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.

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.

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.

Lacrimal Gland Botulinum Toxin Injection Versus Simple Glandular Needling: Histopathological and Electron Microscopic Evidence and Potential Clinical Implications.

PURPOSE: To investigate the histopathological and ultrastructural changes in the lacrimal glands (LGs) of rabbits following either botulinum toxin (BTX) injection or simple glandular needling. METHODS: Twenty-four LGs of 24 eyes of 12 healthy New Zealand white rabbits were included in the study. Of these, 4 LGs of 4 eyes of 2 rabbits were used as controls. In the intervention group, all the right LG received 5 U in 0.1 ml of BTX-A (Botox, Allergan, Dublin, Ireland) and the left LG received simple glandular needling under general anesthesia. The BTX-A was injected directly into the LG via the transconjunctival route under direct visualization. For simple needling, 5 LG passes were made through a single-entry point using a 29-gauge needle mounted on an empty tuberculin syringe. The rabbits did not receive any postoperative medications other than lubricants. The rabbits were sacrificed at 8 weeks and the 20 treated and 4 control LG's were retrieved for histopathological and transmission electron microscopic (TEM) analysis as per standard protocols. RESULTS: In comparison to the control LG samples, both the treated groups showed pathological changes, which were more pronounced in the simple needling group. The BTX-A-treated LGs showed mild to moderate acinar atrophy, few degenerating acini and patchy chronic inflammatory infiltrates with thick hyalinized collagen within the glandular stroma. TEM analysis showed the cytosol of few acinar cells to contain vacuoles and autophagosomes with marginal chromatin condensation of the nucleus and an eccentric nucleolus. The LGs treated with simple needling showed marked pathological changes which include moderate to severe, focal, and diffuse acinar atrophy, dense stromal fibrosis, inflammatory infiltrates, and peri-vasculitis. TEM analysis showed focal disorganized acinar morphology, loss of intra-acinar and ductal architecture, and needle track zones with surrounding fibrotic areas. CONCLUSIONS: Histopathological and ultrastructural changes were noted in the LGs treated with BTX-A and simple glandular needling. Simple needling of the LG has the prospect to be an effective and cheaper alternative to BTX-A.

Poorly differentiated primary adenocarcinoma of the lacrimal sac and the nasolacrimal duct.

Primary adenocarcinoma of the lacrimal drainage system is a rare malignancy. Poorly differentiated subtypes of this tumor demonstrate aggressive behaviors, and metastasis is not uncommon. We present a patient with poorly differentiated adenocarcinoma of the lacrimal sac and nasolacrimal duct with an orbital extension. The case was managed by a combined external and endoscopic approach excision followed by adjuvant radiotherapy.

Inflammation, vascularization and goblet cell differences in LSCD: Validating animal models of corneal alkali burns.

Limbal stem cell deficiency (LSCD) is one of the serious cause of visual impairment and blindness with loss of corneal clarity and vascularization. Factors such as ocular burns (acids, lime, thermal), genetic disorders or infections results in the loss of limbal stem cells leading to LSCD. Reliable animal models of LSCD are useful for understanding the pathophysiology and developing novel therapeutic approaches. The purpose of the present study was to validate small and large animal models of LSCD by immunohistochemcal, clinical and histopathological comparison with human. The animal models of LSCD were created by topical administration of sodium hydroxide on the ocular surface of C57BL/6 mice (m, n = 12) and New Zealand white rabbits (r, n = 12) as per the standard existing protocol. Human corneal specimens (h, n = 12) were obtained from tissue bank who had chemical burn-induced LSCD. All samples were either paraffin embedded or frozen in cryogenic medium and the sections were processed for Hematoxylin-Eosin and Periodic Acid-Schiff staining to analyse the morphology and histopathological features of the corneal surface such as vascularization, inflammation, presence of goblet cells, epithelial hyperplasia and keratinization. Immunofluorescence was performed to distinguish between corneal (CK3+), conjunctival (CK19+) and epidermal (CK10+) epithelial phenotype. Histological analysis of corneal specimens from the three groups showed the presence of goblet cells (h:83%, m:50%, r:50%, p = 0.014), epithelial hypertrophy (h:92%, m:50%, r:66.6%, p = 0.04), epithelial hyperplasia (h:50%, m:17%, r:17%, p = 0.18), intra epithelial edema (h:42%, m:33%, r:100%, p = 0.02), stromal inflammation (h:100%, m:67%, r:67%, p = 0.01) and stromal vascularization (h:100%, m:50%, r:67%), in varying proportions. Immunostaining showed presence of total LSCD (CK19 + and/or CK10+, CK3-) in 92% of human and 50% of animal specimens. While partial LSCD (CK19 + and/or CK10+, CK3+) was seen in 8% of human and 50% of animal specimens. Our study shows the significant differences in the extent of vascularization, inflammation, epithelial thickness and goblet cell formation in mice and rabbit models of LSCD when compared to post-chemical burn LSCD in human corneas. In both mice and rabbit models complete LSCD developed in only 50% of cases and this important fact needs to be considered when working with animal models of LSCD.

Punctal and peri-punctal involvement in Urbach-Wiethe syndrome: case report and review of literature.

Urbach-Weithe syndrome is an exceedingly rare multisystem disorder characterized by pathognomonic clinical findings of multiple beaded papules along the eyelid margins and peri-ocular areas and hoarseness of voice secondary to intercellular deposition of periodic acid Schiff (PAS)-positive hyaline material. Lacrimal drainage anomalies are not well defined in this syndrome; however, punctal involvement and acquired nasolacrimal duct obstructions have been reported. We present a patient of Urbach-Weithe syndrome with bilateral punctal and peri-punctal involvement.

Dacryocystosclerotherapy as an alternative to dacryocystectomy.

Purpose: The aim of this study was to perform a histopathological assessment of the efficacy of sclerosing agents in dacryocystosclerotherapy (DCST) and to evaluate its role as an alternative to dacryocystectomy (DCT) in a specific group of patients. Methods: Thirteen lacrimal drainage systems of 10 patients with primary acquired nasolacrimal duct obstruction (PANDO) were studied. All patients were awaiting a DCT, indications being repeated attacks of dacryocystitis with severe systemic or ocular co-morbidities and/or refusal for a dacryocystorhinostomy. Fluorescent labelled sodium tetradecyl sulphate (SDS) or bleomycin were used as sclerosing agents for a DCST taking specific precautions. All patients underwent a DCT after 4 weeks and histopathological evaluation was performed to assess the changes and extent of DCST. Results: There were nine females and one male, and all patients were above the age of 60 years. Of the 13 lacrimal systems studied, the mean duration of PANDO was 1.3 years. All the patients had associated systemic and/or ocular co-morbidities. SDS and bleomycin were used in 6 and 7 lacrimal systems, respectively. The mean doses used for SDS and bleomycin were 0.26 and 0.31 cc, respectively. The post-injection phase was uneventful except for one patient who had a moderate inflammation, which resolved with low dose oral steroids. Histopathological features were more marked in the SDS group and included loss of epithelium, luminal closure, gross fibrosis across the lacrimal sac wall, congestion and hyalinization of blood vessels, and multiple areas of haemorrhages in the sac wall. Conclusions: DCST is a safe and effective alternative to DCT in very carefully selected patients. Histopathology demonstrates SDS to be more effective as compared to bleomycin.

Large peri-punctal eccrine hidrocystoma.

Eccrine hidrocystoma is a benign cystic tumor. Such benign cystic lesions may be a cosmetic concern, or when large, can cause eyelid malpositions. We report a patient with a peri-punctal hidrocystoma of the eyelid.

Clinical diversity in macular corneal dystrophy: an optical coherence tomography study.

PURPOSE: To characterise the corneal deposits of macular corneal dystrophy and correlate with high-resolution optical coherence tomography (OCT). METHODS: A total of 23 eyes of 15 patients were evaluated for clinical features on slit lamp biomicroscopy, and high-resolution OCT was performed to correlate the clinical findings. The deposits were characterised based upon their location and level in the corneal layers. RESULTS: Mean age was 31.5 (Range 20-67) years. The stromal deposits were restricted to central 8 mm in 9 eyes; in the rest of the 14 eyes, the deposits were seen in both central and peripheral cornea. In one patient, no such distinction could be made due to diffuse nature of the deposits throughout the cornea with sparing of 1-2 mm of the cornea internal to the limbus. The central deposits were in the anterior stromal layers, while the peripheral deposits were in the deep stromal corneal layers and non-contiguous with the anterior stromal deposits. In one patient aged 67 years, the peripheral deposits in deep corneal layers were more prominent than the central anterior stromal deposits and were associated with a significant thickening of Descemet membrane. CONCLUSIONS: MCD exhibits a clinically diverse presentation as revealed on the clinical and optical coherence tomography study. Immunophenotype and genotype-phenotype correlation may further help in understanding various clinical presentations of MCD.

Lacrimal Drainage System Involvement in Linear Scleroderma.

Linear scleroderma is a localized variety of scleroderma characterized by fibrotic areas of the dermis involving head region without systemic features. Ocular involvement has been sparsely reported in the form of episcleritis, dry eye, and uveitis. We describe a 42-year-old man with linear scleroderma, en coup de sabre type with associated nasolacrimal duct obstruction and prolonged dacryocystitis.

Ophthalmic Artery Occlusion Following Transconjunctival Orbitotomy.

Postoperative blindness after orbital surgery is an extremely rare and a disastrous complication. Ophthalmic artery occlusion as a cause of such unexpected vision loss has not been documented in literature. The authors report a case of a middle aged man who developed sudden vision loss due to ophthalmic artery occlusion following transconjunctival excision of orbital schwanomma. The possible mechanisms contributing to the loss of vision are discussed and preventive strategies are suggested to reduce the incidence of this complication.

Superperc: A new technique in minimally-invasive percutaneous nephrolithotomy.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) has undergone significant changes in recent years in the quest for improving efficacy and reducing morbidity. Newer minimally-invasive modalities of PCNL such as mini-PCNL, ultra-mini PCNL, and micro-PCNL have evolved with advancement in optics and technology. However, with these newer advancements, migration of small fragments produced with laser lithotripsy remains a concern, which may result in incomplete stone clearance. We describe a new technique of PCNL termed "Superperc", that utilizes suction to remove all the fragments and maintain one-way flow. METHODS: This was a prospective observational study involving 52 consecutive patients who underwent PCNL with the Superperc technique from April 2014 to June 2015. Surgery was performed using a pediatric ureteroscope used as a nephroscope and a specially designed sheath with a suction attachment. The Superperc uses a 10/12 F tract size, specially designed Superperc sheath (Shah Sheath) with suction mechanism and a pediatric ureteroscope (4.5/6 Fr, Richard Wolf) as nephroscope. RESULTS: The mean age of the group was 41.8 years (range 6-84) with 33 males and 19 females. Mean stone size was 19.11 mm (range 10-37 mm) and mean operative time was 40.9 min (range 26-92 min). Twenty-seven renal units had upper calyceal puncture, whereas 12 had middle, 8 lower calyceal and 5 had two punctures. DJ stent was placed in 20 patients, whereas 32 patients were totally tubeless. Only three patients required a nephrostomy tube. The mean hemoglobin drop was 0.32 g with no blood transfusion. Postoperatively, three patients had a mild fever and one had transient hematuria. The stone clearance rate in our study was 96.15% and the mean hospital stay was 31.5 h (range 22-76 h). CONCLUSION: Superperc is a new technique of minimally-invasive PCNL and can be successfully done with minimal modification in armamentarium, with the potential advantage of good stone clearance.

Histopathology and Immunophenotyping of Congenital Lacrimal (Anlage) Fistulae.

PURPOSE: To report the histopathological and immuno histochemical features of congenital lacrimal fistulae. METHODS: Retrospective chart review of all patients who underwent a fistulectomy for congenital lacrimal fistulae, over a 3-year period from a single surgeon's (M.J.A.) database, were included in the study. A detailed lacrimal system evaluation was performed, and intraoperative findings were documented. The excised fistulae were studied using hematoxylin and eosin and periodic acid-Schiff staining. Immunophenotyping was performed using CD3, CD5, CD10, and CD20. RESULTS: Twelve excised fistulae of 12 patients were studied. The mean age at presentations was 5.3 years (range, 3-11 years). The deeper parts of the fistulae were lined with hypertrophied stratified squamous epithelium similar to canalicular tissue in 83.3% (10/12), reflecting its origin from the canalicular tissue, and 16.7% (2/12) originated from the lacrimal sac and were lined with columnar epithelium with areas of squamous metaplasia. The subepithelial areas showed presence of fibrosis and chronic inflammatory infiltrate. The infiltrates were lymphoplasmacytic and were positive for CD3, CD5, and CD20 and negative for CD10 immunostaining. CONCLUSION: Hypertrophied stratified squamous lining was the commonest finding. Immunophenotyping revealed features of chronic inflammatory infiltrate composed of a mixture of both T and B lymphocytes. Histopathological analysis of fistulae may be of adjunctive value in determining the origin of the anlage.

Histopathology, Immunohistochemistry, and Electron Microscopic features of a Dacryocystorhinostomy Ostium Cicatrix.

PURPOSE: The aim of this study is to report the histopathological, Immunohistochemical, and ultrastructural features of a dacryocystorhinostomy ostium cicatrix. METHODS: A prospective histopathological study was performed in a tertiary eye care setting. Scarred nasal mucosal tissues obtained during endoscopic revisions of 10 previously failed dacryocystorhinostomies secondary to complete cicatricial closure of the ostia were studied. The tissue specimens were analyzed using hematoxylin and eosin, periodic acid-Schiff staining. Special stains used include Masson's trichrome and Alizarin red. Immunohistochemistry was performed using vimentin, smooth muscle actin, CD3, CD5, and CD20. Specimens were processed for ultrastructural analysis as per standard protocols for transmission electron microscopy. RESULTS: The respiratory epithelial regeneration was noted to be complete. Irregular laying of deeply eosinophilic and hyalinized collagen with intervening fibroblasts was noted. Focal areas of new bone formation were seen within the cicatricial tissue with osteocytes and ongoing osteoblastic rimming. The infiltrates were mixture of both T and B lymphocytes and were positive for CD3, CD5, and CD20 immunostaining. Electron microscopy showed disorganized collagen fibrils with numerous fibroblasts and mononuclear inflammatory infiltrate. Amorphous bony osteoid within a fibrillar background with metabolically active osteoblasts showed a vesicular cytoplasm, hyperplastic proliferating mitochondria, large Golgi apparatus, and dense endoplasmic reticulum. CONCLUSION: There is new bone formation within the dense connective tissues of a dacryocystorhinostomy cicatrix. This study may provide useful inputs for further basic science studies aimed at better understanding of wound healing in failed dacryocystorhinostomy.

Punctal stenosis: histopathology, immunology, and electron microscopic features-a step toward unraveling the mysterious etiopathogenesis.

PURPOSE: To study the histologic, immunohistochemical, and electron microscopic features of puncta and proximal vertical canaliculi to understand the etiopathogenesis of punctal stenosis. METHODS: Prospective study of 26 stenosed punctae that were collected following a punctoplasty. Sixteen were from lower eyelid and 10 from upper eyelid. Histopathological examination was performed on 20 punctae using hematoxylin-eosin, periodic acid-Schiff, and Masson trichrome staining. Immunohistochemical patterns were analyzed after staining with leukocyte common antigen or CD45, CD3, CD5, CD10, CD20, CD138, and smooth muscle actin. Six punctae (3 upper, 3 lower) were separately processed for electron microscopic studies as per standard protocols. RESULTS: All punctae showed evidence of subepithelial and subconjunctival fibrosis. Thirty percent (6/20) showed extensive fibrosis. Inflammation was noted in 80% (16/20) of the samples; however, 20% (4/20) showed severe inflammation. Strong immunoreactivity was noted, with CD45 and CD3 in 80% (16/20) with predominance in the subepithelial areas. Focal immunoreactivity was noted for CD10, CD20, and CD138. Immunoreactivity was negative for CD5. Electron microscopic features include blunted epithelial microvilli, numerous fibroblasts, extensive and irregularly arranged collagen bundles, mononuclear infiltration in the vicinity of fibroblasts or in between collagen bundles, and inter- and intracellular edema in areas of inflammation. CONCLUSIONS: Chronic inflammation and subsequent fibrosis appear to be the basic ultrastructural response to various noxious stimuli. Mononuclear inflammatory infiltration in the vicinity of fibroblasts could possibly reflect a close cellular interaction between these 2 cells.

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.