Use of 30 gauge needle to prevent hypotony during silicone oil removal.

Silicone oil (SO) is used as an intraocular tamponade after complex vitreoretinal surgeries because of its properties such as transparency, inertness, high surface tension, and interfacial tension with water. The only disadvantage of SO tamponade is the need for a second surgery for its removal. However, there is a risk of ocular hypotony soon after the removal of the infusion cannula, especially in retinal vascular conditions, such as diabetic retinopathy. We hereby present a silicone oil removal (SOR) technique using a 30 G needle that prevents intraocular hypotony during SOR.

Efficacy of a single injection of brolucizumab in neovascular age-related macular degeneration on visual acuity and micromorphometry.

Purpose: To assess short-term efficacy of a single injection of brolucizumab in neovascular AMD. Methods: This was a multicenter, retrospective chart review of 25 eyes of 25 patients who received a single injection of brolucizumab. Visual acuity (VA) and optical coherence tomography (OCT) features such as central subfield thickness (CSFT), subretinal fluid (SRF), intraretinal fluid, and pigment epithelial detachment (PED) were recorded at baseline, first month, and third month. Results: Of the 25 eyes, 14 eyes were treatment-naïve and 11 eyes had received previous injections. VA improved from 0.68 ± 0.59 log MAR at baseline to 0.31 ± 0.43 log MAR at the end of 3 months. SRF height in first and third month was significantly reduced from baseline (P < 0.001). Subretinal hyperreflective material height significantly reduced from baseline (P value 0.008 at first month and 0.01 at third month, respectively). CSFT was 464.16 ± 247.97 microns at baseline and showed a significant reduction in first month (P < 0.001) and third month (P < 0.001). There was a significant reduction of PED height from baseline at both follow-ups. None of the eyes showed a recurrence of fluid at the end of 3 months. Conclusion: Our study demonstrated sustained improvement in VA and OCT parameters after a single injection of brolucizumab at 3 months. A longer follow-up may demonstrate even farther effects of a single injection.

A case of eosinophilic granulomatous polyangiitis with concurrent central and peripheral nervous system involvement.

Eosinophilic granulomatous polyangiitis (EGPA) like other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has multisystemic involvement. It commonly manifests with prodromal pulmonary involvement as asthma, chronic sinusitis followed by systemic vasculitic complications associated with blood and tissue eosinophilia. Central nervous system manifestations at presentation are uncommon compared with peripheral nervous system involvement. Vasculitic neuropathy in EGPA commonly presents as mononeuritis multiplex but rarely as polyradiculopathy. Late onset EGPA often presents with systemic involvement, and early diagnosis is a key to prevent further complications. The neuropathy in late onset EGPA is often refractory to immunosuppression and corticosteroids treatment. We report a case of EGPA with late onset asthma presenting with acute infarct and demyelinating polyradiculoneuropathy that progressed with bulbar paralysis and profound dysautonomia. This illustrates simultaneous involvement of central and peripheral nervous system with EGPA. Autonomic dysfunction can occur in patients of EGPA with multisystem involvement, which may predict severe complications.

Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy-hippocampal sclerosis patients may limit the seizure outcomes.

BACKGROUND: Accumulation of reactive oxygen species (ROS) exacerbates neuronal loss during seizure-induced excitotoxicity. Keap1 (Kelch-like ECH-associated protein1)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis is one of the known active antioxidant response mechanisms. Our study focused on finding the factors influencing Keap1-Nrf2 axis regulation in temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients. METHODS: Based on post-surgical follow-up data, patient samples (n = 26) were categorized into class 1 (completely seizure-free) and class 2 (only focal-aware seizures/auras), as suggested by International League Against Epilepsy (ILAE). For molecular analyses, double immunofluorescence assay and Western blot analysis were employed. RESULTS: A significant decrease in expression of Nrf2 (p < 0.005), HO-1; p < 0.02) and NADPH Quinone oxidoreductase1 (NQO1; p < 0.02) was observed in ILAE class 2. Keap1 (p < 0.02) and histone methyltransferases (HMTs) like SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) (p < 0.009) and enhancer of zeste homolog 2 (EZH2; p < 0.02) and methylated histones viz., H3K4me1 (p < 0.001), H3K9me3 (p < 0.001), and H3K27me3 (p < 0.001) was upregulated in ILAE class 2. Nrf2-interacting proteins viz., p21 (p < 0.001) and heat shock protein 90 (HSP90; p < 0.03) increased in class 1 compared to class 2 patients. CONCLUSION: Upregulation of HMTs and methylated histones can limit phase II antioxidant enzyme expression. Also, HSP90 and p21 that interfere with Keap1-Nrf2 interaction could contribute to a marginal increase in HO-1 and NQO1 expression despite histone methylation and Keap1. Based on our findings, we conclude that TLE-HS patients prone to seizure recurrence were found to have dysfunctional antioxidant response, in part, owing to Keap1-Nrf2 axis. The significance of Keap1-Nrf2 signaling mechanism in generation of phase II antioxidant response. Keap1-Nrf2 controls antioxidant response through regulation of phase II antioxidant enzymes like HO-1 (heme oxygenase-1), NQO1 (NADPH-Quinone Oxidoreductase1), and glutathione S-transferase (GST). Release of Nrf2 from negative regulation by Keap1 causes its translocation into nucleus, forming a complex with cAMP response-element binding protein (CBP) and small Maf proteins (sMaf). This complex subsequently binds antioxidant response element (ARE) and elicits and antioxidant response involving expression of phase II antioxidant enzymes. Reactive oxygen species (ROS) modify Cysteine 151 residue, p62 (sequsetosome-1), and interacts with Nrf2- binding site in Keap 1. p21 and HSP90 prevent Nrf2 interaction with Keap1. At transcriptional level, histone methyltransferases like EZH2 (enhancer of zeste homologue2), and SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) and corresponding histone targets viz., H3K27me3, H3K9me3, and H3K4me1 influence Nrf2 and Keap1 expression respectively.

Dopamine and Glutamate Crosstalk Worsen the Seizure Outcome in TLE-HS Patients.

Temporal lobe epilepsy (TLE), accompanied by hippocampal sclerosis (HS), is the most common form of drug-resistant epilepsy (DRE). Nearly 20% of the patients showed seizure recurrence even after surgery, and the reasons are yet to be understood. Dysregulation of neurotransmitters is evident during seizures, which can induce excitotoxicity. The present study focused on understanding the molecular changes associated with Dopamine (DA) and glutamate signaling and their possible impact on the persistence of excitotoxicity and seizure recurrence in patients with drug-resistant TLE-HS who underwent surgery. According to the International League against Epilepsy (ILAE) suggested classification for seizure outcomes, the patients (n = 26) were classified as class 1 (no seizures) and class 2 (persistent seizures) using the latest post-surgery follow-up data to understand the prevalent molecular changes in seizure-free and seizure-recurrence patient groups. Our study uses thioflavin T assay, western blot analysis, immunofluorescence assays, and fluorescence resonance energy transfer (FRET) assays. We have observed a substantial increase in the DA and glutamate receptors that promote excitotoxicity. Patients who had seizure recurrence showed a significant increase in (pNR2B, p < 0.009; and pGluR1, p < 0.01), protein phosphatase1γ (PP1γ; p < 0.009), protein kinase A (PKAc; p < 0.001) and dopamine-cAMP regulated phospho protein32 (pDARPP32T34; p < 0.009) which are critical for long-term potentiation (LTP), excitotoxicity compared to seizure-free patients and controls. A significant increase in D1R downstream kinases like PKA (p < 0.001), pCAMKII (p < 0.009), and Fyn (p < 0.001) was observed in patient samples compared to controls. Anti-epileptic DA receptor D2R was found to be decreased in ILAE class 2 (p < 0.02) compared to class 1. Since upregulation of DA and glutamate signaling supports LTP and excitotoxicity, we believe it could impact seizure recurrence. Further studies about the impact of DA and glutamate signaling on the distribution of PP1γ at postsynaptic density and synaptic strength could help us understand the seizure microenvironment in patients. Dopamine, Glutamate signal crosstalk. Diagram representing the PP1γ regulation by NMDAR negative feedback inhibition signaling (green circle-left) and D1R signal (red circle-middle) domination over PP1γ though increased PKA, pDARPP32T34, and supports pGluR1, pNR2B in seizure recurrent patients. D1R-D2R hetero dimer activation (red circle-right) increases cellular Ca2+ and pCAMKIIα activation. All these events lead to calcium overload in HS patients and excitotoxicity, particularly in patients experiencing recurrent seizures.

Long-Term Seizure Freedom, Resolution of Epilepsy and Perceived Life Changes in Drug Resistant Temporal Lobe Epilepsy With Hippocampal Sclerosis: Comparison of Surgical Versus Medical Management.

BACKGROUND: Outcome of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) has rarely been evaluated exclusively. OBJECTIVE: To compare long-term seizure freedom, resolution of epilepsy, and perceived life changes in patients with drug-resistant TLE-HS who underwent surgery vs those who opted for best medical management. METHODS: In this retrospective longitudinal study, 346 patients with TLE-HS who underwent surgery were compared with 325 who received best medical management. Predictors for long-term remission, resolution of epilepsy, and seizure recurrence were analyzed. RESULTS: The duration of follow-up ranged from 3-18 (mean 12.61) years. The average age of study population was 28.54 ± 12.27 years with 321 (47.8%) women. Age at onset of epilepsy (11.84 ± 8.48 vs 16.29 ± 11.88; P ≤ .001) was lower, and duration of epilepsy (15.65 ± 9.33 vs 12.97 ± 11.44; P < .001) was higher in the surgery group. Seizure freedom at 3 (81.8 vs 19.0%; P < .001), 5 (73% vs 16.1%; P < .001), and 10 years (78.3% vs 18.5; P < .001) and resolution of epilepsy (30.5% vs 0.6%; P < .001) was higher in the surgery group. The overall perceived life changes score was higher in the surgery group (80.96 ± 25.47 vs 66.24 ± 28.13; P < .001). At long-term follow-up (≥10 years), the presence of an aura was the strongest predictor for resolution of epilepsy (ß: 2.29 [95% CI; 1.06-4.93]; P = .035), whereas acute postoperative seizures (APOS) (ß: 6.06 [95% CI 1.57-23.42]; P < .001) and an abnormal postoperative EEG (ß: 0.222 [95% CI 0.100-0.491]; P < .001) were predictors of persistent seizures. Seizure freedom both at 3 and 5 years predicted seizure freedom at 10 years. CONCLUSION: Surgery for drug-resistant TLE-HS was associated with higher rate of long-term seizure-freedom, resolution of epilepsy, and reduction of anti-seizure medications with improvement in perceived life changes compared with best medical management. The presence of an aura was predictor for resolution of epilepsy while APOS and an abnormal postoperative EEG were predictors of persistent seizures.

Endoplasmic reticulum stress and unfolded protein accumulation correlate to seizure recurrence in focal cortical dysplasia patients.

Epileptic seizures occur due to an imbalance between excitatory and inhibitory neurosignals. The excitotoxic insults promote the accumulation of reactive oxygen species (ROS), unfolded proteins (UFP) aggregation, and sometimes even cell death. The epileptic brain samples in our study showed significant changes in the quantity of UFP accumulation. This part explored the efficiency of ER stress and autophagy responses at neutralizing the UFP using resected epileptic brain tissue samples. Meanwhile, we regularly observed these patients' post-surgical clinical data to find the recurrence of seizures. According to International League against Epilepsy (ILAE) suggestions, we classified the patients (n = 26) as class 1 (completely seizure-free), class 2 (less frequent seizures or auras), and class 3 (auras with < 3 seizures per year). The classification helped us understand the reason for variations in the UFP accumulation in patient samples. We have observed the protein levels of ER chaperone, glucose-regulated protein 78 kDa (GRP78/BiP), inositol-requiring enzyme 1α (IRE1α), X box-binding protein 1 s (XBP1s), eukaryotic translation initiation factor 2α (peIF2α), C/EBP homologous protein (CHOP), NADPH oxidase (NOX2), and autophagy proteins like BECLIN1, ATG 7, 12, 5, 16, p62, and LC3. Our results suggested that ER stress response limitation may contribute to seizure recurrence in epilepsy patients, particularly in classes 2 and 3. In addition, we have observed significant upregulation of ER stress-dependent apoptosis initiation factor CHOP in these patients. These results indicate that understanding the ER stress response pattern infers the possibility of post-surgical outcomes in focal cortical dysplasia (FCD) patients.

Impact of COVID-19 pandemic, national lockdown, and unlocking on an apex tertiary care ophthalmic institute.

PURPOSE: To evaluate the impact of 2019 COVID-19 pandemic, national lockdown, and unlocking on ophthalmic care provided by the government-funded apex health institute of India. METHODS: Retrospective review of electronic medical records of all patients presenting to the ophthalmology department from March 23, 2020, to July 15, 2020, was compared with that from March 23, 2019, to July 15, 2019. The data between March 23, 2020, to May 31, 2020 (lockdown) and June 06, 2020, to July 15, 2020 (unlock) was compared separately. Parameters evaluated were age, gender, presenting complaints, final diagnosis, treatment advised, and surgical interventions. RESULTS: During the lockdown, routine outpatient flow reduced by 97.14% (P < 0.001), the median age of presentation decreased to 29 years (55 years last year) and males increased by 4.7% (from 61.51% to 66.21%) in 2020. Emergency services decreased by 35.25%, percentage of children decreased by 4.28% (from 34.28% to 30%) and males increased by 13.53% (from 59.97% to 73.5%). Mechanical trauma, microbial keratitis, and conjunctivitis were the most common reasons for presentation. The former lessened by 41.75% while the latter two amplified by 1.25 times and 2 times, respectively. While sanitizer-associated chemical injury increased in proportion, endophthalmitis, and postoperative complications declined. The number of donor corneas collected and emergency therapeutic keratoplasties performed decreased by 99.61% and 92.39%, respectively (P < 0.001). During the unlocking phase, routine patient consultations were 71 ± 19/day, significantly lower than 978 ± 109/day of last year (P < 0.001). No voluntary eye donation was reported during this period. CONCLUSION: COVID-19 pandemic and national lockdown severely hampered the delivery of ophthalmic care by the apex-ophthalmic institute. Unlike anticipated, lifting of pandemic-associated lockdown served only minimally in improving patient inflow in its initial phases.

Inter-ictal EEG patterns in malformations of cortical development and epilepsy.

OBJECTIVES: Malformations of cortical Development (MCDs) are associated with refractory epilepsy. We evaluated scalp inter-ictal EEG patterns in various types of MCD, and its association with clinical features and seizure control. PATIENTS AND METHODS: Retrospective analysis of demographic, clinical, inter-ictal EEG and seizure outcome data of 665 patients with epilepsy and MCD with at least two years follow up was performed. RESULTS: Average age of study population was 15.95 ± 10.79 years with 291(43.8 %) women. Multiregional spikes were more common in children (22.7 % vs 8.5; p < 0.001), if age of onset of epilepsy was <2 years (21.8 % vs 11.4 %; p = 0.001) and polymicrogyria (12.1 % vs 37.3 %; p < 0.001). Generalized epileptiform discharges were more frequent in patients with developmental delay (24.7 % vs 12.6 %; p < 0.001); and were associated with lissencephaly(14.0 % vs 59.3 %; p < 0.001) and heterotopias(14.5 % vs 34.9 %;p = 0.002). Regional spikes were more common if age of onset of epilepsy is >2 years (26.2 % vs 38.4 %; p = 0.003), and also in FCD (17.1 % vs 42.6 %; p < 0.001). At latest follow-up, 151(22.7 %) patients were seizure free; 401(60.7 %) had refractory epilepsy and the rest had remissions with relapse. No association was found between inter-ictal EEG patterns and seizure control. CONCLUSION: In patients with MCD, generalized epileptiform discharges were associated with developmental delay, lissencephaly and heterotopias. Regional spikes were frequent in FCD while multiregional spikes in children and polymicrogyria. Inter-ictal EEG patterns did not influence seizure outcome.

Rare atypical presentation of phacolytic glaucoma as non-resolving microbial keratitis with endophthalmitis.

Phacolytic glaucoma (PLG) is a rare complication of hypermature senile cataract. Delayed presentation of PLG may make its diagnosis and management difficult and worsen its prognosis. A woman aged 75 years complaining of sleep disturbing pain and inaccurate projection of rays oculus dextrus (OD) was referred to our centre for management of non-resolving microbial keratitis with endophthalmitis. Ultrasound biomicroscopy revealed 360° peripheral anterior synechiae, swollen crystalline lens and hyperechoic granules filling anterior chamber. A diagnosis of PLG and lens-induced uveitis was made and cataract was extracted after control of intraocular pressure (IOP). The patient was left aphakic. There was complete resolution of pain after surgery and at 3 months follow-up the IOP was controlled without any antiglaucoma medications. Rarely, secondary corneal opacification from long-standing pathological changes in PLG may mimic non-resolving microbial keratitis with endophthalmitis and requires a high index of suspicion for appropriate diagnosis and management.

Effects of Punica granatum on milk-induced leucocytosis and eosinophilia in mice / Efecto de Punica granatum en ratas con leucocitosis y eosinofilia inducida por leche

Punica granatum Linn. (Punicaceae) commonly known as Pomegranate is a dark greenish large deciduous shrub or small tree, about 5-10 m height. Flower buds are traditionally used in the treatment of asthma and allergy. The aim of this study was to validate the traditional antiallergic property using milk-induced leucocytosis and milk-induced eosinophilia in rats. Flower buds of the plant were extracted successively using various solvents to obtain the respective extracts. These extracts were administered to mice at the dose of 50 and 100 mg/kg, orally. Only the ethanol extract showed significant reduction in leukocyte and eosinophil count, these results are a validation of the use of the extract of polar compounds of P. granatum flower buds as an antiallergic agent.

Punica granatum Linn. (Punicaceae) comúnmente conocida como granada es un pequeño árbol o arbusto grande de hoja caduca, de unos 50-10 m de altura y de color verde oscuro. Los botones florales se utilizan tradicionalmente en el tratamiento del asma y la alergia. El objetivo de este estudio fue validar la propiedad tradicional antialérgica utilizando ratas con leucocitosis y eosinofilia inducida por leche. Los botones florales de la planta se extrajeron sucesivamente con varios solventes para obtener los extractos respectivos. Estos extractos se administraron a los ratones a dosis de 50 y 100 mg / kg, por vía oral. Sólo el extracto obtenido con etanol mostró una reducción significativa en el recuento de leucocitos y eosinófilos, estos resultados son una validación del uso del extracto de compuestos polares de los botones florales de P. granatum como un agente antialérgico.