Evaluation of Visual Cortex Activity using Functional Near-Infrared Spectroscopy (fNIRS) in Primary Open Angle and Primary Angle Closure Glaucoma: A pilot study.

PRECIS: Functional Near Infrared Spectroscopy was used to assess visual cortical activity in patients with primary open angle and primary angle closure glaucoma. There was decreased activity in the visual cortex of glaucoma patients correlating with the severity of glaucoma. PURPOSE: To evaluate visual cortex activity using fNIRS (Functional Near Infrared Spectroscopy) in primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) compared to healthy controls. METHODS: A total of 30 POAG, 31 PACG, and 30 healthy aged-matched controls from a single centre were recruited in this cross-sectional observational pilot study with purposive sampling. The POAG and PACG groups were age-matched but were not matched for disease severity at recruitment. All participants underwent fNIRS testing using a multi-channel continuous-wave near infra-red system NIRSport 8×7 device (NIRx Medizintechnik GmbH, Berlin, Germany). The visual cortex activity was evaluated in terms of maximum amplitude of change in oxyhemoglobin (OxyHb) concentration over 10 seconds and a comparison was done between three groups. Both POAG and PACG groups were combined (termed as glaucoma group) to assess relationship of visual cortical activity with disease severity {by visual field defect (mean deviation) and retinal nerve fiber layer (RNFL) thickness}. RESULTS: All participants showed the characteristic response of increased OxyHb and decreased DeoxyHb during stimulus presentation. The maximum amplitude of change in OxyHb concentration over 10 seconds was significantly lower in both POAG and PACG groups compared to control in the right and left middle occipital gyri (P<0.05). There was no significant difference between PACG and POAG. Importantly, there was a negative correlation of the visual cortex activity with the visual field defects (mean deviation) (P<0.05) and a positive correlation with RNFL thickness in the glaucoma group (P<0.05). CONCLUSION: In glaucoma patients, reduction in visual cortical activity was observed which may be indicative of neuronal degeneration occurring in the occipital cortex. Disease severity in glaucoma appears to be closely correlated with visual cortex activity. fNIRS can serve as a useful neuroimaging modality for assessing the hemodynamic and neurodegenerative changes in glaucoma.

Measuring Visual Fields in Children With Glaucoma Using a Portable Tablet.

Purpose: To compare perimetric outcomes of an iPad perimetry app (Melbourne Rapid Fields [MRF]) with those of the Humphrey Field Analyser (HFA) testing children with glaucoma. Methods: Sixteen children diagnosed and treated for glaucoma were recruited to evaluate their perimetric performance over two visits. At each visit, they undertook visual field assessment using the MRF application as well as the HFA. The HFA test was part of their usual clinical work up and a clinical assistant judged which test format (24-2 SITA standard or SITA fast) might be suited to the testing of that child. The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests, by way of regression, intraclass correlation coefficient and Bland-Altman analysis. Secondary measures were comparisons of pattern deviation indices, test times as well as an indication of participant test preference. Summary data show means ± standard deviation. Results: The age for our cohort was 7 to 15 years of age (mean, 10.0 ± 2.4 years of age). The MRF MD was in close concordance to HFA MD with an intraclass correlation coefficient of 0.91 (95% confidence interval, 0.82-0.95). Bland-Altman analysis found little bias (-0.6 dB) and a 95% coefficient of repeatability of 2.1 dB in eyes having a normal HFA MD. In eyes with glaucomatous visual field defects the 95% coefficient of repeatability at retest was much larger for both the MRF (10.5 dB) as well as for the HFA (10.0 dB). Average MRF test times (5.6 ± 1.2 minutes) were similar to SITA Fast (5.4 ± 1.9 minutes) with both being significantly faster than SITA standard (8.6 ± 1.4 minutes; P < 0.001). All children chose testing with the MRF as their preference. Conclusions: MRF correlated strongly with HFA and was preferred by the children over the HFA. MRF is suitable for perimetric evaluation of children with glaucoma. Translational Relevance: This study finds that an iPad based visual field test can be used with children having glaucoma to yield outcomes similar to SITA-fast. Children indicate a preference for such testing.

A Cross-Sectional Study Examining the Relationship Between Malnutrition and Gross Motor Function in Cerebral Palsy.

Introduction Cerebral palsy (CP) characterizes a range of permanent, nonprogressive symptoms of postural and motor dysfunction caused by an insult to the developing central nervous system in a fetus or an infant. CP manifests early in life, often within the first two to three years of age. CP is associated with poor growth, that is the deviation from the normal growth parameters. The prevalence of CP ranges from 2.0 to 3.5 per 1000 live births in high-income countries which is comparable to the estimates from low-income countries. Antenatal and perinatal insults are among the most commonly reported causes of CP; however, a large number of cases do not have an identifiable etiology of CP. The current study aims to examine the relationship between malnutrition and gross motor function in children with CP. Materials and Methods This study was conducted at the Department of Pediatrics and Neonatology, Nehru Hospital, Baba Raghav Das (BRD) Medical College, Gorakhpur (UP) over a period of one year (August 2020 to July 2021) after obtaining ethical clearance from the College Research Council. Children of age 1-15 years with CP attending the pediatric outpatient and inpatient departments were enrolled as the study participants after obtaining informed consent from a legal guardian. Assessment of motor function was done using the gross motor function classification system (GMFCS). Associations of malnutrition across levels of gross motor function were tested using Chi-square or Fisher's exact test whichever was applicable. Statistical significance was set at p < 0.05 as significant. Data was analyzed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Result We analyzed 110 children with a diagnosis of CP (median age 6.5 years, interquartile range (IQR) 4.4-9.0 years). The majority (65/110; 59%) of the patients were male, and 68 (61.8%) delivered at term gestation. The most common presenting symptom among children with CP was seizures (79/110; 72.3%), the second most common being delayed milestones among 73 (66.8%), followed by difficulty in breathing among 63 (57.5%). The association between the anthropometric index of participants and GMFCS was found to be highly significant. Conclusion Most CP patients were facing gross motor disturbances. Spastic type of CP was most frequent, and more than half of the patients experienced feeding difficulty. A statistically significant association was found between gross motor functioning and the prevalence of malnutrition and stunting.

Identification of potential targetable genes in papillary, follicular, and anaplastic thyroid carcinoma using bioinformatics analysis.

PURPOSE: To perform an extensive exploratory analysis to build a deeper insight into clinically relevant molecular biomarkers in Papillary, Follicular, and Anaplastic thyroid carcinomas (PTC, FTC, ATC). METHODS: Thirteen Thyroid Cancer (THCA) datasets incorporating PTC, FTC, and ATC were derived from the Gene Expression Omnibus. Genes differentially expressed (DEGs) between THCA and normal were identified and subjected to GO and KEGG analyses. Multiple topological properties were harnessed and protein-protein interaction (PPI) networks were constructed to identify the hub genes followed by survival analysis and validation. RESULTS: There were 70, 87, and 377 DEGs, and 23, 27, and 53 hub genes for PTC, FTC, and ATC samples, respectively. Survival analysis detected 39 overall and 49 relapse-free survival-relevant hub genes. Six hub genes, BCL2, FN1, ITPR1, LYVE1, NTRK2, TBC1D4, were found common to more than one THCA type. The most significant hub genes found in the study were: BCL2, CD44, DCN, FN1, IRS1, ITPR1, MFAP4, MKI67, NTRK2, PCLO, TGFA. The most enriched and significant GO terms were Melanocyte differentiation for PTC, Extracellular region for FTC, and Extracellular exosome for ATC. Prostate cancer for PTC was the most significantly enriched KEGG pathway. The results were validated using TCGA data. CONCLUSIONS: The findings unravel potential biomarkers and therapeutic targets of thyroid carcinomas.

Reduced Aqueous Humor Outflow Pathway Arborization in Childhood Glaucoma Eyes.

Purpose: To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Methods: Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Results: Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Conclusions: Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Translational Relevance: Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.

Machine learning-assisted prediction of trabeculectomy outcomes among patients of juvenile glaucoma by using 5-year follow-up data.

OBJECTIVE: To develop machine learning (ML) models, using pre and intraoperative surgical parameters, for predicting trabeculectomy outcomes in the eyes of patients with juvenile-onset primary open-angle glaucoma (JOAG) undergoing primary surgery. SUBJECTS: The study included 207 JOAG patients from a single center who met the following criteria: diagnosed between 10 and 40 years of age, with an IOP of >22 mmHg in the eyes on two or more occasions, open angle on gonioscopy in both eyes, with glaucomatous optic neuropathy, and requiring a trabeculectomy for IOP control. Only the patients with a minimum 5-year follow-up after surgery were included in the study. METHODS: A successful surgical outcome was defined as IOP ≤18 mmHg (criterion A) or 50% reduction in IOP from baseline (criterion B) 5 years after trabeculectomy. Feature selection techniques were used to select the most important contributory parameters, and tenfold cross-validation was used to evaluate model performance. The ML models were evaluated, compared, and prioritized based on their accuracy, sensitivity, specificity, Matthew correlation coefficient (MCC) index, and mean area under the receiver operating characteristic curve (AUROC). The prioritized models were further optimized by tuning the hyperparameters, and feature contributions were evaluated. In addition, an unbiased relationship analysis among the parameters was performed for clinical utility. RESULTS: Age at diagnosis, preoperative baseline IOP, duration of preoperative medical treatment, Tenon's thickness, scleral fistulation technique, and intraoperative mitomycin C (MMC) use, were identified as the main contributing parameters for developing efficient models. The three models developed for a consensus-based outcome to predict trabeculectomy success showed an accuracy of >86%, sensitivity of >90%, and specificity of >74%, using tenfold cross-validation. The use of intraoperative MMC and a punch for scleral fistulation compared to the traditional excision with scissors were significantly associated with long-term success of trabeculectomy. CONCLUSION: Optimizing surgical parameters by using these ML models might reduce surgical failures associated with trabeculectomy and provide more realistic expectations regarding surgical outcomes in young patients.

Comparative posterior corneal profile of keratoconus hydrops versus Haab's striae in congenital glaucoma.

Keratoconus eyes develop corneal decompensation more often compared to eyes with primary congenital glaucoma (PCG) following Descemet's membrane (DM) tear. This study was conducted to compare the posterior corneal morphology in areas with DM breaks with regards to DM and pre-Descemet's layer (PDL) between the two. In this cross-sectional comparative study, anterior segment optical coherence tomography (AS-OCT) scans of the posterior cornea of advanced keratoconus eyes with hydrops ( n = 12), PCG eyes with Haab's striae ( n = 15), and healthy control eyes ( n = 14) were compared for DM-PDL morphology. These were further corroborated by the histopathology of corneal buttons from keratoconus ( n = 14) and PCG ( n = 13) cases obtained following penetrating keratoplasty and compared with controls (enucleated retinoblastoma globes, n = 6) on light microscopy and collagen IV immunostaining. AS-OCT showed a thicker median DM/PDL complex in PCG (80 µm) versus keratoconus eyes (36 µm, P = 0.01; Kruskal-Wallis test). The median height and length of detached DM-PDL were significantly more in keratoconus versus PCG (145 µm, 1766.1 ± 1320.6 µm vs. 26.5 µm, 453.3 ± 303.2 µm, respectively, P = 0.012; Kruskal-Wallis test). Type-1 DM/PDL detachment (seen as a characteristic taut chord) in keratoconus (90%) was the most common morphological pattern versus intracameral twin protuberance (92%) following DM breaks in PCG. Histopathology confirmed thicker DM in PCG (median: 63.4 µm) versus keratoconus eyes (median: 33.2 µm) or controls (27.1 µm) ( P = 0.001; Kruskal-Wallis test). Greater height/length of DM/PDL detachment compounded by poor healing response (lower DM/PDL thickness) probably causes more frequent corneal decompensation in keratoconus eyes when compared to PCG eyes following DM tears.

Effect of "365 Breathing Technique" on Intraocular Pressure and Autonomic Functions in Patients With Glaucoma: A Randomized Controlled Trial.

PRCIS: Patients with primary open angle glaucoma were advised to follow the "365 breathing technique" for 6 weeks in addition to their pharmacological glaucoma treatment. It helped to reduce intraocular pressure (IOP), stress biomarker-cortisol, and improve autonomic dysfunction. OBJECTIVE: To study the effect of the "365 breathing technique" on IOP, autonomic functions, and stress biomarkers in patients with primary open angle glaucoma. METHODS: In this randomized, controlled, interventional trial, after randomization, 40 patients in the intervention group followed "365 breathing" (three times a day, breathing rate: 6 cycles/min for 5 min) in addition to their pharmacological glaucoma treatment and 40 patients in the control group continued only with their pharmacological glaucoma treatment. IOP, serum cortisol, heart rate variability (HRV), and heart rate response to deep breathing test (DBT) were recorded at preintervention and 6 weeks postintervention. RESULTS: The mean IOP, serum cortisol, parameters of the HRV test, and DBT were comparable between the two groups at baseline. At the 6-week follow-up, in the intervention group, mean IOP was significantly lower (16.09 ± 2.24 vs 18.38 ± 1.58 mm Hg, P = 0.03) and serum cortisol were significantly lower (13.20 ± 3.11 vs 14.95 ± 2.60 mcg/dL, P = 0.038) compared with the control group. In the HRV test, time domain analysis showed a significant difference in the root mean square of the successive difference between RR interval values between both groups at 6 weeks ( P = 0.015) pointing towards higher postintervention parasympathetic activation in the intervention group. In frequency domain analysis (HRV test), the ratio of the low-frequency component to the high-frequency component was significantly lower in the intervention group at 6 weeks (1.65 vs 1.79, P = 0.019) indicating a shift in sympathovagal balance towards greater vagal modulation.There was a significant increase in delta heart rate ( P = 0.019) and expiratory:inspiratory ratio ( P = 0.011) in the intervention group at 6 weeks when compared with baseline values, indicating improved parasympathetic reactivity to DBT. CONCLUSION: "365 breathing" technique can reduce IOP and serum cortisol, and improve autonomic dysfunction in patients with glaucoma.

Stress and Allostatic Load in Patients With Primary Open Angle Glaucoma.

PRCIS: This study evaluated the allostatic load (AL) in primary open angle glaucoma (POAG) patients and reported that the AL score was significantly higher in glaucoma patients compared with age-matched controls. PURPOSE: To evaluate the AL in patients with POAG. METHODS: This case-control study comprised 50 POAG (glaucoma patients) and 50 age-matched controls without glaucoma (controls). AL was estimated based on 13 variables: systolic blood pressure (BP), diastolic BP, homocysteine, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, body mass index, serum cortisol, glycosylated hemoglobin, albumin, creatinine clearance, and C-reactive protein. High-risk thresholds were determined based on biological cutoffs of each biomarker. One point was assigned for each biomarker reading above cutoff and were summated to obtain AL score; score ≥4 was considered high. RESULTS: Mean age of glaucoma patients was 60.82±6.26 and 60.14±6.72 years in controls ( P =0.602). All components of AL score (except C-reactive protein) had higher values in glaucoma patients. There was a statistically significant difference in homocysteine ( P =0.001), total cholesterol ( P =0.037), high-density lipoprotein ( P =0.005), and glycosylated hemoglobin ( P =0.003). Mean AL score was 4.68±2.09 in glaucoma patients and 3.32±1.34 in controls ( P <0.001). There was significant association of high AL score with older age ( P =0.006), low socioeconomic status ( P =0.020), and glaucoma severity ( P =0.001). Negative correlation was seen between AL and retinal nerve fiber layer thickness (Right Eye: r =-0.37, P <0.001; Left Eye: r =-0.298, P <0.001) and visual field mean deviation (Right Eye: r =-0.469, P <0.001; Left Eye: r =-0.520, P <0.001). CONCLUSIONS: Glaucoma patients exhibited allostatic overload indicating physiological dysregulation to chronic stress although additional research is required to establish causality. A holistic approach with lifestyle modifications to reduce chronic stress should be an integral part of managing glaucoma patients as it would serve both to possibly reduce or prevent disease progression and improve overall health outcomes.

Indocyanine green-assisted goniotomy in eyes with hazy cornea.

Corneal haze, due to edema or opacity, is a major contraindication for performing ab interno angle surgeries such as goniotomy in children with primary congenital glaucoma (PCG), despite otherwise favorable surgical outcomes expected in these patients. In this case series involving patients of PCG with moderate corneal haze, the authors describe a technique for performing goniotomy in cases with compromised visibility by using indocyanine green (ICG) to aid in the visualization of angle structures. The authors used 0.2% ICG intracamerally, which stained the anterior and posterior trabecular meshwork (TM) with different intensities, before proceeding with goniotomy. The junction between the two zones was discernible due to the contrast imparted by ICG staining, despite poor visibility, allowing the surgeon to incise the TM at the correct site. The possibility of performing goniotomy in such patients with the help of ICG can revolutionize our surgical approach to patients with PCG and corneal edema.

In vivo identification of angle dysgenesis and its relation to genetic markers associated with glaucoma using artificial intelligence.

PURPOSE: To predict the presence of angle dysgenesis on anterior-segment optical coherence tomography (ADoA) by using deep learning (DL) and to correlate ADoA with mutations in known glaucoma genes. PARTICIPANTS: In total, 800 high-definition anterior-segment optical coherence tomography (AS-OCT) images were included, of which 340 images were used to build the machine learning (ML) model. Images used to build the ML model included 170 scans of primary congenital glaucoma (16 patients), juvenile-onset open-angle glaucoma (62 patients), and adult-onset primary open-angle glaucoma eyes (37 patients); the rest were controls (n = 85). The genetic validation dataset consisted of another 393 images of patients with known mutations that were compared with 320 images of healthy controls. METHODS: ADoA was defined as the absence of Schlemm's canal, the presence of hyperreflectivity over the region of the trabecular meshwork, or a hyperreflective membrane. DL was used to classify a given AS-OCT image as either having angle dysgenesis or not. ADoA was then specifically looked for on AS-OCT images of patients with mutations in the known genes for glaucoma. RESULTS: The final prediction, which was a consensus-based outcome from the three optimized DL models, had an accuracy of >95%, a specificity of >97%, and a sensitivity of >96% in detecting ADoA in the internal test dataset. Among the patients with known gene mutations, ( MYOC, CYP1B1, FOXC1, and LTBP2 ) ADoA was observed among all the patients in the majority of the images, compared to only 5% of the healthy controls. CONCLUSION: ADoA can be objectively identified using models built with DL.

Early discoveries on enzyme deficiencies in lysosomal storage diseases: The Indian contribution.

The discovery of enzyme deficiencies in lysosomal storage disorders began with two discoveries made in 1963. One of these was made by a Belgian scientist, Henri-Gery Hers, who discovered that in Pompe's disease there was a deficiency in α-glucosidase. The other was made by an international collaboration involving an American neurologist, James Austin, and an Indian biochemist, Bimal Bachhawat, where the enzyme arylsulfatase A was found deficient in metachromatic leukodystrophy. This article attempts to trace the events that led to this fruitful collaboration and how these two young investigators eventually discovered the defective enzyme in metachromatic leukodystrophy.

Estimation of 10-year cardiovascular risk among adult population in western Nepal using nonlaboratory-based WHO/ISH chart, 2023: A cross-sectional study.

Background and Aims: Noncommunicable diseases have emerged as a major cause of morbidity and mortality worldwide among which the majority of the deaths are caused by cardiovascular diseases. Estimating the risk of cardiovascular diseases helps eliminate the risk factors and prevent developing cardiovascular diseases in the future. The World Health Organization in association with the International Society of Hypertension has developed risk charts for the estimation of 10-year risk for cardiovascular diseases. This study aimed to estimate 10-year cardiovascular risk in the Nepalese population using nonlaboratory-based charts. Methods: A hospital-based cross-sectional study was conducted among 314 adults aged 40-74 years visiting the outpatient departments of Shishuwa Hospital in western Nepal. Systematic random sampling was used to select the participants. Questionnaire-guided short interviews, physical examination, and anthropometric measurements were done. The χ 2 test was used to test the significance and a p < 0.05 was considered statistically significant. Results: As per the risk estimation charts, high cardiovascular risk (20%-30%) was seen in 6.1% of total participants and moderate cardiovascular risk (10%-20%) was found in 29% of participants. The moderate-high risk was significantly higher among male participants compared to females (p < 0.01). Of all the participants, 22.0% were current smokers, 17.2% were alcohol users, 61.1% were hypertensive, and 35.7% were diabetics. Smoking tobacco, alcohol use, and hypertension were significantly more prevalent among the male participants. (p < 0.01) Adults in the 50-59 years age group had a significantly high prevalence of hypertension (p < 0.01), diabetes (p = 0.02), and alcohol abuse (p = 0.01). Conclusion: This study shows high cardiovascular risk among adult population in western Nepal. The 10-year cardiovascular risk score and risk factors were significantly higher among males than females. There seems to be a prompt necessity of health promotion interventions to reduce cardiovascular risk factors and prevent the burden of cardiovascular diseases in Nepal.