Unveiling the Innate and Adaptive Immunity Interplay: Global Transcriptomic Profiling of the Host Immune Response in Candida albicans Endophthalmitis in a Murine Model.

Intraocular fungal infection poses a significant clinical challenge characterized by chronic inflammation along with vision impairment. Understanding the host defense pathways involved in fungal endophthalmitis will play a pivotal role in identifying adjuvant immunotherapy. Clinical isolates of Candida albicans (15,000 CFU/µL) were intravitreally injected in C57BL/6 mice followed by enucleation at 24 and 72 h postinfection. Histopathological analysis was performed to evaluate the retinal changes and the disease severity. RNA-seq analysis was conducted on homogenized eyeballs to assess the relevant gene profiles and their differentially expressed genes (DEGs). Pathway enrichment analysis was performed to further annotate the functions of the DEGs. Histopathological analysis demonstrated a higher disease severity with increased inflammatory cells at 72 hpi and transcriptome analysis revealed 27,717 DEGs, of which 1493 were significant (adj p value ≤0.05, FC ≥ 1.5). Among these, 924 were upregulated, and 569 were downregulated. Majority of the upregulated genes were associated with the inflammatory/host immune response and signal transduction and enriched in the T-cell signaling pathway, natural killer cell-mediated cytotoxicity, C-type receptor signaling pathway, and NOD-like receptor signaling pathway. Furthermore, inflammation-associated genes such as T-cell surface glycoprotein CD3, cathelicidin antimicrobial peptide, and lymphocyte cell-specific protein tyrosine kinase were enriched, while pathways such as MAPK, cAMP, and metabolic pathways were downregulated. Regulating the T-cell influx could be a potential strategy to modulate excessive inflammation in the retina and could potentially aid in better vision recovery in fungal endophthalmitis.

Optimization of Magnetic Behaviors of Au-NP-Decorated MWCNTs and Reduced Graphene Oxide for Biomedical Applications.

Optimization of electronic/magnetic behaviors of chemically decorated diamagnetic noble-metal gold nanoparticles (Au-NPs ≈5 at. %) on multiwalled carbon nanotubes (MWCNTs) and reduced graphene oxide (r-GO) is studied for future uses of optoelectronic/magnetic and biomedical applications. The changes between Au 4f5/2 and Au 4f7/2 ≈ 3.7 eV in X-ray photoelectron spectroscopy and 1.1 (±0.3) eV shifts in the C K-edge in X-ray absorption near edge structure spectroscopy confirm that the reduced form of Au0 was present in the Au-NP-decorated nanocomposites. The potential difference (ΔV) is built due to charge creations at the interface of r-GO/MWCNTs and Au-NPs and shifts in the Fermi level (ΔE F) due to electronic transfer effects, and as a result, the work functions are reduced from 3.2 eV (MWCNTs) to 3.0 eV (MWCNTs:Au-NPs) and 3.1 (r-GO) to 2.8 eV (r-GO:Au-NPS), respectively. Negligible remanence/coercivity in MWCNTs/r-GO (/Au-NPs) with blocking temperature ≈300 K in MWCNTs:Au-NPs accounted for the existence of diamagnetic Au-NPs in these nanocomposites, which implies a superparamagnetic nature. These results furnish the evidence about the optimization of magnetic behaviors of r-GO/MWCNTs (/Au-NPs) that may possibly be altered as a novel contrast agent for clinical magnetic resonance imaging, drug delivery, and hyperthermia applications.

Possible ferro-electro-magnetic behaviours of graphene-based materials: hydrogenated graphene, MWCNTs and reduced graphene-oxide (GO).

This study investigated the electric polarization and magnetic behaviours of various graphene-based materials, including hydrogenated graphene (H-graphene), multi-wall carbon nanotubes (MWCNTs), and reduced graphene oxide (r-GO). Results showed that MWCNTs exhibit higher magnetization, with a magnetic squareness (M r/M s) of approximately ≈0.5, compared to H-graphene (≈0.25). H-graphene exhibits the highest electric polarization compared to MWCNTs/r-GO, whereas r-GO demonstrates the lowest levels of polarization and magnetization compared to H-graphene/MWCNTs. The valence band maximum (4.08 eV for MWCNTs, 4.26 eV for H-graphene, and 4.78 eV for r-GO) in quasi-localized states at the Fermi level results in defects in the graphene-based lattice, which are associated with dipole moment and lead to alterations in magnetic behaviours. Different density of states (DOS) is attributed from the ultra-violet photoelectron spectra and the small variations in the Fermi edge is observed in H-graphene, MWCNTs, and r-GO are responsible for the observed magnetisation and polarizations. The unique polarization/magnetization behaviours present an opportunity for potential exploitation in storage and information processing technologies in the science and engineering community.

Infectious crystalline keratopathy-clinical-microbiological profile and outcome of management.

PURPOSE: To describe the clinical features, management, and long-term outcome of Infectious crystalline keratopathy (ICK). METHODS: The medical records of clinically diagnosed and microbiologically proven cases of ICK were reviewed from January 2011 to December 2022. Clinical characteristics include the presence of whitish needle-like projections with branching, limited to anterior-mid stroma. Keratoplasty being the most common risk factor, graft-related microbial keratitis during the same period was also studied. The demography, clinical profile, microbiology, treatment, and outcome were analyzed, and compared with secondary graft infiltrate(GI). RESULTS: Medical records of 24 cases with ICK were reviewed. The mean age was 49.3 ± 20.1 years, with 15(62.5%) males. Prior keratoplasty was done in 18 (75%) cases, with a mean graft size of 10.1 ± 1.5 mm, and mean interval between the last graft and presentation was 9.7 ± 6.2 (3-90) months. In comparison to GI (n = 24), ICK patients (n = 18,75%) were less symptomatic, presented late (7.3 ± 6.5 days vs 16.3 ± 19.4, p = 0.003), using frequent topical steroids (> 3 times/day, p = 0.006), smaller infiltrate size < 4 mm (p = 0.008), central (p = 0.02), less associated with epithelial defect (p = 0.0001), hypopyon (p = of 0.0002), corneal perforation (p = 0.0006), and surgical management (p = 0.03). On microbiology, 22 (91.6%) ICK cases were culture positive, 14 (63.6%) gram-positive, 3 (13.6%) gram-negative, 2 (9%) mixed bacteria, and 3 (13.6%) fungus, comparable with GI. CONCLUSION: ICK affects poor ocular surfaces usually following keratoplasty with larger graft size, the use of steroids being the most common association, and it responds to medical management as compared to GI.

Fibroblastic tumour in the medial rectus muscle presenting as a large-angle exotropia.

Objective: The aim is to report a very rare case of a fibroblastic tumour in the medial rectus muscle of the right eye in a young adult. Methods: A 28-year-old patient presented to the strabismus clinic with large-angle exotropia in the right eye. The patient had previously undergone strabismus surgery in both eyes, and the old photos showed increasing exotropia from childhood to adulthood. On examination, the patient had a best corrected visual acuity of 20/20, 85 PD of exotropia with a -4 limitation of adduction, and retinal evaluation was unremarkable. In view of the chronicity of the deviation, increasing exotropia over time, and limitation of the ocular motility in adduction, a magnetic resonance imaging was performed. Results: Orbital magnetic resonance imaging (MRI) undertaken to identify the extraocular muscle position revealed a bulky and thickened right medial rectus muscle with post-contrast enhancement and without fat stranding and orbital extension. A muscle biopsy was performed, and a series of histopathological stains revealed that the tumour cells were positive for CD34 and vimentin. Immuno histochemistry and histopathology suggested a benign fibroblastic tumour (superficial CD34+ fibroblastic tumour) with low malignant potential. Conclusion: This report describes a fibroblastic tumour of the eye muscle identified on neuroimaging and confirmed on histopathology. Such a presentation is very rare and to the best of our knowledge has not been previously reported in ophthalmic literature.

Repeat Femtosecond-Assisted Anterior Lamellar Keratoplasty for Recurrence of TGF B I Dystrophy in Eyes After Previous FALK.

PURPOSE: To report the management of recurrent TGF BI dystrophy after prior femtosecond-assisted anterior lamellar keratoplasty (FALK) with repeat FALK. METHODS: Clinical and histopathological study of 2 eyes of 2 patients with a recurrence of TGFBI dystrophy. Patient 1 had Reis-Buckler corneal dystrophy, and patient 2 had granular corneal dystrophy GCD type 1. RESULTS: Patient 1 had FALK 8 years ago, when she was 23 years old. Patient 2 had FALK 7 years ago at the age of 24 years. Slit-lamp examination showed recurrence in the subepithelial layer of the anterior lamellar graft as confluent chalky white granular deposits. Anterior segment optical coherence tomography highlighted the deposits in the subepithelial region of the anterior lamellar graft. The anterior lamellar graft with deposits was removed and replaced with another graft created using femtolaser dissection of a healthy donor. The parameters for femtosecond laser-assisted donor dissection was similar to the size and depth as the previously used donor. The best-corrected visual acuity was restored to 20/30 in patient 1 and 20/25 in patient 2. The histology of the anterior lamellar graft showed eosinophilic deposits between the epithelium and the Bowman layer in both samples. In addition, the corneal sample from patient 2 revealed Bowman layer breach at some places and few deposits at 1 edge of the lamellar graft. CONCLUSIONS: Repeat FALK with a healthy donor is effective in the management of recurrence of deposits. The histology of the recurrence in the anterior lamellar graft revealed eosinophilic deposits predominantly between the epithelium and Bowman layer.

Global Transcriptomic Profiling of Innate and Adaptive Immunity During Aspergillus flavus Endophthalmitis in a Murine Model.

Purpose: Fungal endophthalmitis is characterized by chronic inflammation leading to the partial or complete vision loss. Herein, we analyzed the transcriptomic landscape of Aspergillus flavus (A. flavus) endophthalmitis in C57BL/6 mice to understand the host-pathogen interactions. Methods: Endophthalmitis was induced by intravitreal injection of A. flavus spores in C57BL/6 mice and monitored for disease progression up to 72 hours. The enucleated eyeballs were subjected to histopathological analysis and mRNA sequencing using the Illumina Nextseq 2000. Pathway enrichment analysis was performed to further annotate the functions of differentially expressed genes (DEGs) and validation of cytokines was performed in vitreous of patients with fungal endophthalmitis using multiplex ELISA. Results: Transcriptomic landscape of A. flavus endophthalmitis revealed upregulated T-cell receptor signaling, PI3K-AKT, MAPK, NF-κB, JAK-STAT, and NOD like receptor signaling pathways. We observed significant increase in the T-cells during infection especially at 72 hours infection along with elevated expression levels of IL-6, IL-10, IL-12, IL-18, IL-19, IL-23, CCR3, and CCR7. Furthermore, host-immune response associated genes, such as T-cell interacting activating receptor, TNF receptor-associated factor 1, TLR1, TLR9, and bradykinin receptor beta 1, were enriched. Histopathological assessment validated the significant increase in inflammatory cells, especially T-cells at 72 hours post-infection along with increased disruption in the retinal architecture. Additionally, IL-6, IL-8, IL-17, TNF-α, and IL-1ß were also significantly elevated, whereas IL-10 was downregulated in vitreous of patients with Aspergillus endophthalmitis. Conclusions: Regulating T-cell influx could be a potential strategy to modulate the excessive inflammation in the retina and potentially aid in better vision recovery in fungal endophthalmitis.

Band-shaped keratopathy in HNF4A-related Fanconi syndrome: a case report and review of the literature.

BACKGROUND: Fanconi's syndrome (FS) is characterized by type-2 renal tubular acidosis, short stature, and renal rickets, along with glycosuria, aminoaciduria, hypophosphaturia, and urinary bicarbonate wasting. The genetic form of FS has been linked to HNF4A variants. Although additional clinical features such as hearing impairment have recently been associated with HNF4A-linked FS, its ocular manifestation has not been described. MATERIAL AND METHODS: Presenting a case of a 5-year-old male child with bilateral progressive corneal opacification and the presence of bilateral greyish-white deposits in the interpalpebral region since infancy. A next-generation sequencing (NGS)-based genetic testing was performed for the child followed by parental genetic testing for the identified variant. Furthermore, relevant works of literature were reviewed related to this condition. RESULTS: Detailed corneal findings showed a bilateral band-shaped keratopathy (BSK) in the patient. Physical and systemic findings showed signs consistent with FS. Sequencing analysis revealed a novel heterozygous c.635C>T, (p.Pro212Leu) variant in the HNF4A gene in the proband and mother, while the father had a normal genotype. CONCLUSIONS: Our case highlights the occurrence of BSK in an exceptionally rare manifestation of hereditary FS linked to HNF4A gene variant. The variant exists both in proband and asymptomatic mother. Therefore, the variable penetrance which is known to exist in HNF4A is acknowledged in this context. This report suggests the first documented instance establishing a plausible connection between BSK and HNF4A-associated FS, characterized by the variable penetrance attributed to the HNF4A gene.

Anterior segment optical coherence tomography and ultrasound biomicroscopy in the diagnosis of subconjunctival mycosis mimicking nodular scleritis.

A female patient in her 20s presented with a bulbar conjunctival mass lesion that was diagnosed as nodular scleritis. It was treated with topical and oral steroids in another hospital. Imaging was done using anterior segment optical coherence tomography and ultrasound biomicroscopy, which helped to rule out scleritis and subconjunctival cysticercosis. Histopathology of the excision biopsy specimen revealed fungal filaments. Topical antifungals were started, and the condition resolved without recurrence after therapy. Although rare, infections should be considered in the differential diagnosis of conjunctival mass lesions. Imaging can help to rule out other entities and guide towards appropriate management.

Oral mucous membrane grafting for unilateral lid margin keratinization following radiotherapy.

We describe the outcomes of oral mucous membrane grafting as a surgical technique for unilateral lid margin keratinization following radiotherapy. A 47-year- old woman presented with an 8-month history of a white spot in her right eye. She had a history of adenoid cystic carcinoma of the right spheno-ethmoid sinus, for which she underwent radiotherapy. Slit-lamp evaluation revealed lid margin keratinization of the right upper and lower eyelids and a keratin plaque on the corneal surface. We performed excision of the keratin plaque and lid margin keratinization, followed by oral mucous membrane grafting of the upper and lower eyelid margins. Histopathological evaluation of the excised lid margin revealed keratinized stratified squamous epithelium, consistent with lid margin keratinization. The corneal surface and lid margins showed no recurrent keratin deposition at the final follow-up, 11 months postoperatively.

Updates on congenital hereditary endothelial dystrophy.

Congenital hereditary endothelial dystrophy (CHED) is a rare genetic corneal disorder causing progressive cornea clouding and significant visual impairment. CHED remains a leading indication for pediatric corneal transplantation despite its infrequency, particularly in regions with high consanguinity rates like Southeast Asia. Identifying the Solute Carrier Family 4 Member 11 (SLC4A11) gene as the genetic basis of CHED has led to the discovery of it's various genetic variations. However, a comprehensive understanding of its clinical-genetic correlation, pathophysiology, and optimal management is ongoing. This review aims to consolidate current knowledge about CHED, covering its genetic origins, pathophysiological mechanisms, clinical presentation, and management strategies. Surgical intervention, such as penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK), remains the primary treatment. DSAEK and DMEK offer advantages over PK, including quicker visual recovery, reduced complications, and longer graft survival, especially in the pediatric age group. The timing of surgical interventions depends on disease severity, age at presentation, comorbidities, and visual potential. Elevated oxidative stress in CHED corneal tissue suggests potential benefits from anti-inflammatory drugs to rescue mutated endothelial cells. Considering the limitations of corneal graft surgeries, exploring novel gene-based molecular therapies are essential for future management. Early diagnosis, appropriate surgical interventions, amblyopia control, and genetic counseling for predictive analysis are pivotal for optimizing CHED management. A multidisciplinary approach involving ophthalmologists, researchers, and genetic counselors is essential for precise diagnosis and optimal care for CHED patients.

Experimental and probabilistic model validation of ultrasonic MEMS transceiver for blood glucose sensing.

In contrast to traditional laboratory glucose monitoring, recent developments have focused on blood glucose self-monitoring and providing patients with a self-monitoring device. This paper proposes a system based on ultrasound principles for quantifying glucose levels in blood by conducting an in-vitro experiment with goat blood before human blood. The ultrasonic transceiver is powered by a frequency generator that operates at 40 kHz and 1.6 V, and variations in glucose level affect the ultrasonic transceiver readings. The RVM probabilistic model is used to determine the variation in glucose levels in a blood sample. Blood glucose levels are measured simultaneously using a commercial glucose metre for confirmation. The experimental data values proposed are highly correlated with commercial glucose metre readings. The proposed ultrasonic MEMS-based blood glucometer measures a glucose level of [Formula: see text] mg/dl. In the near future, the miniature version of the experimental model may be useful to human society.

Objectively measuring anterior segment alterations in the eyes of mucopolysaccharidoses: Its utility in early diagnosis of glaucoma.

Purpose: Our study aimed to evaluate the utility of the anterior segment morphometry for objectively assessing anterior segment architectural changes of corneal clouding in the mucopolysaccharidoses (MPS) cohort and to investigate whether these measurements correlate with the slit-lamp findings on the cornea and early diagnosis of glaucoma. Methods: This retrospective study involved 70 eyes of 35 children with cloudy cornea due to MPS variants. Anterior segment architectural alterations were measured using anterior segment imaging and biometry in MPS children and compared with controls. Results: Mean age of the cohort at the time of assessment was 7.9 ± 4.5 years. Males constituted two-thirds of the cohort. Variants of MPS with cloudy cornea were as follows: Type I (62%), Type IV (11%), and Type VI (22%). Morphometric measurements were available in 22 eyes of 11 MPS children and an age-matched healthy control group. There were significant differences between MPS cohort and controls in refraction in Diopters (5.03 ± 0.39 and 0.01 ± 0.04; P < 0.0001), axial length (AXL) in mm (21.39 ± 0.28 and 23.04 ± 0.28; P = 0.0002), average keratometry in Diopters (40.67 ± 0.44 and 42.83 ± 0.44; P < 0.0001), anterior chamber depth (ACD) in mm (2.92 ± 0.07 and 3.65 ± 0.07; P < 0.0001), and intraocular pressure (IOP) in mmHg (25.2 ± 2.0 and 14.1 ± 2.3; P = 0.0003). Secondary glaucoma was observed in 28% of the MPS cohort. Conclusion: The anterior segment morphometry in the cloudy cornea due to MPS provides an objective measurement of anterior segment architectural changes, thus diagnosing early-onset secondary glaucoma. These findings highlight that cloudy cornea due to MPS variants merits close monitoring throughout life.

Clinical profile of keratitis treated within 3 months of acute COVID-19 illness at a tertiary care eye centre.

PURPOSE: To report the spectrum of keratitis treated within 3 months of acute COVID-19 infection. METHODS: Retrospective, descriptive case series study of 19 eyes of 16 patients who presented at tertiary eye care centre in Southern India. RESULTS: Median age of the patients was 43(IQR 35-55.5) years. Majority (15/16, 93.75%) were males. Unilateral affliction was predominant (13/16, 81.25% patients). Nine had a history of hospitalization, five had received oxygen supplementation and five had been treated with steroids during COVID-19 illness. The median duration between COVID-19 diagnosis and the ocular symptoms in the eye was 29 (IQR 22-57) days. Microbiological diagnosis consisted of microsporidia in nine eyes of seven patients, fungus in six patients, Pythium in one patient, and herpes zoster ophthalmicus in one patient. One patient had neurotrophic keratitis. Therapeutic penetrating keratoplasty was performed in five patients, glue application in two patients and three were managed with tarsorrhaphy with/without amniotic membrane grafting or tenonplasty. There was medical and surgical cure in all patients. CONCLUSIONS: Microsporidia was the commonest cause of keratitis, followed by fungal infection. Majority of the microsporidia infections were keratoconjunctivitis. The fungal isolates identified were Aspergillus and Mucor species. All patients responded to conventional management guidelines with favourable outcomes.

Amniotic Membrane Grafting for Ocular Surface Inflammation Following Topical Interferon Alpha 2b Therapy.

We describe a rare case of a 58-year-old female with ocular surface squamous neoplasia (OSSN) in her left eye. She was treated for 12 months with topical interferon alpha-2b (IFNα-2b) eye drops and OSSN resolved completely. She presented with a whitish elevated lesion involving the cornea, limbus, and conjunctival surface after discontinuation of topical IFNα-2b. Excision biopsy along with amniotic membrane grafting was done to stabilize the ocular surface. Histopathological evaluation of the excised tissue revealed ocular surface inflammation with no evidence of malignancy.

Structural, Morphological, Optical and Electrical Characterization of Gahnite Ferroan Nano Composite Derived from Fly Ash Silica and ZnO Mixture.

The synthesis of a high value-added product, gahnite ferroan nano composite, from a mixture of fly ash silica and ZnO is a low-cost and non-expensive technique. The XRD pattern clearly reveals the synthesized product from fly ash after leaching is a product of high-purity gahnite ferroan composite. The grains are mostly cubical in shape. The optical band gap of powdered gahnite ferroan nano composite is 3.37 eV, which acts as a UV protector. However, the bulk sample shows that the 500 to 700 nm wavelength of visible light is absorbed, and UV light is allowed to pass through. So, the bulk sample acts as a band pass filter of UV light which can be used in many optical applications for conducting UV-irradiation activity. Dielectric permittivity and dielectric loss increase with a rise in temperature. The increase in the ac conductivity at higher temperatures denotes the negative temperature coefficient resistance (NTCR) behavior of the material.

Ultrasound-guided supine mini-percutaneous nephrolithotomy in ectopic pelvic kidney.

Management of urolithiasis in an ectopic pelvic kidney is challenging and laparoscopic pyelolithotomy and laparoscopy-guided percutaneous nephrolithotomy (PCNL) are commonly favored options. We report a case of ultrasound-guided supine mini-PCNL in ectopic pelvic kidney in an adolescent female. Complete stone clearance was achieved with an uneventful postoperative period. Ultrasound-guided supine mini-PCNL is safe and effective treatment option for the management of calculus in the ectopic pelvic kidney. The risk of injury to surrounding structures associated with ultrasound modality of access can be avoided with proper case selection and careful technique.

Histopathological spectrum of ocular surface squamous neoplasia: A retrospective study of 776 lesions.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) comprises neoplasm arising from the ocular surface, which includes conjunctiva, cornea, and limbus and ranges from mild dysplasia to invasive squamous cell carcinoma. PURPOSE: The aim of this work was to study the spectrum of OSSN based on histopathological analysis. Materials and. METHODS: This was a retrospective cross-sectional study comprising 776 histopathologically diagnosed cases of OSSN from January 2004 to December 2014. RESULTS: The mean age of presentation of OSSN was 45 years (median, 45 years; 2 to 87 years) with male preponderance (74%). The most common age group of presentation was 41-60 years (n = 299; 39%). The most common type of OSSN was invasive squamous cell carcinoma seen in 50% (n = 383) eyes followed by severe dysplasia/carcinoma in situ in 31% (n = 250) eyes. Tumor infiltration at base was seen in 16% (n = 124), positive margins in 32% (n = 248), scleral infiltration in 14% (n = 109), intraocular extension in 3% (n = 23), and orbital extension in 4% (n = 26) eyes. OSSN was associated with actinic keratosis in 21% (n = 165) cases. CONCLUSION: Based on histopathology, invasive squamous cell carcinoma is the most common form of OSSN in the Asian Indian population.