Anterior Chamber Biometric Parameters Associated With Intraocular Pressure Reduction After Phacoemulsification in Non-Glaucomatous Eyes With Open Angles.

BACKGROUND: Decreased intra-ocular pressure after cataract surgery has been reported in eyes with and without glaucoma with variable magnitude. It is influenced by the anatomical structure of the anterior chamber. Preoperative evaluation of anterior chamber parameters can help to predict the change in intra-ocular pressure postoperatively. OBJECTIVE: The objective of the study is to evaluate intraocular pressure (IOP) change after uneventful phacoemulsification in non-glaucomatous eyes with open angles and its correlation with preoperative anterior chamber parameters measured by anterior segment optical coherence tomography (AS-OCT). METHODS: In this hospital-based prospective observational study, we included consecutive patients without glaucoma and open angles on gonioscopy who had undergone uncomplicated phacoemulsification with intraocular lens implantation (IOL). IOP and anterior chamber biometric parameters were measured preoperatively and compared with parameters obtained three months post-operatively by AS-OCT. The change in IOP and its relation to the parameters, including anterior chamber angle (ACA), anterior chamber depth (ACD), angle opening distance 500 µm anterior to the scleral spur (AOD500), anterior chamber width (ACW), lens vault (LV), and trabecular iris space area (TISA500) were evaluated. The main outcome measure was a change in IOP after phacoemulsification in normal eyes. RESULTS: Sixty-four eyes of 64 patients were enrolled. The mean patient age was 58.5 ± 9.4 years. The average IOP reduction was 2.43±1.64 mm of Hg from a preoperative mean of 16.77±2.54 mmHg three months after phacoemulsification surgery. The mean AOD500 increased significantly (0.440 ± 0.07 to 0.522 ±0.092) from preoperatively to three months postoperatively (p < 0.001). Preoperative lens vault and preoperative IOP had a strong positive correlation with the change in IOP at three months (r-value = 0.606; p-value <0.001) and (r-value = 0.73; p-value <0.001). There was a significant negative correlation between pre-operative TISA and AOD with change in IOP at three months (r-value = -0.545; p-value <0.001) and (r-value = -0.69; p-value <0.01). CONCLUSION:  Phacoemulsification surgery results in IOP reduction in non-glaucomatous eyes. Pre-operative IOP, lens vault, AOD, and TISA were significant predictors for IOP reduction.

Age-related cataract - Prevalence, epidemiological pattern and emerging risk factors in a cross-sectional study from Central India.

Purpose: To study the epidemiological pattern, prevalence, types, and correlates of age-related cataracts in a tertiary care center in central India. Methods: This hospital-based single-center cross-sectional study was conducted on 2,621 patients diagnosed with cataracts for 3 years. Data pertaining to demography, socio-economic profile, cataract grading, cataract types, and associated risk factors were evaluated. Statistical analysis using unadjusted odds ratio (OR) and multivariate logistic regression was performed, with P-value <0.05 considered significant with the power of the study being 95%. Results: The commonest age group affected was 60-79 years, closely followed by the 40-59 years age group. The prevalence of nuclear sclerosis (NS), cortical (CC), and posterior subcapsular cataract (PSC) was found to be 65.2% (3,418), 24.6% (1,289), and 43.4% (2,276), respectively. Among mixed cataracts, (NS + PSC) had the highest prevalence of 39.8%. Smokers were found to have 1.17 times higher odds of developing NS than non-smokers. Diabetics had 1.12 times higher odds of developing NS cataracts and 1.04 times higher odds of developing CC. Patients with hypertension showed 1.27 times higher odds of developing NS and 1.32 times higher odds of developing CC. Conclusion: The prevalence of cataracts in the pre-senile age group (<60 years) was found to have increased significantly (35.7%). A higher prevalence of PSC (43.4%) was found in studied subjects, as compared to the data of previous studies. Smoking, diabetes, and hypertension were found to have a positive association with a higher prevalence of cataracts.

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Single-molecule analysis reveals widespread structural variation in multiple myeloma.

Multiple myeloma (MM), a malignancy of plasma cells, is characterized by widespread genomic heterogeneity and, consequently, differences in disease progression and drug response. Although recent large-scale sequencing studies have greatly improved our understanding of MM genomes, our knowledge about genomic structural variation in MM is attenuated due to the limitations of commonly used sequencing approaches. In this study, we present the application of optical mapping, a single-molecule, whole-genome analysis system, to discover new structural variants in a primary MM genome. Through our analysis, we have identified and characterized widespread structural variation in this tumor genome. Additionally, we describe our efforts toward comprehensive characterization of genome structure and variation by integrating our findings from optical mapping with those from DNA sequencing-based genomic analysis. Finally, by studying this MM genome at two time points during tumor progression, we have demonstrated an increase in mutational burden with tumor progression at all length scales of variation.

Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis.

BACKGROUND: Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective. RESULTS: Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci. CONCLUSIONS: The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics.

An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription.

Although microRNAs (miRNAs) are important regulators of gene expression, the transcriptional regulation of miRNAs themselves is not well understood. We employed an integrative computational pipeline to dissect the transcription factors (TFs) responsible for altered miRNA expression in ovarian carcinoma. Using experimental data and computational predictions to define miRNA promoters across the human genome, we identified TFs with binding sites significantly overrepresented among miRNA genes overexpressed in ovarian carcinoma. This pipeline nominated TFs of the p53/p63/p73 family as candidate drivers of miRNA overexpression. Analysis of data from an independent set of 253 ovarian carcinomas in The Cancer Genome Atlas showed that p73 and p63 expression is significantly correlated with expression of miRNAs whose promoters contain p53/p63/p73 family binding sites. In experimental validation of specific miRNAs predicted by the analysis to be regulated by p73 and p63, we found that p53/p63/p73 family binding sites modulate promoter activity of miRNAs of the miR-200 family, which are known regulators of cancer stem cells and epithelial-mesenchymal transitions. Furthermore, in chromatin immunoprecipitation studies both p73 and p63 directly associated with the miR-200b/a/429 promoter. This study delineates an integrative approach that can be applied to discover transcriptional regulatory mechanisms in other biological settings where analogous genomic data are available.

High-resolution human genome structure by single-molecule analysis.

Variation in genome structure is an important source of human genetic polymorphism: It affects a large proportion of the genome and has a variety of phenotypic consequences relevant to health and disease. In spite of this, human genome structure variation is incompletely characterized due to a lack of approaches for discovering a broad range of structural variants in a global, comprehensive fashion. We addressed this gap with Optical Mapping, a high-throughput, high-resolution single-molecule system for studying genome structure. We used Optical Mapping to create genome-wide restriction maps of a complete hydatidiform mole and three lymphoblast-derived cell lines, and we validated the approach by demonstrating a strong concordance with existing methods. We also describe thousands of new variants with sizes ranging from kb to Mb.

Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart.

To investigate the transcriptional response to oxidative stress in the heart and how it changes with age, we examined the cardiac gene expression profiles of young (5-mo-old), middle-aged (15-mo-old), and old (25-mo-old) C57BL/6 mice treated with a single intraperitoneal injection of paraquat (50 mg/kg). Mice were killed at 0, 1, 3, 5, and 7 h after paraquat treatment, and the gene expression profile was obtained with high-density oligonucleotide microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the old mice displayed a significant change in mRNA levels (ANOVA, P < 0.01). Among these, a total of 55 transcripts were determined to be paraquat responsive for all age groups. Genes commonly induced in all age groups include those associated with stress, inflammatory, immune, and growth factor responses. Interestingly, only young mice displayed a significant increase in expression of all three isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of immediate early response genes (IEGs) found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart.