTS: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (ß values range, 7.31-12.76 µm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 µm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 µm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 µm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, ß = -2.70), diabetes (ß = -0.72), higher IOP (per 1 mmHg, ß = -0.07), more myopic SE (per diopter, ß = -1.13), cardiovascular disease (ß = -0.94), and hypertension (ß = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (ß = -0.019), higher IOP (ß = -0.010), and more myopic SE (ß = -0.025) were associated with smaller rim area (all P < 0.001). CONCLUSIONS: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.

Somatic mutations in collagens are associated with a distinct tumor environment and overall survival in gastric cancer.

BACKGROUND: Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. METHODS: We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. RESULTS: In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. CONCLUSIONS: These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.

Motility-limited aggregation of mammary epithelial cells into fractal-like clusters.

Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested, fractal-like clusters at low density in reduced epidermal growth factor (EGF). These clusters exhibit a branched architecture with a fractal dimension of [Formula: see text], reminiscent of diffusion-limited aggregation of nonliving colloidal particles. First, cells display diminished motility in reduced EGF, which permits irreversible adhesion upon cell-cell contact. Subsequently, leader cells emerge that guide collectively migrating strands and connect clusters into space-filling networks. Thus, this living system exhibits gelation-like arrest at low cell densities, analogous to the glass-like arrest of epithelial monolayers at high cell densities. We quantitatively capture these behaviors with a jamming-like phase diagram based on local cell density and EGF. These individual to collective transitions represent an intriguing link between living and nonliving systems, with potential relevance for epithelial morphogenesis into branched architectures.

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.

Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis.

TOPIC: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045. CLINICAL RELEVANCE: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population. METHODS: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019. RESULTS: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians. DISCUSSION: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.

The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems.

The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression. Video Abstract.

Topological data analysis of collective and individual epithelial cells using persistent homology of loops.

Interacting, self-propelled particles such as epithelial cells can dynamically self-organize into complex multicellular patterns, which are challenging to classify without a priori information. Classically, different phases and phase transitions have been described based on local ordering, which may not capture structural features at larger length scales. Instead, topological data analysis (TDA) determines the stability of spatial connectivity at varying length scales (i.e. persistent homology), and can compare different particle configurations based on the "cost" of reorganizing one configuration into another. Here, we demonstrate a topology-based machine learning approach for unsupervised profiling of individual and collective phases based on large-scale loops. We show that these topological loops (i.e. dimension 1 homology) are robust to variations in particle number and density, particularly in comparison to connected components (i.e. dimension 0 homology). We use TDA to map out phase diagrams for simulated particles with varying adhesion and propulsion, at constant population size as well as when proliferation is permitted. Next, we use this approach to profile our recent experiments on the clustering of epithelial cells in varying growth factor conditions, which are compared to our simulations. Finally, we characterize the robustness of this approach at varying length scales, with sparse sampling, and over time. Overall, we envision TDA will be broadly applicable as a model-agnostic approach to analyze active systems with varying population size, from cytoskeletal motors to motile cells to flocking or swarming animals.

Nanotechnology: emerging tools for biology and medicine.

Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine.

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 Pattern of Geographic Atrophy in Asia: The Asian Eye Epidemiology Consortium.

PURPOSE: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). DESIGN: Cross-sectional meta-analyses. PARTICIPANTS: A total of 97 213 individuals aged 40 years and older. METHODS: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. MAIN OUTCOME MEASURES: Prevalence of GA per 1000 persons. RESULTS: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005). CONCLUSIONS: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

ONE-YEAR RESULTS OF HALF- VERSUS STANDARD-DOSE PHOTODYNAMIC THERAPY COMBINED WITH RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To explore the efficacy of half-dose verteporfin photodynamic therapy (hd-PDT) and standard-dose photodynamic therapy (sd-PDT), when combined with ranibizumab in the treatment of polypoidal choroidal vasculopathy. METHODS: Subjects were allocated to either the hd-PDT arm or the sd-PDT arm. All subjects received an injection of ranibizumab and PDT treatment (dosage according to allocation) at baseline. Subjects were followed up monthly for 12 months, and re-treatment were given at each visit if criteria were met. RESULTS: There were 26 subjects in the hd-PDT arm and 32 in the sd-PDT arm. Overall mean age was 69.3 ± 9.4 years. Baseline demographics and ocular features did not differ significantly between the two arms. Improvement in vision and reduction in central retinal thickness were similar between the two arms. When presenting, visual acuity was better than 20/50 (logarithm of the minimum angle of resolution 0.4), or when there were three or less polyps angiogram, those treated with hd-PDT tended to perform better than those treated with sd-PDT. CONCLUSION: In general, hd-PDT was able to produce similar results as sd-PDT. Subgroup analysis revealed superior results with hd-PDT when baseline vision was 20/50 or better, or when there were three or less polyps on indocyanine green angiography.

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.

Early epithelial complications of accelerated trans-epithelial corneal crosslinking in treatment of keratoconus: a case series.

BACKGROUND: To report a case series of early postoperative complications following combined accelerated corneal crosslinking (CXL) and trans-epithelial technique in keratoconus. CASE PRESENTATIONS: Eleven eyes underwent accelerated trans-epithelial CXL (18 mW/cm2 for 5 min). Seven eyes (64%) developed complications in the first week postoperatively. Five eyes had large epithelial defects, and two eyes were complicated with diffuse punctate epithelial erosions. Early transient stromal haze was seen in eyes with epithelial complications. Anterior segment optical coherence tomography showed a faint demarcation line in six eyes (55%) with epithelial complications. CONCLUSION: A significant number of eyes developed epithelial complications shortly after combined accelerated trans-epithelial CXL, which defeated the benefits of leaving the epithelium intact.

A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

PURPOSE: To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. METHODS: All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. RESULTS: A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s = 0.437, p = 0.003). CONCLUSION: The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

Serial Spectral-Domain Optical Coherence Tomography Findings in Acute Retinal Pigment Epitheliitis and the Correlation to Visual Acuity.

PURPOSE: To evaluate the features of acute retinal pigment epitheliitis (ARPE) at onset and in the course of recovery by serial spectral-domain optical coherence tomography (SD OCT) and the correlation to visual acuity (VA). DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive patients with ARPE. METHODS: A review of medical records was performed. MAIN OUTCOME MEASURES: Integrity of SD OCT retinal bands at onset and in the course of disease, time required to achieve each retinal band restoration, corresponding VA change, and final VA. RESULTS: Four patients were included. Initial SD OCT showed a dome-shaped hyper-reflective lesion at the photoreceptor outer segment layer disrupting the ellipsoid zone (EZ) and interdigitation zone (IZ) (100%). In the early phase, there was also upward displacement of the external limiting membrane (ELM) and mild transient thickening of the retinal pigment epithelium (RPE)/Bruch's complex (Bc). Acute retinal pigment epitheliitis resolved in a sequence of (1) a decrease in height of SD OCT hyper-reflective lesion and the upwardly displaced ELM returning to its normal position with irregularity; (2) complete disappearance of the hyper-reflective lesion; (3) restoration of ELM; (4) restoration of EZ; and (5) restoration of IZ. The average time to restore ELM, EZ, and IZ was 4.3±5.2, 7.3±7.2, and 12.5±12.4 weeks, respectively, and the corresponding logarithm of the minimum angles of resolution (logMAR) VAs were 0.24±0.23, 0.09±0.07, and 0.05±0.06, respectively. Visual acuity improved when IZ was restored. CONCLUSIONS: Early SD OCT revealed an inflammatory lesion in the photoreceptor outer segment layer displacing ELM. The RPE was involved only mildly and transiently. Recovery occurred in a sequence of ELM, EZ, and IZ restoration, and VA improved when the IZ was restored. These features suggested that the IZ (i.e., the contact between photoreceptors and RPE) is the primary site of inflammation in ARPE.