Evaluation of the non-endoscopic and endoscopic-assisted platysma flap - A randomized control trial.

Background and Aim: As oral submucous fibrosis (OSMF) is a chronic progressive disorder, the treatment is based on the severity of the disease. Surgical treatment is the only choice for grade III and grade IV OSMF cases because the patient can neither clean his/her mouth nor properly chew. The resulting soft tissue defect requires resurfacing with various well-vascularized tissues such as extraoral flaps, intraoral flaps, microvascular flaps, and allografts that have been used. Reconstruction of the resultant defects proved to be challenging. Till date, none of the flaps has been proven to be effective and is universally accepted for the treatment of OSMF because of various drawbacks of the available techniques. This study was conducted to know whether an endoscopic-assisted platysma flap is associated with better outcomes in terms of ease of operation and postoperative function than the conventional approach. Materials and Methods: This study included 40 patients of grade III and grade IV OSMF reporting to the outpatient department of oral and maxillofacial surgery in a tertiary center of North India. These patients were divided randomly into two groups. Group I and Group II had 20 patients each, undergoing endoscopic-assisted platysma flap and non-endoscopic-assisted platysma flap for reconstruction after resection of OSMF bands, respectively. Data were analyzed for the mouth opening, operating time, flap viability, congestion of neck and oral cavity, signs of inflammation, neurologic assessment, and measurement of the drain. Results: The results showed significant increase in mouth opening from the preoperative value to the values immediately after surgery and at 24 h, 1 week, 15 days, 1 month, 3 months, and 6 months after surgery in both the study groups. Reduced bleeding incidence was found in group I compared to group II, with better postoperative outcomes noted during follow-up. But the mean intraoperative time of the subjects in group I was 130.80 ± 5.5.908 min and in group II was 105.74 ± 2. 491 min. Increased time taken in group I may be due to the long learning curve. Conclusion: The present study concluded that the Endoscope-assisted technique has a key role during supra and subplatysmal dissection to allow for better accessibility, handling, and visibility of the flap and its orientation in relation to the underlying structures to avoid postoperative complications and to overcome the drawback of platysma myocutaneous flap in reconstruction of OSMF defects.

Visual outcome and postoperative complications of cataract surgery in patients with ocular surface disorders.

PURPOSE: To determine the visual outcome and postoperative complications of cataract surgery in patients with ocular surface disorders (OSDs). SETTING: Tertiary eyecare center in North India. DESIGN: Retrospective observational study. METHODS: Patients with various OSDs with stabilized ocular surfaces who underwent cataract surgery during this period and had a minimum postoperative follow-up of 6 weeks were included. The primary outcome measures were postoperative corrected distance visual acuity (CDVA) at 6 weeks, best CDVA achieved, and postoperative complications. RESULTS: The study included 20 men and 24 women. A total of 55 eyes were evaluated: Stevens-Johnson syndrome (SJS) 35 eyes, ocular cicatricial pemphigoid (OCP) 4 eyes, 8 eyes with dry eye disease (DED), 6 eyes with chemical injury and 2 eyes with vernal keratoconjunctivitis (VKC). The mean duration of OSD was 33.9 ± 52.17 months. The median preoperative CDVA was 2.0 (interquartile range [IQR], 1.45 to 2.0). The median CDVA ever achieved was 0.50 (IQR, 0.18 to 1.45) at 2 months and the median CDVA at 6 weeks was 0.6 (IQR, 0.3 to 1.5). Maximum improvement in CDVA was noted in patients with DED and SJS and the least in OCP. Phacoemulsification was performed in 47.27% eyes with intraoperative complications noted in 9% eyes. Postoperative surface complications occurred in 12 (21.82%) eyes. Other postoperative complications occurred in 9 (16%) eyes. CONCLUSIONS: Cataract surgery outcome can be visually rewarding in patients with OSDs provided ocular surface integrity is adequately maintained preoperatively and postoperatively.

Combining fibril-induced alpha-synuclein aggregation and 6-hydroxydopamine in a mouse model of Parkinson's disease and the effect of cerebral dopamine neurotrophic factor on the induced neurodegeneration.

The existent pre-clinical models of Parkinson's disease do not simultaneously recapitulate severe degeneration of dopamine neurons and the occurrence of alpha-synuclein (aSyn) aggregation in one study system. In this study, we injected aSyn pre-formed fibrils (PFF) and 6-hydroxydopamine (6-OHDA) unilaterally into the striatum of C57BL/6 wild-type male mice at an interval of 2 weeks to induce aggregation of aSyn protein and trigger the loss of dopamine neurons simultaneously in one model and studied the behavioural effects of the combination in these mice. 6-OHDA was tested at three different doses, and 2 µg of 6-OHDA combined with PFF-induced aSyn aggregation was found to produce the most optimal disease phenotype. At 14 weeks timepoint, mice injected with a combination of PFF and 6-OHDA sustained significant damage to the nigrostriatal pathway and exhibited aSyn-positive aggregation. Our data suggest that the neurons that formed large aSyn aggregates were particularly vulnerable to 6-OHDA-induced degeneration. We also demonstrate the manifestation of a relatively aggressive pathology in 2- to 4-month-old mice, as compared to younger 7- to 9-week-old ones. Furthermore, cerebral dopamine neurotrophic factor (CDNF) administered intrastriatally rescued dopamine neurons and motor behaviour of the animals to some extent from 6-OHDA toxicity. However, no such effect could be seen in the novel 6-OHDA + PFFs combination model. For the first time, we demonstrate the combined effect of PFF and 6-OHDA simultaneously in one model. We further discuss the scope for further optimizing this combination model to develop it as a promising pre-clinical platform for drug screening and development.

Interleukin-11 Suppresses Ocular Surface Inflammation and Accelerates Wound Healing.

Purpose: Regulation of inflammation is critical for achieving favorable outcomes in wound healing. In this study, we determine the functional role and mechanism of action of IL-11, an immunomodulatory cytokine, in regulating inflammatory response at the ocular surface. Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma using an AlgerBrush II. Transcript and protein levels of IL-11 in injured cornea were quantified using real-time PCR and ELISA analysis. Corneal inflammation was assessed by measuring frequencies of total CD45+ inflammatory cells, CD11b+Ly6G+ polymorphonuclear cells (neutrophils), and CD11b+Ly6G- mononuclear cells (macrophages, monocytes) at the ocular surface using flow cytometry. To assess the effect of IL-11 on innate immune cell function, cell activation marker and inflammatory cytokines including major histocompatibility complex (MHC) class II, myeloperoxidase (MPO), TNFα, and inducible nitric oxide synthase (iNOS) were measured following recombinant IL-11 treatment (1 µg/mL). Injured corneas were topically treated with IL-11 (1 µg/mL), and wound healing was evaluated using corneal fluorescein staining. Results: Corneal injury resulted in increased levels of IL-11 in the cornea, particularly in the stroma. Neutrophils and CD11b+ mononuclear cells (macrophages, monocytes) substantially expressed IL-11 receptor. Interestingly, IL-11 significantly downregulated the activation of immune cells, as evidenced by the lower expression of MHC II and TNFα by CD11b+ mononuclear cells and lower levels of MPO by neutrophils. Topical administration of IL-11 to injured corneas led to faster wound healing and better retention of tissue architecture. Conclusions: Our findings demonstrate IL-11 is a key modulator of ocular surface inflammation and provide novel evidence of IL-11 as a potential therapeutic to control inflammatory damage and accelerate wound repair following injury.

Feasibility of combining alpha-synuclein aggregation and 6-OHDA in embryonic midbrain culture for modeling dopamine neuron degeneration.

Parkinson's disease (PD) is characterized by the loss of nigrostriatal dopamine (DA) neurons and the presence of alpha-synuclein (αSyn)-positive Lewy body (LB) pathology. In this study, we attempted to recapitulate both these features in a novel in vitro model for PD. To achieve this, we combined the αSyn pre-formed fibril (PFF)-seeded LB-like pathology with 6-hydroxydopamine (6-OHDA)-induced mitochondrial toxicity in mouse embryonic midbrain cultures. To pilot the model for therapeutics testing, we assessed the effects of cerebral dopamine neurotrophic factor (CDNF) on αSyn aggregation and neuron survival. PFF-seeded pathology did not lead to DA neuron loss even with the highest dose of PFFs. The combination of PFFs and 6-OHDA did not trigger additional neurodegeneration or LB-like pathology and instead presented DA neuron loss to a similar extent as with 6-OHDA only. CDNF did not affect the PFF-seeded αSyn pathology or the DA neuron survival in the combination model but showed a trend toward neuroprotection in the 6-OHDA-only cultures.

Increased activity of lacrimal gland mast cells are associated with corneal epitheliopathy in aged mice.

The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.

IL-36γ Augments Ocular Angiogenesis by Promoting the Vascular Endothelial Growth Factor-Vascular Endothelial Growth Factor Receptor Axis.

Prevention of inflammatory angiogenesis is critical for suppressing chronic inflammation and inhibiting inflammatory tissue damage. Angiogenesis is particularly detrimental to the cornea because pathologic growth of new blood vessels can lead to marked vision impairment and even loss of vision. The expression of proinflammatory cytokines by injured tissues exacerbates the inflammatory cascade, including angiogenesis. IL-36 cytokine, a subfamily of the IL-1 superfamily, consists of three proinflammatory agonists, IL-36α, IL-36ß, and IL-36γ, and an IL-36 receptor antagonist (IL-36Ra). Data from the current study indicate that human vascular endothelial cells constitutively expressed the cognate IL-36 receptor. The current investigation, for the first time, characterized the direct contribution of IL-36γ to various angiogenic processes. IL-36γ up-regulated the expression of vascular endothelial growth factors (VEGFs) and their receptors VEGFR2 and VEGFR3 by human vascular endothelial cells, suggesting that IL-36γ mediates the VEGF-VEGFR signaling by endothelial cells. Moreover, by using a naturally occurring antagonist IL-36Ra in a murine model of inflammatory angiogenesis, this study demonstrated that blockade of endogenous IL-36γ signaling results in significant retardation of inflammatory angiogenesis. The current investigation on the proangiogenic function of IL-36γ provides novel evidence of the development of IL-36γ-targeting strategies to hamper inflammatory angiogenesis.

Single-Staged Surgical Correction of Eyelid Sequelae Along With Lid Margin Mucous Membrane Grafting in Stevens-Johnson Syndrome and Other Cicatricial Ocular Surface Diseases.

PURPOSE: The purpose of this study was to study the outcome of single-staged entropion surgery along with lid margin mucous membrane grafting for cicatrizing ocular surface disease. METHODS: Retrospective review of medical records of patients who underwent single-staged surgical correction of cicatricial entropion along with lid margin mucous membrane grafting for lid margin keratinization. RESULTS: Twenty-six eyes of 19 patients were studied. The mean age of patients was 42.5 years (standard deviation, SD-17.67), of which 7 patients were male and 12 were female. The most common disorder was Stevens-Johnson syndrome (SJS) sequelae (83.33%, n = 20), followed by mucous membrane pemphigoid (n = 4, 16.67%). The most common eyelid changes observed were cicatricial entropion in all 26 eyes (100%, n = 26), followed by trichiasis in 13 eyes (50%, n = 13). Lid margin keratinization was noted in all eyes. Postoperative improvement in corneal surface staining was noted in 70% of the patients (n = 13), no change in 20% of the patients (n = 4), and worsening of corneal surface staining in 10% of the patients (n = 2). Postoperative visual acuity improvement was noted in 50% of the eyes (n = 13), no improvement in 39% of the eyes (n = 10), and vision worsened in 12% of the eyes (n = 3). An entropion recurrence rate of 25% (n = 6) was observed over an average 10-month follow-up, whereas 75% (n = 20) reported no recurrence. CONCLUSIONS: Single-staged correction of eyelid cicatricial entropion with a lid margin mucous membrane graft (MMG) has promising outcomes in ocular surface diseases. It can decrease the need for multiple surgeries and provide symptomatic relief in patients with chronic cicatricial surface changes.

Role of AS-OCT in Managing Corneal Disorders.

Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.

Trends and Resource Utilization in Kawasaki Disease Hospitalizations in the United States, 2008-2017.

OBJECTIVES: To explore trends in hospitalization rate, resource use, and outcomes of Kawasaki Disease (KD) in children in the United States from 2008 to 2017. METHODS: This was a retrospective, serial cross-sectional analysis of pediatric hospitalizations with International Classification of Disease diagnostic codes for KD in the National Inpatient Sample. Hospitalization rates per 100 000 populations were calculated and stratified by age group, gender, race, and US census region. Prevalence of coronary artery aneurysms (CAA) were expressed as proportions of KD hospitalizations. Resource use was defined in terms of length of stay and hospital cost. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for categorical and continuous variables, respectively. P <.05 was considered significant. RESULTS: A total of 43 028 pediatric hospitalizations identified with KD, yielding an overall hospitalization rate of 5.5 per 100 000 children. The overall KD hospitalization rate remained stable over the study period (P = .18). Although KD hospitalization rates differed by age group, gender, race, and census region, a significant increase was observed among Native Americans (P = .048). Rates of CAA among KD hospitalization increased from 2.4% to 6.8% (P = .04). Length of stay remained stable at 2 to 3 days, but inflation-adjusted hospital cost increased from $6819 in 2008 to $10 061 in 2017 (Ptrend < 0.001). CONCLUSIONS: Hospitalization-associated costs and rates of CAA diagnostic codes among KD hospitalizations increased, despite a stable KD hospitalization rate between 2008 and 2017. These findings warrant further investigation and confirmation with databases with granular clinical information.

Evaluation of dry eye symptoms in lecturers working in medical colleges of Nepal: An online cross-sectional study following SARS-CoV-2 outbreak.

INTRODUCTION: Dry eye is one of the frequently encountered ophthalmological disorders. Following the pandemic of Coronavirus disease 2019, use of masks and electronic devices has taken an upraise globally. These factors are one of the causes for dry eye disease. This study emphasises dry eye symptoms among lecturers working in medical colleges of Nepal. MATERIALS AND METHODS: This was a descriptive cross sectional study conducted among 217 lecturers working in various medical colleges in Nepal. Dry eye evaluation was done using the Ocular Surface Disease Index (OSDI) questionnaire. Analysis of data was using Microsoft Excel 2016 and IBM Statistical Package for Social Sciences (SPSS) version 26.0. RESULTS: One fourth (25.80%) of 217 participants experienced symptoms of dry eye disease. CONCLUSION: Increasing use of mask and laptop during this pandemic era has shown to cause mild dry eye symptoms in lecturers working in medical colleges of Nepal. Proper care and precaution needs to be practised in order to minimise dry eye symptoms and its consequences.

Economic, clinical and social impact of simple limbal epithelial transplantation for limbal stem cell deficiency.

AIMS: To report the global uptake of simple limbal epithelial transplantation (SLET) and compare the economic, clinical and social outcomes of SLET with those of cultured limbal epithelial transplantation (CLET). METHODS: A comprehensive literature review and an online survey of eye surgeons were conducted to understand the efficacy and current uptake of SLET surgery. A de novo economic model was developed to estimate the cost savings with SLET compared with CLET. Our economic analysis is conducted from an Indian perspective, as this is where the technique originated. A scenario analysis using the UK cost data and a user-friendly Excel model is included to allow users to input the costs from their setting to estimate the cost savings with using SLET compared with using CLET RESULTS: The anatomical success with SLET in adults (72.6% (range 62%-80%)) was the same as CLET (70.4% (range 68%-80.9%)). For children, the outcome for SLET (77.8% (range 73%-83%)) was better than with CLET (44.5% (range 43%-45%)). In response to our informal questionnaire, 99 surgeons reported to have performed SLET on 1174 patients in total. They appreciated that SLET negates the requirement for costly tissue engineering facilities. Results of economic analysis suggested that SLET provided an estimated cost-savings of US$6470.88 for adults and US$6673.10 for children. In broad terms, the cost of SLET is approximately 10% of the cost of CLET for adults and 8% for children. CONCLUSION: SLET offers a more accessible and financially attractive alternative to CLET to treat limbal stem cell deficiency.

Actin-related protein 4: An unconventional negative regulator of mitochondrial calcium in protozoan parasite Leishmania.

Regulation of mitochondrial calcium import is less understood in evolutionarily distinct protozoan parasites, such as Leishmania, as some of the mitochondrial calcium uniporter complex proteins are either missing or functionally diverged. Here, we show that Actin-related protein4 (ARP4), localizes exclusively into the Leishmania mitochondrion and depletion of this protein causes cells to accumulate calcium in the mitochondrion. The ARP4 depleted cells show increased activation of pyruvate dehydrogenase and production of ATP. Overall, our results indicate that ARP4 negatively regulates calcium uptake in the Leishmania mitochondrion.

Infectious Keratitis: An Update on Role of Epigenetics.

Epigenetic mechanisms modulate gene expression and function without altering the base sequence of DNA. These reversible, heritable, and environment-influenced mechanisms generate various cell types during development and orchestrate the cellular responses to external stimuli by regulating the expression of genome. Also, the epigenetic modifications influence common pathological and physiological responses including inflammation, ischemia, neoplasia, aging and neurodegeneration etc. In recent past, the field of epigenetics has gained momentum and become an increasingly important area of biomedical research As far as eye is concerned, epigenetic mechanisms may play an important role in many complex diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. Focusing on the epigenetic mechanisms in ocular diseases may provide new understanding and insights into the pathogenesis of complex eye diseases and thus can aid in the development of novel treatments for these diseases. In the present review, we summarize the clinical perspective of infectious keratitis, role of epigenetics in infectious keratitis, therapeutic potential of epigenetic modifiers and the future perspective.

Structural insights into kinetoplastid coronin oligomerization domain and F-actin interaction.

The two-domain actin associated protein coronin interacts with filamentous (F-) actin, facilitating diverse biological processes including cell proliferation, motility, phagocytosis, host-parasite interaction and cargo binding. The conserved N-terminal ß-propeller domain is involved in protein: protein interactions, while the C-terminal coiled-coil domain mediates oligomerization, transducing conformational changes. The L. donovani coronin coiled-coil (LdCoroCC) domain exhibited a novel topology and oligomer association with an inherent asymmetry, caused primarily by three a residues of successive heptads. In the T.brucei homolog (TbrCoro), two of these 'a' residues are different (Val 493 & 507 replacing LdCoroCC Ile 486 and Met 500 respectively). The elucidated structure possesses a similar topology and assembly while comparative structural analysis shows that the T.brucei coronin coiled-coil domain (TbrCoroCC) too possesses the asymmetry though its magnitude is smaller. Analysis identifies that the asymmetric state is stabilized via cyclic salt bridges formed by Arg 497 and Glu 504. Co-localization studies (LdCoro, TbrCoro and corresponding mutant coiled coil constructs) with actin show that there are subtle differences in their binding patterns, with the double mutant V493I-V507M showing maximal effect. None of the constructs have an effect on F-actin length. Taken together with LdCoroCC, we therefore conclude that the inherent asymmetric structures are essential for kinetoplastids, and are of interest in understanding and exploiting actin dynamics.

Mini Review: Current Trends and Understanding of Exosome Therapeutic Potential in Corneal Diseases.

Exosomes are a subset of extracellular vesicles (EVs) that are secreted by most cell types. They are nanosized EVs ranging from 30 to 150 nm. The membrane-enclosed bodies originate by the process of endocytosis and mainly comprise DNA, RNA, protein, and lipids. Exosomes not only act as cell-to-cell communication signaling mediators but also have the potential to act as biomarkers for clinical application and as a promising carrier for drug delivery. Unfortunately, the purification methods for exosomes remain an obstacle. While most of the exosome researches are mainly focused on cancer, there are limited studies highlighting the importance of exosomes in ocular biology, specifically cornea-associated pathologies. Here, we summarize a brief description of exosome biogenesis, roles of exosomes and exosome-based therapies in corneal pathologies, and exosome bioengineering for tissue-specific therapy.