Clinicopathological profile, management and clinical outcomes in recurrent cases of ocular surface squamous neoplasia at a tertiary care centre.

PURPOSE: This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12 months and secondary outcome measure was complication associated with each treatment modality. RESULTS: The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12 months of follow-up in all 18 cases. CONCLUSION: The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.

Surgical outcomes of tarsofrontalis sling surgery using silicon rod versus supramaximal levator resection in unilateral congenital ptosis with poor levator function.

PURPOSE: To compare the surgical outcomes of tarsofrontalis sling surgery using silicon rod versus supramaximal levator resection in patients of unilateral congenital ptosis with poor levator function (≤ 4 mm). MATERIALS AND METHODS: This randomized control study was conducted over a period of 18 months. 44 patients were enrolled in the study group. The study population was randomly divided into two groups (22 in each group). In Group A, congenital ptosis was treated with tarsofrontalis sling surgery using silicon rod and supramaximal levator resection was done in the group B. Follow-up examination was done at postoperative day 1, one week, 1 month, 6 months and 12 months. Surgical outcome measures were change in marginal reflex distance-1 (MRD 1), vertical palpebral fissure height (VPFH) and inter-eyelid difference of margin reflex distance 1 and complications in two groups. RESULTS: The mean age of patients in group A was 7.25 ± 6.10 years ranging from 1-18 years and mean age of patients in group B was 5.64 ± 2.44 years ranging from 3 to 11 years. Good surgical outcome was obtained in 73-77% of both groups. MRD1and VPFH increased significantly after surgery from baseline in both the groups (p value < 0.001). Inter-eyelid MRD 1 difference also improved significantly in both groups following ptosis surgery. CONCLUSION: Both supramaximal levator resection and tarsofrontalis sling surgery are equally effective in cases of unilateral ptosis patients with poor levator function and should be part of the surgical armamentarium for treating congenital ptosis.

Corneal transplantation: A walk to vision.

Corneal diseases are a major cause of blindness in the world. Corneal transplantation has been a cornerstone in the management of several of these advanced pathologies. This article discusses the evolution of corneal transplantation over a century, its indications, complications and briefly the various surgical techniques. Such tremendous technical improvisations from total corneal transplantation to lamellar keratoplasties have generated significant interest in the ophthalmic world and garnered momentum to the fight against blindness. Armed Forces Medical Services are also in vogue more than ever in this forward surge.

Efficacy and safety of injection Botulinum toxin in canalicular obstruction due to trauma.

Background: The treatment of epiphora has undergone tremendous change in the past, and minimally invasive techniques are being preferred over traditional surgical options. One of them is the use of Inj Botulinum toxin, but there are very few studies that have explored its role in treating post-traumatic epiphora. This study was undertaken to find out the safety and efficacy of injection Botulinum toxin in treating epiphora due to canalicular obstruction following trauma. Methods: A longitudinal interventional study was done, and a total of 50 patients were recruited. All patients were subjected to Inj Botulinum toxin in the lacrimal gland (10 units). The study was done for a period of 6 months, and patients were followed up for a period of another 6 months. Changes in Munk score, Schirmer test, and tear meniscus height were considered the main outcome measures. Results: In our study, there were 38 males and 12 females. The age of the patients varied from 24 yrs to 67 yrs. Inj Botulinum toxin was found to be effective in 80% (n = 40/50) of cases as they reported a reduction in watering from eyes after administration of this injection. The complication associated with this treatment was minimal in our study as four patients reported diplopia, whereas two patients developed Ptosis that resolved spontaneously within two months. Conclusion: Inj Botulinum toxin was found to be effective in epiphora caused by canalicular obstruction due to trauma. This treatment should be considered as an alternative treatment modality as it often leads to satisfactory reduction in epiphora in patients with less complications compared to surgical intervention.

Recurrent spontaneous subluxation of the eye globe managed with orbital decompression: A case report with literature review.

Spontaneous subluxation of the eyeball is a rare phenomenon as there are only few cases reported in the literature. It is a sight-threatening condition and very traumatising for the patient. The globe has to be reposited back within the socket immediately to save vision and to prevent exposure keratitis and optic neuropathy. In all published reports about subluxation of the eyeball, the underlying aetiology which was responsible for this condition was found. Herein, we report a case of recurrent spontaneous subluxation of the eyeball in which the cause could not be ascertained in a middle-aged male patient even after thorough clinical examination and investigation. The case was managed successfully with three-wall orbital decompression and tarsorrhaphy. The patient did not experience any episode of subluxation of the globe following surgery as orbital decompression increased the available space for the orbital contents, thereby averting its occurrence.

Mechanisms of Coronary Ischemia in Women.

PURPOSE OF REVIEW: Obstructive coronary artery disease is a major cause of ischemia in both men and women; however, women are more likely to present with ischemia in the setting of no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA), conditions that are associated with adverse cardiovascular prognosis despite absence of coronary stenosis. In this review, we focus on mechanisms of coronary ischemia that should be considered in the differential diagnosis when routine anatomic clinical investigation leads to the finding of non-obstructive coronary artery disease on coronary angiography in the setting of acute myocardial infarction. RECENT FINDINGS: There are multiple mechanisms that contribute to MINOCA, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction (CMD), coronary embolism and/or thrombosis, and spontaneous coronary artery dissection. Non-coronary causes such as myocarditis or supply-demand mismatch should also be considered on the differential when there is an unexplained troponin elevation. Use of advanced imaging and diagnostic techniques to determine the underlying etiology of MINOCA is feasible and helpful, as this has the potential to guide management and secondary prevention. Failure to identify the underlying cause(s) may result in inappropriate treatment and inaccurate counseling to patients. MINOCA predominates in young women and is associated with a guarded prognosis. The diagnosis of MINOCA should prompt further investigation to determine the underlying cause of troponin elevation. Patients with INOCA and MINOCA are heterogeneous, and response to treatments can be variable. Large randomized controlled trials to determine longer-term optimal medical therapy for management of these conditions are under investigation.

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

BACKGROUND: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. METHODS: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4  M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBFACH ). RESULTS: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBFACH ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBFACH change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina. CONCLUSION: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.

Evolving Landscape of Clinical Trials in Heart Failure: Patient Populations, Endpoint Selection, and Regions of Enrollment.

PURPOSE OF REVIEW: Clinical trial design and execution are evolving as increasingly important considerations with respect to the success of heart failure trials. The current review highlights temporal trends in characteristics of heart failure clinical trials. RECENT FINDINGS: Recent trials in heart failure have required longer recruitment phases, displayed inefficient enrollment rates, increased use of composite and nonfatal endpoints, undergone rapid globalization, and gradually increased focus on heart failure with preserved ejection fraction. Understanding patterns and trends in clinical trial design and execution may inform future planning and conduct of trials of heart failure therapeutics.

Role of non-receptor tyrosine kinases in epilepsy: significance and potential as therapeutic targets.

INTRODUCTION: Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include >20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed. AREAS COVERED: Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy. To date, several nRTK members have been linked to processes relevant to the development of epilepsy. Therefore, in this review, we provide insight into the molecular mechanisms by which the various nRTK subfamilies can contribute to the pathogenesis of epilepsy. We further highlight the prospective use of specific nRTK inhibitors in the treatment of epilepsy deriving evidence from existing literature providing a rationale for their use as therapeutic targets. EXPERT OPINION: Specific small-molecule inhibitors of NRTKs can be employed for the targeted therapy as already seen in other diseases by examining the precise molecular pathways regulated by them contributing to the development of epilepsy. However, the evidence supporting NRTKs as therapeutic targets are limiting in nature thus, necessitating more research to fully comprehend their function in the development and propagation of seizures.

Clinicodemographic profile, management, and treatment outcomes in advanced retinoblastoma at a tertiary care center in North India.

PURPOSE: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. METHODS: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. RESULTS: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. CONCLUSION: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

Safety and efficacy of indigenously developed Ruthenium-106 eye plaque for brachytherapy of a spectrum of ocular tumors: A case series.

ABSTRACT: Various treatment modalities are available for treatment of ocular tumors, which include chemotherapy, laser, and radiotherapy (external beam radiation therapy or brachytherapy). Brachytherapy using plaque applicator is preferred over external beam radiation therapy when the tumor is well localized, as this therapy delivers radiation dose to the tumor with lower doses to normal tissues in the vicinity. However, plaque therapy is expensive and beyond the reach of many poor patients in India. The Bhabha Atomic Research Center (BARC) recently introduced an indigenous Ruthenium-106 plaque to make brachytherapy treatment available and affordable to all needy patients in India. In the present case series, we report our experience using the indigenous Ru-106 plaque for the treatment of a spectrum of ocular tumors.

Epigenetics of neurological diseases.

Higher-order DNA structure and gene expression are governed by epigenetic processes like DNA methylation and histone modifications. Abnormal epigenetic mechanisms are known to contribute to the emergence of numerous diseases, including cancer. Historically, the chromatin abnormalities were only considered to be limited to discrete DNA sequences and were thought to be associated with rare genetic syndrome however, recent discoveries have pointed to genome-wide level changes in the epigenetic machinery which has contributed to a better knowledge of the mechanisms underlying developmental and degenerative neuronal problems associated with diseases such as Parkinson's disease, Huntington's disease, Epilepsy, Multiple sclerosis, etc. In the given chapter we describe the epigenetic alterations seen in various neurological disorders and further discuss the influence of these epigenetic changes on developing novel therapies.

Epigenetics in epilepsy.

Epilepsy affects over 50 million individuals globally, making it the most prevalent chronic and serious neurological condition. A precise therapeutic strategy is complicated by poor understanding of the pathological changes in epilepsy thus, 30% of TLE patients are resistant to drug therapy. In the brain, epigenetic processes translate information from transient cellular impulses and adjustments in neuronal activity into long-lasting impacts on gene expression. Research suggests that epigenetic processes can be manipulated in the future to treat or prevent epilepsy as epigenetics has been shown to have a profound influence on how genes are expressed in epilepsy. As well as being potential biomarkers for epilepsy diagnosis, epigenetic changes can also be used as prognostic indicators of treatment response. In this chapter, we review the most recent findings in several molecular pathways linked with the pathogenesis of TLE that are controlled by epigenetic mechanisms highlighting their potential utility as biomarkers for upcoming treatment strategies.

Stent underexpansion is associated with high wall shear stress: a biomechanical analysis of the shear stent study.

Coronary stent underexpansion is associated with restenosis and stent thrombosis. In clinical studies of atherosclerosis, high wall shear stress (WSS) has been associated with activation of prothrombotic pathways, upregulation of matrix metalloproteinases, and future myocardial infarction. We hypothesized that stent underexpansion is predictive of high WSS. WSS distribution was investigated in patients enrolled in the prospective randomized controlled study of angulated coronary arteries randomized to undergo percutaneous coronary intervention with R-ZES or X-EES. WSS was calculated from 3D reconstructions of arteries from intravascular ultrasound (IVUS) and angiography using computational fluid dynamics. A logistic regression model investigated the relationship between WSS and underexpansion and the relationship between underexpansion and stent platform. Mean age was 63±11, 78% were male, 35% had diabetes, mean pre-stent angulation was 36.7°±14.7°. Underexpansion was assessed in 83 patients (6,181 IVUS frames). Frames with stent underexpansion were significantly more likely to exhibit high WSS (> 2.5 Pa) compared to those without underexpansion with an OR of 2.197 (95% CI = [1.233-3.913], p = 0.008). There was no significant association between underexpansion and low WSS (< 1.0 Pa) and no significant differences in underexpansion between R-ZES and X-EES. In the Shear Stent randomized controlled study, underexpanded IVUS frames were more than twice as likely to be associated with high WSS than frames without underexpansion.

Chemoselective amide formation using O-(4-nitrophenyl)hydroxylamines and pyruvic acid derivatives.

A series of O-(4-nitrophenyl)hydroxylamines were synthesized from their respective oximes using a pulsed addition of excess NaBH(3)CN at pH 3 in 65-75% yield. Steric hindrance near the oxime functional group played a key role in both the ease by which the oxime could be reduced and the subsequent reactivity of the respective hydroxylamine. Reaction of the respective hydroxylamines with pyruvic acid derivatives generated the desired amides in good yields. A comparison of phenethylamine systems bearing different leaving groups revealed significant differences in the rates of these systems and suggested that the leaving group ability of the N-OR substituent plays an important role in determining their reactivity with pyruvic acid. Competition experiments (in 68% DMSO/phosphate buffered saline) using 1 equiv of N-phenethyl-O-(4-nitrophenyl)hydroxylamine and 2 equiv of pyruvic acid in the presence of other nucleophiles such as glycine, cysteine, phenol, hexanoic acid, and lysine demonstrated that significant chemoselectivity is present in this reaction. The results suggest that this chemoselective reaction can occur in the presence of excess α-amino acids, phenols, acids, thiols, and amines.

Stigma towards dependent drinking and its role on caregiving burden: A qualitative study from Goa, India.

INTRODUCTION: Stigma towards alcohol use disorders is prevalent in India and can lead to social exclusion and hamper treatment access and outcomes. Family members of individuals with dependent drinking are often their primary caregivers and play a key role in decisions around help-seeking, treatment and recovery. The nature and role of stigma in caregiving, and the consequent burden on family caregivers of those with dependent drinking, has not been qualitatively studied in India. METHODS: We conducted in-depth interviews with: (i) men with probable alcohol dependence (n = 11); (ii) family caregivers (n = 12); and (iii) doctors with experience of treating alcohol dependence (n = 13) in community settings in Goa. Data were analysed using inductive thematic analysis. RESULTS: Two primary themes were identified from the data: (i) stigma in the form of ignorance, prejudice and discrimination; and (ii) the impact of this stigma on caregiving decisions and the mental health of caregivers. DISCUSSION AND CONCLUSIONS: We found that stigma functioned as a barrier to a proper course of treatment and care, as well as a detrimental factor for caregiver's mental health and caregiving decision-making. Stigma towards dependent drinking in the forms of ignorance, prejudice and discrimination is prevalent within homes, workplaces and health systems and might exacerbate the caregiving burden among female family caregivers. Policies, educational programs and campaigns aimed at preventing stigma in these forms would likely enable access to more inclusive and appropriate health services, benefit the health of family caregivers and improve the treatment outcomes of drinkers.

Post-corneal transplant Candida keratitis - Incidence and outcome.

PURPOSE: To report the risk factors, clinical characteristics, and outcomes of Candida keratitis following corneal transplantation in India. METHODS: On retrospective review of medical records of 789 patients, 31 eyes developed a graft infection following corneal transplantation or keratoprosthesis and we could identify the Candida infection in only five. These cases were operated at two tertiary care centers in India. These five records were reviewed for demographics, risk factors (local and systemic) for graft infection, characteristics of infective lesion, corneal scraping results, treatment plan, and the final outcome following management. RESULTS: The median age of the subjects with the Candida graft infection was 62.4 ± 10.33 years (range, 62-71 years). All patients were males. The predominant risk factors included repeat corneal transplantation (5/5), prolonged usage of topical steroids (5/5), and epithelial defects (4/5). The clinical characteristics included infiltrates of variable configuration like powdery deposits, white plaque, fluffy white infiltrate, and crystalline keratopathy. The smear showed budding yeasts in all five cases whereas culture was positive in four out of five cases. The final outcome with antifungals (systemic [4/5] and topical [5/5]) is variable. Two eyes underwent evisceration, two eyes had scar formation in the failed grafts, and one patient succumbed to the systemic disease 1-month post-corneal infection. CONCLUSION: Candida keratitis, in India, seems to be an emerging pathology following corneal transplantation and has a varied presentation. Though the outcomes following management seem to be grim, however, such infection can easily be avoided by a timely reduction of the risk factors.

Efficacy and safety of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration: a randomized trial in Indian patients.

BACKGROUND: The current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks. METHODS: A prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed. RESULTS: Brolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (-0.13 ± 0.21 logMAR vs. -0.10 ± 0.15 logMAR) and reduction in CMT (-112.59 ± 81.23 µm vs. -86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group. CONCLUSION: The results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals. Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName = .

Innovative technique of mini-simple limbal epithelial transplantation in pediatric patients.

In this article, we introduce a modified technique of minor ipsilateral simple limbal epithelial transplantation (mini-SLET) in pediatric patients of limbal stem cell deficiency (LSCD). Two children with unilateral partial LSCD underwent the innovative technique of mini-SLET, where harvested limbal tissues were placed over the raw cornea and were covered with amniotic membrane. Both patients were followed till 9 months. Both cases showed favorable outcome and uneventful recovery. Results were comparable with the classical technique. This innovative modification of mini-SLET is safe, feasible, and an effective alternative with favorable visual outcome especially in pediatric population. It can be a breakthrough for LSCD management in developing countries with limited resources.