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.

Influence of Webinar-Based Learning on Practice of Percutaneous Nephrolithotomy: Outcomes of a Global Survey.

Background: With webinars looking to be the mainstay post-pandemic, it is important to demonstrate whether webinars are, indeed, effective educational tools for professional training and skill acquisition. We aim at demonstrating, via a global survey, the efficacy of webinars on percutaneous nephrolithotomy (PCNL) and how this knowledge transforms clinical practice. Methods: A structured online survey covering the following sections: (1) Demographics, (2) PCNL techniques, and (3) PCNL equipment was circulated. The target study population were practicing urologists and residents. Categorical data were presented with counts and percentages, and they were compared by using Chi-square test. Continuous data were analyzed with non-parametric methods. Respondents were dichotomized according to attendance of webinar type, attendees of dedicated PCNL webinars (Group A), or attendees of endourological webinars that discussed some aspects of PCNL (Group B). Results: A total of 303 respondents from 38 countries participated. Overall, 91.7% (n = 278) were in Group A and 8.3% (n = 25) were in Group B; 77.9% were younger than 50 years, whereas 51.8% had more than 10 years of urology experience. In group A, urologists of all ages, in academic institutions and private practitioners, significantly benefited in gaining knowledge about the merits of newer devices and the role of suction-assisted devices in modern PCNL. The majority of group A also reflected that by attending a dedicated PCNL-based webinar they benefited in learning newer positions for PCNL access, especially supine, and how to effectively use laser as energy devices for lithotripsy. In Group B, the only area of benefit was in lasing techniques and the use of newer lasers such as the thulium fibre laser. Conclusion: Our survey positively validates the two proposed hypothesis, that is, webinars as a medium of education do benefit practicing urologists in knowledge and the clinical practice domains. Age, experience, or place of practice is no barrier to adopting newer mediums of education such as webinars.

Herpes Simplex Virus Anterior Uveitis in a Child Presenting as a Hypopyon in a White Eye.

PURPOSE: To report a rare ocular presentation of unilateral anterior uveitis with hypopyon in a 5-year-old child, suspected as masquerade. METHODS: Retrospective report. RESULTS: A 5-year-old boy presented with hypopyon-uveitis. Detailed systemic work-up was negative for masquerade and uveitis entities. He was started on oral and topical steroids but had reactivation on taper. Real-time polymerase chain reaction (PCR) test of aqueous fluid was positive for herpes simplex virus (HSV)-1 DNA. The inflammation resolved completely on oral acyclovir and topical corticosteroids. He subsequently underwent pars plana lensectomy, primary posterior capsulotomy and vitrectomy for complicated cataract. Post-operatively, vision improved to 20/400 with aphakic correction. Maintenance oral acyclovir was stopped after 3 months with no reactivation and amblyopia therapy was continued. CONCLUSION: This is a rare presentation of hypopyon uveitis due to HSV-1 in a child. The role of real-time PCR in establishing the diagnosis is crucial in such cases of diagnostic dilemma.

Clinical clues to the early diagnosis and management of ocular surface neoplasia following keratoplasty in xeroderma pigmentosa.

The purpose of this report is to highlight the early clinical signs and management of ocular surface neoplasia following penetrating keratoplasty in xeroderma pigmentosa. A 14-year-old girl reported increased conjunctival hyperemia, tearing, photophobia in the right eye at 6 months after penetrating keratoplasty that worsened rapidly over the subsequent 2 weeks. Slit lamp examination showed increased vascularity, epithelial haze and raised whitish lesions at the graft-host junction. Alcohol keratoepithelectomy was performed for confirming the diagnosis. Histology of the sample revealed severe dysplasia. The lesion resolved after surface plaque brachytherapy. The graft clarity was restored and maintained until the last follow-up of 15 months following brachytherapy. Exacerbated symptoms and clinical signs of increased vascularisation and epithelial lesions should arouse the suspicion of ocular surface neoplasia in grafted eyes. Early diagnosis and management can salvage the graft clarity.

High-Resolution Optical Coherence Tomography Angiography Characteristics of Limbal Stem Cell Deficiency.

This study aimed to identify the anterior segment high-resolution optical coherence tomography (HR-OCT) and HR-OCT angiography (HR-OCTA) features suggestive of limbal stem cell deficiency (LSCD) as confirmed by both impression cytology (IC) and in vivo confocal microscopy (IVCM). This was a single-centre prospective cross-sectional study including 24 eyes of 22 patients with clinical suspicion of LSCD based on peripheral superficial corneal vascularisation and scarring. On IC and IVCM, performed and interpreted by blinded observers, 12 eyes each were diagnosed with and without LSCD. Additionally, 10 eyes of 5 healthy volunteers with no ocular pathology were also imaged. The 136 HR-OCT/A images of these 34 eyes were analysed with respect to 12 imaging parameters; the parameters most suggestive of LSCD were identified and the sensitivity and specificity were calculated. In the LSCD group, the most common aetiology was ocular chemical burns (83%), whereas in the non-LSCD group, the most common aetiology was viral keratitis (67%). Multiple logistic regression analysis revealed that mean epithelial reflectivity, mean stromal reflectivity, and mean superficial vascular density were the parameters that were diagnostic of LSCD on HR-OCT/A (p < 0.0001). A ratio of the mean epithelial reflectivity to stromal reflectivity of >1.29 corresponded with a high sensitivity (91.7%) and specificity (98.75%); while a mean superficial vascular density score of >0.38 corresponded with a sensitivity of 97.9% and specificity of 73.8%. In conclusion, HR-OCT/A as a non-invasive imaging modality could prove to be a useful tool for confirming the diagnosis of LSCD, with potential clinical and research applications.

Peters Anomaly in Nail-Patella Syndrome: A Case Report and Clinico-Genetic Correlation.

PURPOSE: The purpose of this study was to report the clinicopathological features of Peters anomaly in a child with nail-patella syndrome. METHODS: Nail-patella syndrome (NPS) is a rare autosomal dominant connective tissue disorder characterized by several anomalies of the extremities, joints and nails, glomerulopathy, and rarely ocular involvement. NPS is caused by heterozygous loss-of-functional mutations in the LMX1B gene that encodes the LIM homeodomain proteins. RESULTS: This case reports a new association of Peters anomaly in a child with NPS that also had classic skeletal/nail anomalies and protein losing nephropathy. Furthermore, DNA sequence analysis identified a novel missense heterozygous mutation in the LMX1B gene (Transcript ID: NM_001174146) resulting in the replacement of tryptophan by serine in codon 266, suggesting that the mutation (p.Trp.266Ser) affects LMX1B function by disturbing its interactions with other proteins. To the best of our knowledge, this association of Peters anomaly is novel and has not been reported earlier in the ophthalmic and systemic literature on NPS. CONCLUSION: The corneal findings in our case with NPS are similar to those seen in congenital corneal opacification because of Peters anomaly. This novel association of Peters anomaly with NPS may be related to the effects of the LMX1B mutation on corneal development.

Lacrimal Fossa Bony Changes in Chronic Primary Acquired Nasolacrimal Duct Obstruction and Acute Dacryocystitis.

PURPOSE: This study aims to assess the bony lacrimal fossa changes in chronic cases of primary acquired nasolacrimal duct obstruction versus acute dacryocystitis. METHODS: A prospective study was performed on 25 bony lacrimal fossae of 25 eyes of 15 patients who underwent endoscopic dacryocystorhinostomy at a tertiary care Dacryology service over a period of 6 months. Ten patients with chronic PANDO (> 1 year) with bilateral involvement and five patients of unilateral acute dacryocystitis were recruited in the study. None of the patients had a history of trauma or previous surgeries or nasal disease in the past. The bone samples from the frontal process of the maxilla and the lacrimal bone were obtained during the osteotomy and subjected to routine histopathological examination. Special stains used were von Kossa, Masson trichrome, periodic acid Schiff, and Alcian blue. Immunohistochemistry was performed using CD68 antibodies. Patient demographics, clinical presentation, duration of the disease, and bony changes were analyzed in different patient subsets. RESULTS: The mean disease duration in the chronic PANDO subset was 3.1 years, whereas acute dacryocystitis was 6.8 days. There was no correlation between the bony changes and the laterality in the chronic subset. Periosteal thickness and fibrosis were universal in the chronic group but not in the acute dacryocystitis. There were also differences in the number of osteocytes per sq mm, osteoblast, osteoclast, bony remodeling, bony canals structure, and intrastromal fibrosis between the subsets. These changes within the chronic group increased with the duration of the disease. Interestingly, there was no evidence of any bony inflammation across the subsets in all the samples studied. CONCLUSION: Characteristic bony changes can be demonstrated in patients with chronic PANDO but not in acute dacryocystitis. The lack of bony inflammatory infiltrates may provide clues in understanding the peri-sac disease pathogenesis in acute dacryocystitis.