Comparison of Clinical Characteristics and Biomarkers in Culture-Positive and Culture-Negative Sepsis Patients.

OBJECTIVES: Sepsis is one of the leading causes of morbidity and mortality worldwide, and culture-negative sepsis, despite its prevalence, is largely understudied. The current study intends to examine clinical characteristics and biomarkers in culture-positive and culture-negative sepsis, focusing on 30-day mortality and duration of hospital stay in both groups.  Materials and methods: A prospective observational comparative cohort study was done on 150 patients admitted to the intensive care unit (ICU) and wards of Jaipur Golden Hospital. Patients with documented fungal, viral, or parasitic infections, as well as those who had undergone surgery or experienced trauma, were excluded.  Results: The mean age of the patients was 51.31±18.94 years. Of 150 patients, 95 (63.3%) were culture-negative, whereas 55 (36.7%) were culture-positive, with more men in the former and more women in the latter. Patients with negative cultures had fewer comorbidities. The levels of procalcitonin (PCT), C-reactive protein (CRP), and serum lactate were within the prescribed limit for both culture-negative and positive patients. A higher proportion (87.3%) of the organisms isolated from culture-positive individuals were gram-negative, with Escherichia coli (E. coli) having the highest prevalence (27.3%), followed by Klebsiella (20%). There were 12.7% gram-positive isolates. The culture-negative patients had significantly better outcomes (P=0.003) as well as the duration of hospital stay (P<0.001) than the culture-positive patients. Culture-positive patients had a more severe illness, a higher incidence of septic shock, and a higher fatality rate than culture-negative patients. CONCLUSION: It can be concluded that CRP and PCT can be used as clinically reliable sepsis biomarkers in both culture-positive and culture-negative patients. The study found that culture-negative sepsis is more prevalent and that there are substantial differences between culture-negative and culture-positive sepsis, with the former group having fewer comorbidities, less severe illness, a shorter duration of hospital stays, lower death rates, and better outcomes.

Concurrence of Ocular Cicatricial Pemphigoid in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The aim of this study was to report a series of 3 patients with ocular graft-versus-host disease (oGVHD) with progressive cicatricial conjunctival changes who were diagnosed with ocular cicatricial pemphigoid (OCP) after conjunctival biopsy. METHODS: This study was a retrospective case series. RESULTS: Three patients who received hematopoietic stem cell transplantation for hematologic malignancies developed oGVHD and subsequently were diagnosed with OCP. Case 1 was a 73-year-old woman with oGVHD who developed symblepharon and showed positive IgA, IgG, and C3 staining of the basement membrane zone (BMZ) on conjunctival biopsy, consistent with OCP. She was systemically treated with tacrolimus and prednisone with resolution of conjunctival inflammation. Case 2 was a 68-year-old man with oGVHD who developed symblepharon, severe dry eye, and corneal epithelial defect. An initial conjunctival biopsy was negative, but a repeat biopsy performed 10 years later showed positive BMZ IgA and IgG staining. Healing of the epithelial defect was achieved after treatment with high-dose systemic cyclosporine. Case 3 was a 75-year-old woman with oGVHD who had a nonhealing corneal epithelial defect and symblepharon with positive IgA BMZ staining on conjunctival biopsy, consistent with OCP. The patient responded well to methotrexate with healing of the epithelial defect. CONCLUSIONS: Although low-grade conjunctival fibrotic changes may be observed in chronic oGVHD, development of severe and progressive cicatricial changes, including symblepharon formation, should prompt consideration of biopsy to rule out concurrent OCP, the management of which differs from that of oGVHD.

Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.

Existing therapeutic interventions for controlling cancer are limited and associated with side effects. Furthermore, the recurrence of cancer poses a significant challenge to the cure of cancer. Therefore, avenues are wanted to find novel therapies for cancer treatment and cancer recurrence. In this review, we have highlighted that lactoferrin (LF) and activated protein C (APC) carry enormous potential in cancer treatment. Studies have shown that the decreased level of APC and impaired function of APC are associated with cancer progression and cancer-related mortality. Moreover, APC plays an important role in preventing prothrombotic state-mediated cancer progression and deaths. LF can also inhibit the progression of cancer by controlling the generation of reactive oxygen species, triggering the apoptosis of cancer cells, arresting the cell cycle and hindering the angiogenesis process. Additionally, APC and LF could have the potential to inhibit neutrophil extracellular traps (NETs) formations which are involved in cancer progression and the reawakening of dormant cancer cells. Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.

Emerging Field of Nanotechnology in Environment.

The art of utilizing and manipulating micro materials have been dated back to antient era. With the advancement in technologies, the state-of-art methods of nano technologies and nano sciences has been employed in various sectors including environment, product designing, food industry, pharmaceuticals industries to way out solve standard problem of mankind. Due to rapid industrialization and the alarming levels of pollution there has been an urgent need to address the environmental and energy issues. Environmental sustainability concerns the global climate change and pollution including air, water, soil. The field of nanotechnology has proven to be a promising field where sensing and remediation, have been dramatically advanced by the use of nanomaterials. This emergent science of surface to mass ratio is the principle theorem for manipulating structure at molecular levels. The review sums up all the advancements in the field of nanotechnology and their recent application in the environment. New opportunities and challenges have also been discussed in detail to understand the use of nanotechnology as problem-to-solution ratio. Graphical abstract: Image depicting the application of nanotechnology in environmental concerns. The combinations of technologies like bioremediations, bioaugmentations with state-of-the-art nanotechnology like carbon nanotubes and Nano capsules to answer the environmental challenges of soil quality, and plant productivity.

Reactivation of retinopathy of prematurity six years after intravitreal injection of bevacizumab.

Although intravitreal anti-vascular endothelial growth factor (VEGF) therapy is effective in the management of retinopathy of prematurity (ROP), reactivations following treatment are known to occur. We present the case of an asymptomatic child who developed a very late reactivation of ROP 6 years after its successful treatment with intravitreal bevacizumab. This case reemphasizes the importance of long-term follow-up after anti-VEGF therapy for ROP until retinal vascularization is complete. It also supports investigating the utility of laser photocoagulation for peripheral avascular retina after successful treatment with anti-VEGF injection for type I ROP.

Ocular complications of plasma cell dyscrasias.

Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.

Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials.

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.

Factors associated with appointment 'no-shows' at two tertiary level outpatient oculoplastic clinics.

PURPOSE: Appointment no-shows in clinics can adversely impact patients and physicians alike. This study aimed to determine the rate and potential causes of missed appointments in oculoplastic clinics and compare a private practice and hospital-based academic setting. METHODS: A retrospective review of patients who booked appointments for oculoplastic consultation, between August 2019 and January 2020 at two oculoplastic clinics was performed. Demographic and patient-specific characteristics of patients who failed to attend their appointment were identified. Data were analysed to determine and compare the no-show rates in both clinics and logistic regression was performed to determine factors associated with them. RESULTS: The rate of missed appointments was 3% and 17% at the oculoplastic clinics of Lions Eye Institute (LEI, private practice) and Albany Medical Center (AMC, academic hospital-based office), respectively. Patients at the AMC clinic were more likely to be male, younger, have a lower household income, not carry private insurance, and suffer from trauma. Logistic regression analysis showed lower patient age to significantly increase the likelihood of no-shows in both clinics (p = .01 for LEI, p = .003 for AMC), and lead appointment time greater than 90 days to be a significant risk factor for no-shows at LEI (p = .01). CONCLUSIONS: The no-show rate for oculoplastic appointments is 3% and 17% at LEI and AMC clinics, respectively. Our analysis shows that younger patients are more likely to miss appointments at both clinics, and an appointment lead time greater than 90 days is a significant risk factor for no-shows at LEI.

Statistical evaluation and positive predictive value of key features of periorbital basal cell carcinoma.

OBJECTIVE: To determine the accuracy of using the suspicious features of periorbital lesions-telangiectasias, madarosis, and ulceration-to identify basal cell carcinoma (BCC). This may impact whether a histopathologic confirmation is always necessary. METHODS: This retrospective review of patients who underwent biopsy of eyelid lesions was conducted over a five-year period, between 2015 and 2020 at a single clinical site. Specifically, the histopathologic diagnosis and the presence or absence of clinical signs of madarosis, ulceration and telangiectasia were recorded. The positive predictive value (PPV) for eyelid BCC and odds ratio of each of these clinical signs was calculated. RESULTS: 179 patients underwent incisional biopsies of eye lid lesions. Of the 79 patients with eyelid BCC, 96% had ulceration, 95% had madarosis, and 75% had telangiectasias over the lid lesion; this contrasted with the 3%, 4% and 6% respectively in the 100 patients with benign lid lesions. The PPV for eyelid BCC of ulceration was 95.0%, madarosis was 96.2% and telangiectasias was 90.8%. The presence of two or all three signs in a patient was strongly predictive of BCC (PPV=100%). CONCLUSION: The presence of two or more suspicious features almost ensures the accuracy of the suspected diagnosis of a BCC. This suggests that biopsy of eyelid lesions before complete surgical excision that demonstrate several defining features may not be necessary in all cases. However, lesions that do not demonstrate multiple explicit features that indicate a malignancy will still require histopathologic confirmation.

Ocular pain in ocular graft-versus-host disease patients with neurotrophic keratopathy.

PURPOSE: Neurotrophic keratopathy (NK) is a degenerative disorder of the cornea characterized by decreased sensory innervation, epitheliopathy, and impaired epithelial healing. In this study, we assessed ocular pain and quality-of-life-related parameters in ocular graft-versus-host disease (oGVHD) patients with and without NK. METHODS: We included 213 oGVHD patients in this retrospective study, including 29 patients with NK assessed by the Cochet-Bonnet esthesiometer. We evaluated their records for ocular pain assessment survey (OPAS) scores and clinical parameters, including corneal sensation, corneal fluorescein staining (CFS) score, Schirmer's test, tear break-up time (TBUT), and ocular surface disease index (OSDI) score. RESULTS: oGVHD patients with NK had lower corneal sensation (3.4 ± 1.4 vs. 5.9 ± 0.3; p < 0.0001), higher CFS scores (6.4 ± 4.2 vs. 4.7 ± 4.0; p = 0.01), and lower TBUT scores (1.2 ± 2.1 vs. 2.2 ± 3.1; p = 0.08) compared to oGVHD patients without NK and additionally had significantly higher ocular pain intensity scores (OPAS 24-h average eye pain intensity: 2.0 ± 2.8 vs. 1.1 ± 1.9; p = 0.03). Patients with NK more commonly reported burning (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.021) and sensitivity to light (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.049) as compared to patients without NK. CONCLUSION: Clinical signs of ocular surface disease are worse in oGVHD patients with NK compared to oGVHD patients without NK. These patients additionally experience higher intensity ocular pain and lower quality-of-life-related parameters.

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease.

PURPOSE: To determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD). DESIGN: Retrospective cohort study. METHODS: We performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients. MAIN OUTCOME MEASURE: Prevalence of NK in chronic oGVHD. RESULTS: We identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients. CONCLUSIONS: The prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.

Development of miniaturized agar based assays in 96-well microplates applicable to high-throughput screening of industrially valuable microorganisms.

High-throughput screening (HTS) is a present-day approach for assaying thousands of cultures in parallel. This miniaturization allows rapid screening of large number of microorganims capable of producing bio-based materials thereby meeting the demands of the ever evolving food, pharmaceutical and cosmetic industry. In this study, agar-based assays for phosphate solubilization, cellulose degradation and lactic acid production were developed in 96-well microplates using Biomek FXP Automated Liquid Handling system. Techno-economic analysis from this study reveals the lower overall cost per assay using HTS as compared to conventional Petri plate assays. Though automated liquid handling workstations have been used to perform liquid-based assays, there are very few studies which report their use for agar-based microplate assays. These findings thus corroborate the establishment of rapid and efficient miniaturized, qualitative agar-based screening methods for identifying microorganisms with potential for commercial application.

Type-I Interferon Signaling in Fanconi Anemia.

Fanconi Anemia (FA) is a genome instability syndrome caused by mutations in one of the 23 repair genes of the Fanconi pathway. This heterogenous disease is usually characterized by congenital abnormalities, premature ageing and bone marrow failure. FA patients also show a high predisposition to hematological and solid cancers. The Fanconi pathway ensures the repair of interstrand crosslinks (ICLs) DNA damage. Defect in one of its proteins prevents functional DNA repair, leading to the accumulation of DNA breaks and genome instability. Accumulating evidence has documented a close relationship between genome instability and inflammation, including the production of type-I Interferon. In this context, type-I Interferon is produced upon activation of pattern recognition receptors by nucleic acids including by the cyclic GMP-AMP synthase (cGAS) that detects DNA. In mouse models of diseases displaying genome instability, type-I Interferon response is responsible for an important part of the pathological symptoms, including premature aging, short stature, and neurodegeneration. This is illustrated in mouse models of Ataxia-telangiectasia and Aicardi-Goutières Syndrome in which genetic depletion of either Interferon Receptor IFNAR, cGAS or STING relieves pathological symptoms. FA is also a genetic instability syndrome with symptoms such as premature aging and predisposition to cancer. In this review we will focus on the different molecular mechanisms potentially leading to type-I Interferon activation. A better understanding of the molecular mechanisms engaging type-I Interferon signaling in FA may ultimately lead to the discovery of new therapeutic targets to rescue the pathological inflammation and premature aging associated with Fanconi Anemia.

LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion.

How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.

Wall eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome as a false localising sign in intracranial haemorrhage due to snake bite.

A 48-year-old woman presented with sudden-onset altered sensorium 2 days after a snake bite (unidentified species) and was found to have a large right frontal intracerebral haemorrhage (ICH) with transtentorial herniation (TTH) causing brain stem compression. A day later, neurological examination revealed internuclear ophthalmoplegia (INO) fitting the clinical description of wall eyed bilateral INO syndrome. INO is a rare ocular motor sign, the most common causes being brain stem infarction, haemorrhage or demyelinating disease. It rarely acts as a false localising sign, such as in this case, and in an even rarer cause for ICH, that is, haemotoxic snake bite without initial evidence of coagulopathy. An emphasis needs to be laid on detailed physical examination, often considered a lost art nowadays, to help detect subtle clinical signs which could herald ominous complications of conditions like TTH and help in early diagnosis and treatment of the same.

Generation of a tissue-specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo.

Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas (SCCs), where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by posttranslational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Even though deregulation of K8 phosphorylation at two significant sites (Serine73 /Serine431 ) has been implicated in neoplastic progression of SCCs by various in vitro studies, including ours, it is reported to be highly context-dependent. Therefore, to delineate the precise role of Kereatin 8 phosphorylation in cancer initiation and progression, we have developed the tissue-specific transgenic mouse model expressing Keratin 8 wild type and phosphodead mutants under Keratin 14 promoter. Subjecting these mice to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-mediated skin carcinogenesis revealed that Keratin 8 phosphorylation may lead to an early onset of tumors compared to Keratin 8 wild-type expressing mice. Conclusively, the transgenic mouse model developed in the present study ascertained a positive impact of Keratin 8 phosphorylation on the neoplastic transformation of skin-squamous cells.

Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants.

BACKGROUND: Preterm birth affects almost 9-11% of newborns and is one of the leading causes of childhood neurodevelopmental disabilities; the underlying molecular networks are poorly defined. In neurons, retrotransposons LINE-1 (L1) are an active source of genomic mosaicism that is deregulated in several neurological disorders; early life experience has been shown to regulate L1 activity in mice. METHODS: Very preterm infants were randomized to receive standard care or early intervention. L1 methylation was measured at birth and at hospital discharge. At 12 and 36 months, infants' neurodevelopment was evaluated with the Griffiths Scales. L1 methylation and CNVs were measured in mouse brain areas at embryonic and postnatal stages. RESULTS: Here we report that L1 promoter is hypomethylated in preterm infants at birth and that an early intervention program, based on enhanced maternal care and positive multisensory stimulation, restores L1 methylation levels comparable to healthy newborns and ameliorates neurodevelopment in childhood. We further show that L1 activity is fine-tuned in the perinatal mouse brain, suggesting a sensitive and vulnerable window for the L1 epigenetic setting. CONCLUSIONS: Our results open the field on the inspection of L1 activity as a novel molecular and predictive approach to infants' prematurity-related neurodevelopmental outcomes. TRIAL REGISTRATION: ClinicalTrial.gov ( NCT02983513 ). Registered on 6 December 2016, retrospectively registered.

How Important Is to Know the Psychosocial Performance in an Operated Child of Meningioma? Devil Is in the Details.

BACKGROUND: Meningioma constitutes only 0.4%-4.1% of all the pediatric tumors. This article aims to find the impact of the pediatric meningioma surgery on the developmental and scholastic performance among these children over long-term follow-up. MATERIALS AND METHODS: This study is a retrospective analysis of all the histopathological proven pediatric meningioma and a cross-sectional analysis to study the functional outcome, using Malin's Intelligence Scale for Indian children (MISIC); scholastic performance was assessed from behavioral checklist for screening the learning disabled (BCSLD) and subjective self-filled questionnaire to know parent satisfaction. RESULTS: Twenty-eight patients (mean age 14.52 ± 0.722 years) (M:F = 16:12) were analyzed (6 [21.4%] were grade-schooler and 22 [78.5%] were teenage), with most common symptom being headache (n = 20, 71.4%) and mean duration of symptoms was 11.19 ± 16.25 days. The mean intelligent quotient (IQ) of grade-schooler was 83.4 ± 9.072 compared to 75.69 ± 9.903 among teenage group. The BCSLD analyses showed that the postoperative score was poorer. Similarly, an average change in BCSLD was observed among the patients with complications (10) compared to the patients without complication (8). CONCLUSION: The discontinuation in schooling or lack of alternative education may lead to poor MISIC scores, wrongly categorizing the children in poor IQ group. In pediatric benign disease such as meningioma, the holistic approach should be opted from the time of first visit to neurological care team.

Prevalence and Risk Factors Associated With Corneal Perforation in Chronic Ocular Graft-Versus-Host-Disease.

PURPOSE: To determine the prevalence and risk factors associated with corneal perforation in patients with chronic ocular graft-versus-host disease (oGVHD). METHODS: We reviewed the case records of 405 patients diagnosed with chronic oGVHD over 8 years at a single academic center and assessed the prevalence of corneal perforation in the cohort. We reviewed patient demographics, indication for and type of hematopoietic stem cell transplantation (HSCT), time elapsed between HSCT and perforation, and clinical characteristics including oGVHD severity scores, ocular comorbidities, and topical medications at the time of perforation. Data were analyzed to determine the characteristics of patients with corneal perforation and establish the risk factors. RESULTS: Of the 405 patients with chronic oGVHD, 15 (3.7%) developed a corneal perforation. The mean age of patients at the time of perforation was 64 ± 11 years and 10 (67%) were men. The median time to corneal perforation was 3.3 years post-HSCT. Although perforation occurred unilaterally in all cases, 44% had epithelial defects and 38% had stromal abnormalities in the contralateral eye. Of the patients with corneal perforation, 9 (60%) had a National Institute of Health oGVHD severity score of 2 and 6 (40%) had a score of 3. Patients with chronic oGVHD on antiglaucoma drops had a significantly higher risk of corneal perforation (P < 0.001). CONCLUSIONS: Corneal perforation is a rare but vision-threatening complication of chronic oGVHD. Our study emphasizes the need for frequent and long-term follow-up of patients with oGVHD regardless of the severity of disease. In particular, patients with chronic oGVHD on topical antiglaucoma medications should be monitored closely due to a higher risk for corneal perforation.

Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab Injection for Treatment of Non-Proliferative Diabetic Macular Edema: A Prospective, Randomized and Blinded Trial.

INTRODUCTION: In the working age population, Diabetic Macular Edema (DME) is the most common cause of visual loss. PURPOSE: The present study is aimed to assess the safety and efficacy of intravitreal injection of Ranibizumab (IVR) versus intravitreal Dexamethasone implant (IVD) in patients with DME in a tertiary care centre upto 4 months. METHODS: This is a comparative, prospective, randomized study that was done on 140 patients with macular edema confirmed on optical coherence tomography (OCT). IVD group received Ozurdex® (Allergan, Inc, Ireland) while the IVR group received Lucentis® (Novartis, Basel, Switzerland); the groups were followed up at day-1 and weeks 4, 8, 12, 16. Patients were divided into Group A, in which patients were given 3 doses (monthly) of IVR 0.3 mg in 0.05 ml (n=70). Group B patients were given a single dose of IVD implant 0.7 mg (n=70). RESULTS: The mean number of injections given was 1 Ozurdex® per patient vs. 3 Lucentis® per patient. The maximum reduction in central macular thickness (CMT) with IVD was 167.8 µm and 138.8µm in the 2nd and 3rd months, respectively, with IVR. The mean best-corrected visual acuity (BCVA) in the 4th month was 0.34 logMAR and 0.33 logMAR, in IVD and IVR groups, respectively, with consistent improvement. Patients with 0-5 letters, 6-10 letters and 10-15 letters, and >15 letters visibility in IVD group were 9.5, 20.6, 4.8, 6.4%, and 20.4, 18.8, 20.3 20.3% in IVR groups, respectively. The maximum intraocular pressure (IOP) rise with IVD was found to be 16 mmHg in 2 patients (3.17%). IOP rise >10 mmHg was observed in 14/63 patients (22.22%); the majority of patients indicated a high rise at 2nd month with all returning to baseline by 4th month. No reports of infectious endophthalmitis or new cataracts were detected in either of the treated groups. CONCLUSION: Both intravitreal Ranibizumab injection and Dexamethasone implants were found to be safe and effective in lowering CMT and improving BCVA at the 4-month follow up in patients with DME. Since there was no recurrence of CMT in the Dexamethasone implant group, we suggest that early administration before the 4th month may indicate superior efficacy over the ranibizumab injection. Further randomized trials in a large sample size with a longer period follow- up would be performed to justify the obtained results in the present study.