Alpha-1-B glycoprotein (A1BG) inhibits sterol-binding and export by CRISP2.

Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in various processes, including sperm maturation and cancer progression. They are mostly secreted glycoproteins and share a unique conserved CAP domain. The precise mode of action of these proteins, however, has remained elusive. Saccharomyces cerevisiae expresses three members of this protein family, which bind sterols in vitro and promote sterol secretion from cells. This sterol-binding and export function of yeast Pry proteins is conserved in the mammalian CRISP proteins and other CAP superfamily members. CRISP3 is an abundant protein of the human seminal plasma and interacts with alpha-1-B glycoprotein (A1BG), a human plasma glycoprotein that is upregulated in different types of cancers. Here we examined whether the interaction between CRISP proteins and A1BG affects the sterol-binding function of CAP family members. Co-expression of A1BG with CAP proteins abolished their sterol export function in yeast and their interaction inhibits sterol-binding in vitro. We map the interaction between A1BG and CRISP2 to the third of five repeated immunoglobulin-like (Ig) domains within A1BG. Interestingly, the interaction between A1BG and CRISP2 requires magnesium, suggesting that coordination of Mg2+ by the highly conserved tetrad residues within the CAP domain is essential for a stable interaction between the two proteins. The observation that A1BG modulates the sterol-binding function of CRISP2, has potential implications for the role of A1BG and related Ig domain containing proteins in cancer progression and the toxicity of reptile venoms containing CRISP proteins.

RSK2 inactivation cooperates with AXIN1 inactivation or ß-catenin activation to promote hepatocarcinogenesis.

BACKGROUND & AIMS: Recurrent somatic mutations of the RPS6KA3 gene encoding for the serine/threonine kinase RSK2 were identified in hepatocellular carcinomas (HCCs), suggesting its tumour-suppressive function. Our goal was to demonstrate the tumour suppressor role of RSK2 in the liver and investigate the functional consequences of its inactivation. METHODS: We analysed a series of 1,151 human HCCs for RSK2 mutations and 20 other driver genetic alterations. We then modelled RSK2 inactivation in mice in various mutational contexts recapitulating or not those naturally found in human HCC, using transgenic mice and liver-specific carcinogens. These models were monitored for liver tumour appearance and subjected to phenotypic and transcriptomic analyses. Functional consequences of RSK2 rescue were also investigated in a human RSK2-deficient HCC cell line. RESULTS: RSK2-inactivating mutations are specific to human HCC and frequently co-occur with AXIN1-inactivating or ß-catenin-activating mutations. Modelling of these co-occurrences in mice showed a cooperative effect in promoting liver tumours with transcriptomic profiles recapitulating those of human HCCs. By contrast, there was no cooperation in liver tumour induction between RSK2 loss and BRAF-activating mutations chemically induced by diethylnitrosamine. In human liver cancer cells, we also showed that RSK2 inactivation confers some dependency to the activation of RAS/MAPK signalling that can be targeted by MEK inhibitors. CONCLUSIONS: Our study demonstrates the tumour suppressor role of RSK2 and its specific synergistic effect in hepatocarcinogenesis when its loss of function is specifically combined with AXIN1 inactivation or ß-catenin activation. Furthermore, we identified the RAS/MAPK pathway as a potential therapeutic target for RSK2-inactivated liver tumours. IMPACT AND IMPLICATIONS: This study demonstrated the tumour suppressor role of RSK2 in the liver and showed that its inactivation specifically synergises with AXIN1 inactivation or ß-catenin activation to promote the development of HCC with similar transcriptomic profiles as found in humans. Furthermore, this study highlights that activation of the RAS/MAPK pathway is one of the key signalling pathways mediating the oncogenic effect of RSK2 inactivation that can be targeted with already available anti-MEK therapies.

Correlation of Body Mass Index with Anthropometric and Biochemical Parameters Among Polycystic Ovary Syndrome Phenotypes.

This was a prospective observational study, conducted at a tertiary care health centre in Rajasthan. A total of 68 women with PCOS (Rotterdam criteria) attending OPD at Department of Obstetrics and Gynecology qualified as per inclusion and exclusion criteria were included in the study. Each participant was examined for anthropometric and biochemical parameters. The largest phenotypic group was phenotype A, (41.17%); followed by B (26.47%); C (20.58%), and D (P + O) phenotypes (11.76%). Hyperandrogenic phenotypes (A, B, C), had significantly higher prevalence of deranged serum glucose (fasting and postprandial), lipid profile and serum TSH than normoandrogenic phenotype D. BMI was strongly correlated with anthropometric (p < 0.001) and biochemical parameters (p < 0.05) in phenotype A among four phenotypes of PCOS. Phenotype A was the most common form of PCOS and a strong correlation of BMI with waist circumference (WC), dyslipidemia and Sub-clinical hypothyroidism (SCH) was observed in women of this phenotype of PCOS. These results indicate that phenotype A is at increased risk of CVD and diabetes and phenotype D has least metabolic risks.

Epigallocatechin gallate is a potent inhibitor of cystathionine beta-synthase: Structure-activity relationship and mechanism of action.

Epigallocatechin gallate (EGCG) is the main bioactive component of green tea. Through screening of a small library of natural compounds, we discovered that EGCG inhibits cystathionine ß-synthase (CBS), a major H2S-generating enzyme. Here we characterize EGCG's mechanism of action in the context of CBS-derived H2S production. In the current project, biochemical, pharmacological and cell biology approaches were used to characterize the effect of EGCG on CBS in cellular models of cancer and Down syndrome (DS). The results show that EGCG binds to CBS and inhibits H2S-producing CBS activity almost 30-times more efficiently than the canonical cystathionine formation (IC50 0.12 versus 3.3 µM). Through screening structural analogs and building blocks, we identified that gallate moiety of EGCG represents the pharmacophore responsible for CBS inhibition. EGCG is a mixed-mode, CBS-specific inhibitor with no effect on the other two major enzymatic sources of H2S, CSE and 3-MST. Unlike the prototypical CBS inhibitor aminooxyacetate, EGCG does not bind the catalytic cofactor of CBS pyridoxal-5'-phosphate. Molecular modeling suggests that EGCG blocks a substrate access channel to pyridoxal-5'-phosphate. EGCG inhibits cellular H2S production in HCT-116 colon cancer cells and in DS fibroblasts. It also exerts effects that are consistent with the functional role of CBS in these cells: in HCT-116 cells it decreases, while in DS cells it improves viability and proliferation. In conclusion, EGCG is a potent inhibitor of CBS-derived H2S production. This effect may contribute to its pharmacological effects in various pathophysiological conditions.

BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA.

BACKGROUND & AIMS: DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) that occurs in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered. METHODS: A series of 151 liver tumors including 126 HCC, 15 FLC, and 10 mixed-FLC/HCC were analyzed by RNAseq and whole-genome- or whole-exome sequencing. Western blots were performed to validate genomic discoveries. Results were validated using the TCGA database. RESULTS: Most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of 17 tumors, which all had mutations or translocations inactivating BAP1, the gene encoding BRCA1-associated protein-1. Like FLC, BAP1-HCC were significantly enriched in females, patients with a lack of chronic liver disease, and fibrotic tumors compared to non-BAP1 HCC. However, patients were older and had a poorer prognosis than those with FLC. BAP1 tumors were immune hot, showed progenitor features and did not show DNAJB1-PRKACA fusion, while almost none of these tumors had mutations in CTNNB1, TP53 and TERT promoter. In contrast, 80% of the BAP1 tumors showed a chromosome gain of PRKACA at 19p13, combined with a loss of PRKAR2A (coding for the inhibitory regulatory subunit of PKA) at 3p21, leading to a high PRKACA/PRKAR2A ratio at the mRNA and protein levels. CONCLUSION: We have characterized a subgroup of BAP1-driven HCC with fibrolamellar-like features and a dysregulation of the PKA pathway, which could be at the root of the clinical and histological similarities between BAP1 tumors and DNAJB1-PRKACA FLCs. LAY SUMMARY: Herein, we have defined a homogeneous subgroup of hepatocellular carcinomas in which the BAP1 gene is inactivated. This leads to the development of cancers with features similar to those of fibrolamellar carcinoma. These tumors more frequently develop in females without chronic liver disease or cirrhosis. The presence of PKA activation and T cell infiltrates suggest that these tumors could be treated with PKA inhibitors or immunomodulators.

Corneal densitometry changes post-CXL for keratoconus: Comparative evaluation of epithelium-off, contact lens-assisted, and transepithelial techniques.

PURPOSE: To evaluate changes in corneal backscattering after collagen cross-linking (CXL) for progressive keratoconus and compare its course with different techniques - standard epithelium-off CXL (SCXL), contact lens-assisted CXL (CACXL), and transepithelial CXL (TECXL). SETTING: Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. DESIGN: Retrospective comparative study. METHODS: Ninety-four eyes (SCXL: 47, CACXL: 30, and TECXL: 17) were compared. Corneal haze was quantified using Scheimpflug tomography, pre- and post-CXL at 1, 3, 6, and 12 months. RESULTS: The baseline mean density score of the central anterior stromal layer was 16.14 ± 7.07, 15.85 ± 7.89 and 15.89 ± 7.21 in SCXL, CACXL, and TECXL groups, respectively (P 0.93). After SCXL, the score increased to 28.83 and 31.34 at 1 and 3 months, respectively (both P < 0.001) and dropped at 6 months (28.66, P < 0.001) and 12 months (23.72, P 0.003). Post-CACXL, the mean densitometry peaked at 3 months (20.35, P 0.14) and returned toward baseline at 6 months (18.82, P 0.15). After TECXL, it increased slightly at 1 month (18.47, P 0.17), decreased at 3 months (14.88, P 0.7), and plateaued over 1 year. No correlation with visual acuity was seen. CONCLUSION: Corneal haze increased significantly after SCXL, peaking at 3 months, declining over 6-12 months, and returning to baseline at 12 months. In contrast, post-TECXL and -CACXL, there was an insignificant increase in anterior corneal haze, which returned to baseline within 3-6 months.

Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma.

Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

Mutational signature, cancer driver genes mutations and transcriptomic subgroups predict hepatoblastoma survival.

BACKGROUND: Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease. METHODS: All the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated. RESULTS: High-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0-208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with 'Liver Progenitor' (p = 0.00049, p < 0.0001) and 'Immune Cold' (p = 0.0011, p < 0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p = 0.018, p = 0.001), mutations in rare cancer driver genes (p = 0.0039, p = 0.0017) and embryonal predominant histological type (p = 0.0013, p = 0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic 'Immune Cold' and Liver Progenitor' as a predictor of survival independent of the clinical features. CONCLUSIONS: Response to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features.

Association of dietary intake with micronutrient deficiency in Indian school children: a cross-sectional study.

Adequate nutrition is necessary during childhood and early adolescence for adequate growth and development. Hence, the objective of the study was to assess the association between dietary intake and blood levels of minerals (calcium, iron, zinc, and selenium) and vitamins (folate, vitamin B12, vitamin A, and vitamin D) in urban school going children aged 6-16 years in India, in a multicentric cross-sectional study. Participants were enrolled from randomly selected schools in ten cities. Three-day food intake data was collected using a 24-h dietary recall method. The intake was dichotomised into adequate and inadequate. Blood samples were collected to assess levels of micronutrients. From April 2019 to February 2020, 2428 participants (50⋅2 % females) were recruited from 60 schools. Inadequate intake for calcium was in 93⋅4 % (246⋅5 ± 149⋅4 mg), iron 86⋅5 % (7⋅6 ± 3⋅0 mg), zinc 84⋅0 % (3⋅9 ± 2⋅4 mg), selenium 30⋅2 % (11⋅3 ± 9⋅7 mcg), folate 73⋅8 % (93⋅6 ± 55⋅4 mcg), vitamin B12 94⋅4 % (0⋅2 ± 0⋅4 mcg), vitamin A 96⋅0 % (101⋅7 ± 94⋅1 mcg), and vitamin D 100⋅0 % (0⋅4 ± 0⋅6 mcg). Controlling for sex and socioeconomic status, the odds of biochemical deficiency with inadequate intake for iron [AOR = 1⋅37 (95 % CI 1⋅07-1⋅76)], zinc [AOR = 5⋅14 (95 % CI 2⋅24-11⋅78)], selenium [AOR = 3⋅63 (95 % CI 2⋅70-4⋅89)], folate [AOR = 1⋅59 (95 % CI 1⋅25-2⋅03)], and vitamin B12 [AOR = 1⋅62 (95 %CI 1⋅07-2⋅45)]. Since there is a significant association between the inadequate intake and biochemical deficiencies of iron, zinc, selenium, folate, and vitamin B12, regular surveillance for adequacy of micronutrient intake must be undertaken to identify children at risk of deficiency, for timely intervention.

Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma.

Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered). Here, we identify mosaic genetic alterations of 11p15.5 locus in the liver of hepatoblastoma patients without a clinical diagnosis of Beckwith-Wiedemann syndrome. We do not retrieve these alterations in children with other types of pediatric liver tumors. We show that mosaic 11p15.5 alterations in liver FFPE sections of hepatoblastoma patients display IGF2 overexpression and H19 downregulation together with an alteration of the liver zonation. Moreover, mosaic livers' microenvironment is enriched in extracellular matrix and angiogenesis. Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis.

Globicatella sanguinis corneal abscess with endophthalmitis.

Globicatella sanguinis is a rare microorganism known to affect the bloodstream, urinary tract, and central nervous system. We report a case of Globicatella sanguinis ocular infection in a 9-year-old boy, who presented with a corneal abscess with endophthalmitis, following trauma. Isolation of the infection using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and determination of its antibiotic sensitivity via Vitek 2 highlight the important role of microbiology laboratories for the diagnosis and management of infections caused by atypical microorganisms.

Comparison of contact lens-assisted and transepithelial corneal crosslinking with standard epithelium-off crosslinking for progressive keratoconus: 24-month clinical results.

PURPOSE: To compare the outcomes of contact lens-assisted corneal crosslinking (CACXL) and transepithelial CXL (TECXL) with standard epithelium-off (epi-off) CXL for progressive keratoconus. SETTING: Advanced Eye Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India. DESIGN: Retrospective, comparative study. METHODS: Patients with progressive keratoconus undergoing CXL with a minimum follow-up of 24 months were included. CACXL and TECXL were performed in patients with epithelium-on minimal pachymetry between 350 µm and 450 µm. The main outcome measures included change in maximum keratometry (Kmax), corrected distance visual acuity (CDVA), and efficacy in halting progression (increase in Kmax ≥1 diopter [D]). RESULTS: Standard epi-off CXL, CACXL, and TECXL were performed in 34, 14, and 10 eyes, respectively. Baseline Kmax and CDVA were comparable for all groups. Kmax reduced significantly by -2.83 ± 3.35 D, -3.18 ± 2.74 D, and -2.02 ± 1.66 D in the standard epi-off CXL (P < .01), CACXL (P = .001), and TECXL (P = .004) groups, respectively; the reduction was comparable for all groups (P = .63). CDVA improved by -0.14 ± 0.24, -0.04 ± 0.19, and -0.12 ± 0.17 logMAR in the standard epi-off CXL (P = .006), CACXL (P = .42), and TECXL (P = .05) groups, respectively; the reduction was comparable for all groups (P = .46). Progression was documented in 2 eyes (6%) in the standard epi-off CXL group and in 0 eyes of the CACXL and TECXL groups (P = .61). CONCLUSIONS: CACXL and TECXL were comparable with the standard epi-off CXL for progressive keratoconus.

Corneal and corneal epithelial thickness distribution characteristics in healthy North Indian eyes using spectral domain optical coherence tomography.

Purpose: To determine the pattern of corneal thickness and epithelial thickness distribution in healthy North Indian eyes by using spectral domain optical coherence tomography (SD-OCT). Methods: The observational study measured total corneal and epithelial thickness in the central 2 mm zone and eight sectors each in paracentral 2-5 mm (ring 1) and midperipheral 5-7 mm (ring 2) zones on SD-OCT. Results: The study included 67 eyes of 67 subjects with a male:female ratio of 32:35 and mean age of 25.04 ± 4.54 years. The mean central corneal and epithelial thicknesses were 505.97 ± 30.12 µm and 60.48 ± 8.37 µm, respectively. The epithelium of inferior and infero-nasal sectors in ring 1 and inferior sector in ring 2 was significantly thicker than the radially opposite sectors of the respective rings (P = 0.001; P = 0.01 and P = 0.02, respectively). Sector-wise analysis did not reveal any significant correlation between the total corneal thickness and epithelial thickness (all P > 0.05) except in the outer superior sector where there was a weak positive correlation (r = 0.28, P = 0.02). Central epithelial thickness in males (60.59 ± 9.28 µm) and females (60.37 ± 7.58 µm) was comparable (P = 0.91). Pachymetry was thinnest in the inferior, inferonasal, and inferotemporal sectors in 44.79% of eyes (n = 30), while thinnest epithelium was seen in the superior, superonasal, and superotemporal quadrants in 50.75% of eyes (n = 34). Conclusion: The epithelial thickness distribution in this sample of topographically normal healthy North Indian eyes was nonuniform and independent of the underlying corneal thickness. Epithelium was thinner in the superior cornea, whereas total corneal thickness was minimum in the inferior part.

Applications of Nanotechnology in Forest Management.

Relatively a new branch of technology, Nanotechnology has been found effective and applicable in various scientific disciplines. Its effectiveness has attracted many researchers to use it for solving various issues related to the natural resource management. Lots of studies have been carried out so far and published related to the applications of nanotechnology in climate science, forestry, agro-ecosystem, medical science and industrial sectors. Solving climate change issues in forestry sector, development of new nanomaterials for the management of forests from risks like drought, flood, salinity, fire, invasion, pathogen etc., water resource management in forest system, increasing energy efficiency of forests, improved forest produce, applications in forest based paper industries and other potential domains and its application has been reviewed in this paper along with some of frequently used nanomaterials, generally used or have potential to be used. Some industries currently using this technology are also enlisted. It was concluded that the nanotechnology has significant scope in the field of forestry as an enabling technology yet the future directions and requirements of applying nanotechnology in forestry sector are still in budding stage especially in India and may be applied at large scale by facilitating technical and legal institutions, large R&D grants and research collaborations.

Quantification of Iridotrabecular Contact in Primary Angle-Closure Disease.

PRECIS: Iridotrabecular contact (ITC), a measure of angle closure, can be quantified along with other angle parameters on anterior segment optical coherence tomography (ASOCT). Hence, angle changes and angle closure mechanisms can be detected predicting the efficacy of iridotomy. PURPOSE: To assess 360-degree ITC and ocular parameter changes, after laser peripheral iridotomy (LPI), in primary angle-closure disease (PACD) subgroups. METHODOLOGY: This was a prospective observational study including 90 subjects, 30 each of primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Anterior segment OCT parameters were measured before and 3 weeks after LPI ITC: central anterior chamber depth, lens vault, angle-opening distance, angle recess area, trabecular iris space area, trabecular iris angle at 500 and 750 µm from scleral spur. RESULTS: ITC was highest in PACG, 81.43%±22.39%, followed by PAC, 28.53%±21.30%, and PACS, 10.76%± 8.54% (P=0.011). There was a significant decrease in ITC in all 3 groups after iridotomy (P<0.001), with a residual ITC of 68.56%±26.44% in PACG, 18.23%±15.98% in PAC, and 5.13%±5.11% in PACS. A significant positive correlation was seen between the extent of ITC, baseline intraocular pressure, and visual field index. ITC was highest in eyes with exaggerated lens vault (77.3%±32.03%), as compared with eyes having a plateau iris configuration or relative pupillary block configuration (P<0.001). CONCLUSIONS: Iridotomy at any stage of PACD shows a significant decrease in ITC, with areas of residual ITC. Even in PACG, the iridotomy is effective in exposing parts of the trabecular meshwork that had contact earlier. Greater baseline ITC and postlaser ITC are a biomarker for higher intraocular pressure and greater visual field damage, which need lifelong review and appropriate management.

A Rare Case of Pediatric Lacrimal Sac: Squamous Cell Carcinoma.

A case of a 6-year-old boy presenting with epiphora, medial canthal swelling, and lymphadenopathy is reported. Biopsy revealed a poorly differentiated squamous cell carcinoma. The child underwent neoadjuvant chemotherapy and showed tumor progression after a remarkable initial response. This case highlights the atypical age of presentation of potentially fatal lacrimal sac malignancy. Further, it emphasizes the importance of knowing signs of lacrimal sac malignancy among ophthalmologists treating childhood epiphora where inflammatory etiologies are most common. A high index suspicion, thorough clinical examination, and knowledge of the signs of malignancy may avoid delay in diagnosis of this rare but life-threatening malignancy. [J Pediatr Ophthalmol Strabismus. 2019;56:e8-e11.].

Comparative Evaluation of Phacoemulsification Alone versus Phacoemulsification with Goniosynechialysis in Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: Comparative evaluation of phacoemulsification (phaco) alone versus phacoemulsification combined with goniosynechialysis (phacoGSL) in primary angle-closure glaucoma (PACG). DESIGN: Prospective, randomized, parallel group, active controlled trial. PARTICIPANTS: Patients with PACG. METHODS: A total of 120 consecutive patients with PACG were screened, of whom 80 met inclusion criteria, with PACG uncontrolled on maximal hypotensive therapy and were recruited. Patients were randomized into 2 groups and underwent phaco alone in group 1 or phacoGSL in group 2. The patients were examined at baseline and at 1 week and 1, 3, and 6 months. The anterior chamber angle parameters on swept-source anterior segment OCT (SS-ASOCT) were noted at 1 and 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was intraocular pressure (IOP) reduction. A reduction in IOP of ≥ 20% from baseline IOP with or without medications was considered a success. Secondary outcome measures included change in the anterior chamber angle temporal parameters, angle-opening distance, trabecular-iris space area and scleral spur angle, surgical safety, visual acuity, and reduction in the number of glaucoma medications postoperatively. RESULTS: The average age of patients was 58.77±8.14 years and 56.50±9.17 years in groups 1 and 2, respectively (P = 0.31). The mean baseline IOP was 29.48±6.76 mmHg and 30.72±3.88 mmHg in groups 1 and 2, respectively (P = 0.13). Success was obtained in 93.33% of patients in group 1 and 91.18% of patients in group 2 at 6 months (P = 0.39). Mean IOP was 13.17±1.66 mmHg and 13.21±1.97 mmHg at 6 months in groups 1 and 2, respectively (P = 0.001). The reduction in IOP was 55.32% and 56.99% at 6 months in groups 1 and 2 (P = 0.48). Significant widening of the angle parameters was noted at 6 months with an increase compared with baseline values in both groups. In multivariate analysis, the significant predictor of decrease in IOP was the higher baseline IOP. CONCLUSIONS: Both phaco and phacoGSL are associated with a significant reduction in IOP along with a noteworthy widening of the anterior chamber angle parameters. Both procedures succeeded in reducing the necessity of glaucoma medications postoperatively in PACG eyes. There is no additional benefit of phacoGSL over phaco in PACG.

Smartphone-aided Quantification of Iridocorneal Angle.

As the upgrading of smartphone technology revolutionizes the field of ophthalmic imaging, we put forward one more of its novel applications. This article presents the possibility of iridocorneal angle (ICA) estimation through smartphone-captured images. Such measured inferior ICA (at 6'o clock position) was comparable to the anterior segment optical coherence tomography measured trabecular iris angle at 500 µ at 270 degrees (P=0.06). They both had an excellent positive correlation (ρ=0.81, P<0.001). Therefore, smartphone image-aided angle estimation may be a simple, effective, and economical method for quantification of ICAs, paving a more evident way for identification of angle-closure disease.