Evaluation of Aav Capsids and Delivery Approaches for Hereditary Hemorrhagic Telangiectasia Gene Therapy.

Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous delivery of soluble FMS-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84 and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered intravenously (i.v.) or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1 f/f mice through i.v. injection followed by brain AVM induction. Transduced cells in different organs, vessel density and abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain ECs and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and skeletal muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. Delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1 f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.

Evaluation of AAV Capsids and Delivery Approaches for Hereditary Hemorrhagic Telangiectasia Gene Therapy.

Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous (i.v.) delivery of soluble Feline McDonough Sarcoma (FMS)-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84, and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered i.v. or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1f/f mice through i.v. followed by bAVM induction. Transduced cells in organs, vessel density, abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain endothelial cells (ECs) and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. The delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.

A Comprehensive Pilot Study to Elucidate the Distinct Gut Microbial Composition and Its Functional Significance in Cardio-Metabolic Disease.

Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden.

A Clinicopathologic Study of Urinary Bladder Lesions Amongst North Indian Population: An Experience From a Tertiary Care Centre.

BACKGROUND: Urinary bladder cancer (UBC) is amongst the most common urological malignancies. AIM: To study different types of urinary bladder lesions in the north Indian population and to correlate various clinical and pathological findings. MATERIALS AND METHODS: The present prospective study was conducted on 100 cases undergoing transurethral resection of bladder tumor (TURBT) and/or radical cystectomy over a period of 2.5 years followed by histopathological examination. Liquid-based cytology for malignant cells in urine was also performed. Immunohistochemistry was employed for tumor typing wherever needed. RESULTS: A total of 100 cases were studied. Male to female ratio was 15.7:1 and most of the patients were in the sixth decade (40%). Painless hematuria was the commonest clinical presentation (60%) and smoking was the commonest risk factor (80%). The most common lesion was infiltrating urothelial carcinoma seen in 72 cases followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) seen in eight cases. Grade and depth of invasion were assessed and correlated. Several variants of infiltrating urothelial carcinoma such as squamous differentiation, glandular differentiation, microcystic, clear cell, nested, and micropapillary were also identified. Clinical, cystoscopic and histopathological findings were correlated in all the cases. CONCLUSION: Infiltrating urothelial carcinoma high grade was the most common bladder lesion identified and muscle invasion was more common with higher-grade lesions. A decade-younger age group was found to be more affected in the present series. Urine cytology for malignant cells is useful for early diagnosis of cancer. Immunohistochemistry is an important ancillary adjunct.

Land use and land cover dynamics in the Upper Ganga Riverine Wetland: unraveling ecosystem services over two decades.

Anthropogenic activities have drastically transformed natural landscapes, profoundly impacting land use and land cover (LULC) and, consequently, the provision and functionality of ecosystem service values (ESVs). Evaluating the changes in LULC and their influence on ESVs is imperative to protect ecologically fragile ecosystems from degradation. This study focuses on a highly sensitive Upper Ganga riverine wetland in India, covering Hapur, Amroha, Bulandshahr, and Sambhal districts, which is well-known for its significant endemic flora and fauna. The study analyzes the subtle variability in ecosystem services offered by the various LULC biomes, including riverine wetland, built-up, cropland, forest, sandbar, and unused land. LULC classification is carried out using Landsat satellite imagery 5 and 8 for the years 2000, 2010, and 2020, using the random forest method. The spatiotemporal changing pattern of ESVs is assessed utilizing the value transfer method with two distinct value coefficients: global value coefficients (C14) for a worldwide perspective and modified local value coefficients X08 for a more specific local context. The results show a significant increase in built-up and unused land, with a corresponding decrease in wetlands and forests from 2000 to 2020. The combined ESVs for all the districts are worth US $5072 million (C14) and US $2139 million (X08) in the year 2000, which declined to US $4510 million (C14) and US $1770 million (X08) in the year 2020. The sensitivity analysis reveals that the coefficient of sensitivity (CS) is below one for all biomes, suggesting the robustness of the employed value coefficients in estimating ESVs. Moreover, the analysis identifies cropland, followed by forests and wetlands, as the LULC biomes most responsive to changes. This research provides crucial insights to stakeholders and policymakers for developing sustainable land management practices aimed at enhancing the ecological worth of the Upper Ganga Riverine Wetland.

CNS resident macrophages enhance dysfunctional angiogenesis and circulating monocytes infiltration in brain arteriovenous malformation.

Myeloid immune cells are abundant in both ruptured and unruptured brain arteriovenous malformations (bAVMs). The role of central nervous system (CNS) resident and circulating monocyte-derived macrophages in bAVM pathogenesis has not been fully understood. We hypothesize that CNS resident macrophages enhance bAVM development and hemorrhage. RNA sequencing using cultured endothelial cells (ECs) and mouse bAVM samples revealed that downregulation of two bAVM causative genes, activin-like kinase 1 (ALK1) or endoglin, increased inflammation and innate immune signaling. To understand the role of CNS resident macrophages in bAVM development and hemorrhage, we administrated a colony-stimulating factor 1 receptor inhibitor to bAVM mice with brain focal Alk1 deletion. Transient depletion of CNS resident macrophages at an early stage of bAVM development mitigated the phenotype severity of bAVM, including a prolonged inhibition of angiogenesis, dysplastic vasculature formation, and infiltration of CNS resident and circulating monocyte-derived macrophages during bAVM development. Transient depletion of CNS resident macrophages increased EC tight junction protein expression, reduced the number of dysplasia vessels and severe hemorrhage in established bAVMs. Thus, EC AVM causative gene mutation can activate CNS resident macrophages promoting bAVM progression. CNS resident macrophage could be a therapeutic target to mitigate the development and severity of bAVMs.

Liesegang Rings in a Patient With Pulmonary Tuberculosis: The First Report.

Liesegang rings are eosinophilic, concentric, lamellated structures that can assume a variety of shapes and sizes ranging from a few microns to hundreds of microns. To date, Liesegang rings have been reported in around 30 examples in the English literature, in the kidney, breast, female genital tract, and skin, and only a single report in the lung associated with allergic bronchopulmonary aspergillosis. Liesegang rings are usually incidental discoveries and have been associated with benign cystic lesions, inflammatory diseases, fibrosis, and tissue necrosis. Their typical appearance helps differentiate them from their mimics including parasites, foreign materials, corpora amylacae, and psammoma bodies. We report Liesegang rings in a 62-year-old male patient with pulmonary tuberculosis to create awareness about this rare entity among pathologists to avoid its misdiagnosis as a parasitic infection.

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse.

Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.

Parent's Perspective of Problems Faced during the COVID-19 Pandemic Lockdown on the Care of Children with Epilepsy: A Qualitative Study.

Background: COVID-19 has significantly impacted the care of children with chronic illness. There is a paucity of data on issues faced by parents of children with epilepsy (CWE) in an Indian setup. Objectives: The objective was to describe the parental perspective of the problems faced by them on the care of their CWE during the first wave of the COVID-19 pandemic. Materials and Methods: Parents of CWE who physically visited the clinic for their follow-up visit were asked to narrate their experiences about the problems they faced during the first lockdown due to COVID-19. The narratives were audio recorded, and transcripts were analyzed using thematic analysis to arrive at broad themes. Results: Four broad themes were identified: transport-related issues, medication-related issues, issues related to doctor consultation, and diagnostic delay. Limited transportation facilities, lack of appropriate social distancing norms in public transport and outpatient units, rigorous frisking by personnel during travel, fear of viral transmission during outpatient visits, nonavailability of antiseizure medications (ASMs) in local markets, lack of discounts by pharmacy, change of brands of ASM, and inability to undergo scheduled diagnostic investigations were some of the major issues raised by parents of CWE. Conclusion: Parents of CWE had trouble in transport to the hospital, inadequate access to ASMs, difficulties in doctor consultation, and delays in diagnostic investigations during the first COVID-19 pandemic lockdown.

Synchronous Occurrence of Adult Granulosa Cell Tumor with Fibroma in One Ovary and Brenner Tumor in Other Ovary: An Extremely Unusual Case.

Ovarian tumors are a common form of neoplasia in women and it accounts for about 30% of female genital cancers. A coexistence of ovarian tumors with the same histogenetic origin such as germ cell or epithelial or sex cord stromal, but different histologic subtype is relatively common, whereas a synchronous occurrence of tumors with different histogenetic origin is rare. We report a case of 58-year-old woman with the synchronous presentation of adult granulosa cell tumor with fibroma (ovarian tumors with the same origin (sex cord stromal) but different histologic type) in one ovary and Brenner tumor (epithelial origin) in other ovary. Our patient presented with postmenopausal bleeding and was diagnosed with this rare combination of ovarian tumors on histopathology supplemented with immunohistochemistry. On extensive literary search, there is only a single report of mixed ovarian tumor composed of Brenner tumor and adult-type granulosa cell tumor. Our case is different from the above-mentioned report as although, in our patient both tumors coexisted, but in contralateral ovaries.

Alzheimer's disease: Molecular aspects and treatment opportunities using herbal drugs.

Alzheimer's disease (AD), also called senile dementia, is the most common neurological disorder. Around 50 million people, mostly of advanced age, are suffering from dementia worldwide and this is expected to reach 100-130 million between 2040 and 2050. AD is characterized by impaired glutamatergic and cholinergic neurotransmission, which is associated with clinical and pathological symptoms. AD is characterized clinically by loss of cognition and memory impairment and pathologically by senile plaques formed by Amyloid ß deposits or neurofibrillary tangles (NFT) consisting of aggregated tau proteins. Amyloid ß deposits are responsible for glutamatergic dysfunction that develops NMDA dependent Ca2+ influx into postsynaptic neurons generating slow excitotoxicity process leading to oxidative stress and finally impaired cognition and neuronal loss. Amyloid decreases acetylcholine release, synthesis and neuronal transport. The decreased levels of neurotransmitter acetylcholine, neuronal loss, tau aggregation, amyloid ß plaques, increased oxidative stress, neuroinflammation, bio-metal dyshomeostasis, autophagy, cell cycle dysregulation, mitochondrial dysfunction, and endoplasmic reticulum dysfunction are the factors responsible for the pathogenesis of AD. Acetylcholinesterase, NMDA, Glutamate, BACE1, 5HT6, and RAGE (Receptors for Advanced Glycation End products) are receptors targeted in treatment of AD. The FDA approved acetylcholinesterase inhibitors Donepezil, Galantamine and Rivastigmine and N-methyl-D-aspartate antagonist Memantine provide symptomatic relief. Different therapies such as amyloid ß therapies, tau-based therapies, neurotransmitter-based therapies, autophagy-based therapies, multi-target therapeutic strategies, and gene therapy modify the natural course of the disease. Herbal and food intake is also important as preventive strategy and recently focus has also been placed on herbal drugs for treatment. This review focuses on the molecular aspects, pathogenesis and recent studies that signifies the potential of medicinal plants and their extracts or chemical constituents for the treatment of degenerative symptoms related to AD.

Correlation of Maternal Thyroid Stimulating Hormone Levels With Lipid Profile in Pregnant Women With Hypothyroidism.

Introduction Pregnancy leads to changes in hormonal levels and lipid profile. Thyroid hormones play a crucial role in embryonic growth and fetal development. Untreated thyroid disease during pregnancy can lead to a high risk of complications. Aim The aim of the study is to examine the correlation between thyroid stimulating hormone (TSH) and lipid profile in pregnant women with hypothyroidism. Materials and methods This cross-sectional case-control study was conducted at the Biochemistry Department, Alfalah School of Medical Science & Research Centre, Dhauj, Faridabad, Haryana, India. The study consisted of 500 patients (250 cases and 250 controls) who fulfilled the inclusion and exclusion criteria. Of the 250 cases recruited, 23 cases were in the 2nd trimester and 209 cases were in the 3rd trimester. Blood samples were collected from the participants to assess their lipid profile and TSH levels.  Results The study showed a statistically significant difference between the mean TSH levels of hypothyroid pregnant females in the 2nd trimester (3.85 ± 0.59) and the 3rd trimester (4.71 ± 0.54). There was a significant positive correlation observed between TSH and Total Cholesterol, Triglycerides, and LDL-C in both the 2nd and 3rd trimesters. In the second trimester, there was a significant positive correlation observed between TSH & TC (r = 0.6634, p<0.0005), TSH & TG (r= 0.7346, p=0.00006), TSH & LDL (r= 0.5322, p= 0.008). In the third trimester, there was a significant positive correlation observed between TSH & TC (r = 0.8929, p<0.00001), TSH & TG (r= 0.430, p<0.00001), TSH & LDL (r= 0.168, p= 0.015). However, no significant correlation was found between TSH levels and HDL-C in either trimester. The correlation coefficient and p-value for TSH & HDL were r = 0.2083, p=0.340 in the second trimester, and r = 0.0189, p=0.2384 in the third trimester. Conclusion A significant increase in TSH levels in hypothyroid pregnant women was observed in the 3rd trimester compared to the second trimester. Moreover, a significant positive correlation was found between TSH and lipid profile (total cholesterol, triglycerides, and LDL) in both trimesters, but not with HDL. These findings highlight the importance of monitoring thyroid hormone levels in the later stages of pregnancy to avoid potential maternal & fetal complications.

CNS resident macrophages enhance dysfunctional angiogenesis and circulating monocytes infiltration in brain arteriovenous malformation.

Myeloid immune cells present abundantly in both ruptured and unruptured brain arteriovenous malformations (bAVMs). The role of central nervous system (CNS) resident and circulating monocyte-derived macrophages in bAVM pathogenesis has not been fully understood. RNA sequencing using cultured cells and bAVM samples revealed that downregulation of activin-like kinase 1 (ALK1) or endoglin (two bAVM causative genes) increased pro-angiogenic, endothelial inflammation and innate immune signaling, which provided endogenous underpinnings of the active inflammation in bAVM. To further understand the role of CNS resident macrophages in bAVM development and hemorrhage, we administrated a colony-stimulating factor 1 receptor (CSF1R) inhibitor to bAVM mice with endothelial Alk1 deletion. Transient depletion of CNS resident macrophages at early stage of bAVM development remarkably mitigated the subsequent phenotype severity of bAVM. This therapeutic effect exhibited a prolonged inhibition of angiogenesis, dysplastic vasculature formation, and infiltration of CNS resident and circulating monocyte-derived macrophages during bAVM development. Transient depletion of CNS resident macrophages also reduced the dysplasia vessels and improved the integrity of endothelial tight junctions in established bAVMs. Administration of CSF1R inhibitor also prevented severe hemorrhage of bAVMs. Thus, endothelial AVM causative gene mutation can activate CNS resident macrophages promoting bAVM progression. CNS resident macrophages could be specific targets to mitigate the development and severity of bAVMs.

Expression of Epidermal Growth Factor Receptor (EGFR) and ß-catenin in Colorectal Carcinoma and its Correlation with Tumor Grade and Stage.

Colorectal cancer (CRC) is considered the result of the cumulative effect of multiple mutations within the cell that allow it to escape growth control and regulatory mechanisms. EGFR overexpression has been suggested as a factor of poor prognosis in various cancers. ß-catenin plays a role in the Wnt signaling pathway of colorectal cancers. An analytical cross-sectional study was conducted over a period of two years comprising 20 colectomy specimens. Clinicopathological details were documented, and immunohistochemistry (IHC) for EGFR and ß-catenin was performed. EGFR-Brown membranous staining was observed; ß-catenin-Brown membranous or nuclear staining was observed. IHC scoring was done, taking into account the intensity of staining and the percentage of positive tumor cells. The mean age of patients with colorectal carcinoma was 47.45 ± 14.8 (mean + SD) years. No statistically significant difference was noted in the EGFR immunoexpression and tumor grade (p value = 0.361) as well as the TNM stage (p value = 0.699). There was no statistically significant difference between ß-catenin immunoexpression and tumor grade (p value = 0.444) and TNM stage (p value = 0.911). A statistically significant difference was noted in the EGFR and ß-catenin immunoexpression (p = 0.0001). EGFR and ß-catenin expression was observed in 50% and 65% of cases, respectively. EGFR and ß-catenin expression was not associated with histological tumor grade and TNM stage of the tumor. In the present study, EGFR expression was significantly associated with ß-catenin immunoexpression.

Evaluating the Quantitative Foveal Avascular Zone and Retino-Choroidal Vessel Density Using Optical Coherence Tomography Angiography in a Healthy Indian Population.

OBJECTIVE: The foveal avascular zone (FAZ) is the round capillary-free zone within the macula and is supplied only by a single-layered parafoveal capillary arcade. This study aimed to evaluate the quantitative FAZ and retino-choroidal vessel density (VD) using optical coherence tomography angiography (OCTA) in a healthy Indian population. METHODS: This was a cross-sectional observational study that was conducted for evaluating the quantitative FAZ and retino-choroidal VD of 200 eyes of 100 healthy Indian subjects, including 62 males and 38 females (age range 17-50 years) having the best-corrected visual acuity (BCVA) of logMAR 0 (20/20; 6/6) and spherical equivalent refractive error of not more than 1 D. The subjects were examined using OCTA automated software on spectral-domain OCT (SD-OCT; Nidek RS 3000 Advance 2; Nidek, Inc., Fremont, CA) on a 3 x 3 mm OCTA macular scan centred on the fovea. The FAZ size, perimeter and circularity index, VD in superficial, deep, and outer retina (OR), outer retinal chorio-capillaries (ORCC), chorio-capillaries (CC) and choroid (C) were analysed in the circular and quadrant-segmented zones. A correlation was found between the FAZ size, perimeter and circularity, and VD in retino-choroidal layers, and between BCVA, age, central foveal thickness (CFT) and sub-foveal choroidal thickness (SFCT), and OCTA parameters. RESULTS: The FAZ and surrounding vascular arcades were intact in all eyes, showing either a vertical or horizontal oval-shaped symmetrical formation without gaps, holes or interruption of the capillary network. The mean value of CFT was 237.5±26.0 microns and SFCT was 269.6±53.0 microns. The mean FAZ area was 0.42±0.23 mm2, FAZ perimeter was 3.3±1.0 mm and FAZ circularity index was 0.46±0.1. The mean VD in superficial capillary plexus (SCP) was 23.87±10.66, in deep capillary plexus (DCP) was 16.03±9.90, in OR was 13.22± 12.27, in ORCC was 39.74±14.32, in CC was 37.02±16.43 and in choroid was 37.43±16.76. The increasing order of VD in different retino-choroidal layers was OR

Central Retinal Vein Occlusion Following the First Dose of COVID Vaccine.

The reports of vascular adverse events in the eye following COVID-19 vaccination are infrequent. We report the case of a healthy male who developed central retinal vein occlusion in his left eye three days following administration of the first dose of Covishield vaccine. As the underlying systemic and ocular risk factors were absent and laboratory investigations were normal, vein occlusion appeared to probably result from the vaccine. The patient developed retinal hemorrhages and non-perfusion ischemic areas all over the fundus. The macular edema was reduced with intravitreal triamcinolone acetonide, but the visual gain was not much, which appears to be due to the time lag in his initial presentation to the Ophthalmology Department. A close watch should be kept for ophthalmic adverse events to have an early intervention.

Predictors of Retinal Nerve Fiber Layer Parameters Following Scleral Buckling Surgery in Primary Rhegmatogenous Retinal Detachment.

OBJECTIVE: This study aimed to examine predictors of retinal nerve fiber layer (RNFL) parameters following scleral buckling (SB) surgery for primary rhegmatogenous retinal detachment (RRD) and to determine the influence of the magnitude of change in qualitative and quantitative parameters on RNFL. METHODS:  In an observational prospective study, 40 subjects who underwent successful retinal reattachment with SB surgery done within one month of RRD were evaluated for the parameters of best-corrected visual acuity (BCVA), refractive error, intraocular pressure (IOP), axial length (AL), anterior chamber depth (ACD), angle opening distance (AOD 500 and AOD 750), trabecular iris surface area (TISA 500 and TISA 750), visual fields, and ganglion cell count (GCC) and RNFL before and three months after SB. We additionally noted qualitative factors like extent, location, and type of buckle; phakic status; and grade of proliferative vitreoretinopathy in the affected eye. The change in value of quantitative parameters was found. The influence of baseline values and magnitude of change of quantitative and qualitative parameters on average RNFL thickness and magnitude of change of RNFL thickness after SB was found. RESULTS:  Post-SB, average RNFL thickness reduced from 108.58±20.38 microns to 103.73±17.98 microns (p =0.042). The baseline temporal upper (TU), temporal lower (TL), and nasal lower (NL) RNFL thickness (p=0.01, p=0.02, p=0.01, respectively) and total deviation (TD) values of visual fields (p=0.01) correlated positively while baseline GCC gross loss of volume (p=0.01) correlated negatively with post-operative RNFL thickness. The TU, TL, and NL RNFL thickness (p=0.04, p=0.01, p=0.01, respectively) and average GCC (p=0.04) correlated negatively with the magnitude of change in RNFL. The magnitude of change in baseline parameters after surgery was correlated with the magnitude of change in average RNFL thickness. It was noticed that change in AL (p<0.01), TISA 500 (p=0.02), TISA 750 (p<0.01), GCC focal loss of volume (p=0.02), and temporal RNFL thickness (p<0.01) correlated positively while the change in refractive error correlated negatively (p=0.04). Except for the grade of proliferative vitreoretinopathy (PVR) (p=0.04), none of the qualitative parameters, including extent, type, and location of the buckle; and phakic status, had a significant association with post-operative average RNFL thickness or magnitude of its change. CONCLUSIONS:  The predictors of average RNFL thickness following SB include AL; myopic shift; TISA; visual fields TD; average, TU, TL, and NL RNFL thickness; average GCC, gross and focal loss of volume; and grade of PVR. So an early surgery to prevent preoperative ganglion cell and RNFL loss and progression of PVR is recommended.