Ocular Surface Squamous Neoplasia in Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare genetic disorder associated with multiple oculocutaneous and neurological manifestations. It occurs due to deficiency of the enzymes responsible for repairing ultraviolet radiation-induced DNA damage. Persistence of un-repaired DNA results in somatic mutations, leading to neoplasia of the skin and ocular surface. As this condition is rare, only isolated case reports of XP with ocular surface squamous neoplasia (OSSN) are found in literature

Visual benefits and complications following neodymium-doped yttrium aluminum garnet (Nd: YAG) capsulotomy

Background: The incidence of posterior capsule opacification (PCO) noted at the end of 5 years following cataract extraction is 33%. With the advent of phacoemulsification various materials and designs of intraocular lenses, the incidence of PCO has been reduced. Following pediatric cataract surgery, the incidence of PCO was found to be 100%. Nd: YAG capsulotomy is considered a safe, effective, and non-invasive technique to treat PCO. Aims and Objectives: The aim of the study was to evaluate the visual acuity among the patients with PCO and to assess the complications following Nd: YAG capsulotomy. Materials and Methods: A total of 100 eyes of 100 patients with study period being 2 years from October 2015 to July 2017. The study was prospective study, and sampling was purposive sampling. After recruiting, the participants were divided into 2 case groups - pseudophakia and aphakia. A complete ophthalmological evaluation was done which included best-corrected visual acuity, torchlight and slit-lamp examination, and measurement of IOP which was followed by a fundus examination. Results: The minimum and maximum age of the patient observed in our study was 34 and 88. Most of the study population was in the age group of 51–60 years. Majority of patients presented with PCO with an interval of 25–36 months following cataract surgery and were noted in about 52% of study population. Majority of the patients had visual acuity 6/36-6/18 and observed in 36% of study population. Comparison between pre-YAG and post-YAG day 1 visual acuity was done using significance test and P=0.000 which was highly significant, visual acuity at 4th week was compared to that of 6th week, and it was significant. Conclusion: The loss of vision due to PCO is a distressing complication for a patient who has spent time and money getting their surgery done and finds that their vision is dropping again. YAG laser capsulotomy is a simple, outpatient solution that will bring the smile back on the patient’s face instantly. Capsulotomy improves visual acuity immediately after the procedure and more after 4 or 6 weeks with least complications

Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6–12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term Gemcitabine on the tumor microenvironment in order to identify potential therapeutic options for chemo-refractory PDAC. Using a combination of mouse models, primary cell line-derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, Gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFβ-associated signals. These secreted factors altered the composition of the tumor stroma, conferring Gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFβ1 biosynthesis. Combined Gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFβ signaling. In the setting of TGFβ signaling deficiency, Gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that Gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of Gemcitabine-refractory PDAC

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Peri-papillary retinal nerve fiber layer thickness profile in subjects with myopia measured using optical coherence tomography

Aims: To evaluate the effect of myopia on peri-papillary retinal nerve fiber layer (RNFL) thickness in various quadrants and clock hour positions. Also, to evaluate the effect of myopia on the location of superotemporal and inferotemporal peak positions of peri-papillary RNFL. Setting and Design: Observational cross-sectional study from November 2011 to March 2013. Myopic patients between age group of 20-30 years were evaluated by spectral domain optical coherence tomography (SD-OCT). Materials and Methods: Myopic eyes were classified into three groups based on refractive error - Group 1: myopia up to 3 D (Diopter, D), Group 2: myopia of 3-6 D, and Group 3: Myopia > 6 D. OCT scan was done to measure peri-papillary RNFL and to locate superotemporal and inferotemporal peak positions. Statistical Analysis Used: Data was analyzed using one way ANOVA and post hoc analysis using Tukey′s test. Results and Conclusion: A total of 118 myopic eyes were evaluated. Eyes in Group 3 show significant thinning in 360 degree average RNFL thickness and in all quadrants except temporal as compared to Group 1 and 2. Correspondingly, in eyes with myopia > 6 D (as compared to Group 1 and 2), decrease in RNFL thickness is seen in all clock hour positions except 4, 8, 9, and 10. Also, in high myopia (>6 D), there is a significant shift in inferotemporal RNFL peak to temporal side while no significant change is noticed in superotemporal RNFL peak when compared to Groups 1 and 2. No significant difference was noted between Groups 1 and 2 in RNFL thickness profile and RNFL peak positions. While analyzing RNFL thickness in subjects with highly myopic eyes, this difference in topographic profile of RNFL thickness should be taken into consideration

Sebaceous Carcinoma of the Eyelid

Sebaceous gland carcinoma of the eyelid is a very rare, slow growing tumor arising from the meibomian glands. In contrast to squamous cell carcinoma and basal cell carcinoma which arise frequently from the lower lid, sebaceous carcinoma arises from the upper lid where meibomian glands are more numerous. We present a case of sebaceous carcinoma in an elderly lady who presented with a slow growing tumor in the lateral third of the lower lid, without any lymp node metastasis. The tumor was treated by wide excision and the eyelid was reconstructed by Tenzel semilunar flap

Role of Outreach Camps in Reducing the Burden of Cataracts in South India

Aim: To establish the efficacy of rural outreach programme in reducing blindness caused by cataract by comparative analysis of visual outcome. Materials and Methods: Records of patients attending outreach camps conducted during 10 years i.e., 2001-02 to 2010-11 were studied. The total number of patients attending the camp and those who were detected to have visually significant cataract were noted. Similarly, the number of patients attending the outpatient department of the department of Ophthalmology and the number detected with visually significant cataract were noted. Data was tabulated and analyzed. Result: Out of 1, 16,615 patients visiting the outpatient department during those ten years, 3,014 were detected to have cataract (2.58%). 744 camps were conducted during the period of ten years, screening 60,086 patients and 6711 (11.17%) of them were detected to have cataract and were operated. These results were statistically significant. Conclusions: High numbers of cataracts were detected in the rural parts of South India with the help of outreach camps, while compared to tertiary care centres. They were given treatment in the form of cataract extraction and implantation of intraocular lens. Hence, conducting outreach camps forms an integral part in decreasing the visual morbidity due to cataract

Case series of central retinal artery occlusion in COVID-19-associated rhino-orbital-cerebral mucormycosis

Rhino orbital Mucormycosis caused by filamentous fungus of mucoraceae family was considered a rare disease affecting immunocompromised and diabetics with ketoacidosis until the recent COVID 19 pandemic. We are presenting a series of six cases of Rhino orbital cerebral Mucormycosis with central retinal artery occlusion. All six cases had common history of COVID 19 infection in recent past with sinusitis, proptosis and total ophthalmoplegia with central retinal artery occlusion on presentation. MR imaging showed invasive pan sinusitis with orbital and cerebral involvement. Urgent debridement was done and histopathological examination showed broad, filamentous aseptate fungi suggestive of Mucormycosis. All patients inspite of intravenous Amphotericin B with local debridement did not show any improvement and expired within a week of presentation. Hence our study shows poor prognosis of post covid 19 associated Mucormycosis with central retinal artery occlusion