Lacrimal Sac Characteristics in Patients With Punctal and Canalicular Agenesis: Punctum Update (PUP) Study-Paper 3.

PURPOSE: To explore the endoscopic and histopathologic characteristics of the lacrimal sac (LS) and the nasolacrimal duct in cases with punctal agenesis presenting with LS swellings. METHODS: This is a prospective, interventional study of 13 LSs of 8 patients presenting with punctal agenesis and LS swellings over a 5-year study period (June 2018-July 2023). Complete ophthalmic examination was performed along with CT scans of the orbits. The LS was exposed with an anterior lacrimal crest incision and explored. The exterior and interior of the sac swelling were examined and LS flaps were sent for histopathological analysis. RESULTS: The mean age of the patients was 23 years with a male:female ratio of 5:3. All patients presented with swelling in the LS region. Occasional epiphora was the presenting feature in 6 patients. All patients had both upper and lower punctal agenesis on the affected side with associated LS swelling. CT scans showed a hypodense cystic swelling with expansion of the LS fossa and bony nasolacrimal duct ending abruptly short of the inferior meatus. Intraoperatively, the LS had thin, translucent walls with mucoid secretion and an absence of common canalicular opening. Histopathological analysis showed epithelium consistent with LS with less robust development of the sac walls and poorly structured lacrimal drainage-associated lymphoid tissue with scanty stromal inflammation. CONCLUSIONS: The development of LS and the nasolacrimal duct is structurally affected in patients with punctal agenesis. Retrograde approaches for epiphora resolution are not logical in such cases but conjunctivodacryocystorhinostomy with Jones tube can be a feasible option.

Caruncle and plica hypertrophy causing mechanical secondary acquired lacrimal duct obstruction: - SALDO update study (SUP) - paper I.

PURPOSE: To exclusively report the clinical category of mechanical secondary acquired lacrimal duct obstruction (SALDO) secondary to the caruncle and plica hypertrophy. METHODS: Prospective interventional case series involving 10 consecutive eyes with megalocaruncle and plica hypertrophy were enrolled in the study. All patients presented with epiphora secondary to a demonstratable mechanical obstruction of the puncta. All patients underwent high magnification slit-lamp photography and Fourier-domain ocular coherence tomography scans (FD-OCT) of the tear meniscus height (TMH) pre- and post-operatively at 1-month and 3-months. Caruncle and plica size, position, and their relationship to the puncta were noted. All patients underwent partial carunculectomy. Primary outcome measures were demonstrable resolution of the mechanical obstruction of the puncta and the reduction in the tear meniscus height. The secondary outcome measure was the subjective improvement of the epiphora. RESULTS: The mean age of the patients was 67 years (range: 63-72 years). The average TMH was 843.1 (range: 345-2049) microns pre-operatively and 195.1(91-379) microns at 1-month follow-up. All patients reported significant subjective improvement in epiphora at 6-months follow-up. One patient had bilateral granuloma at the surgical site at two weeks and was managed by simple excision and topical tapering steroids. Histopathology revealed hyperplastic epithelium with goblet cells with chronic inflammatory cells in the sub-epithelial region and the stroma. CONCLUSION: The role of the caruncle in the causation of mechanical SALDO needs to be carefully assessed in patients beyond the sixth decade. Excellent objective and subjective outcomes can be achieved by a partial carunculectomy and plica semilunaris excision.

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.

Proteomic profiling of exosomes in a mouse model of Candida albicans endophthalmitis.

Exosomes play pivotal roles in intercellular communication, and pathophysiological functions. In this study, we aimed to understand the role of exosomal proteome derived from C. albicans infected mice (C57BL/6) eyeball. Exosomes were characterized by Dynamic Light Scattering and Western blot, quantified and subjected to LC-MS/MS and cytokine quantification by ELISA. The average size of exosomes was 170-200 nm with number of exosomes amounted to 1.42 × 1010 in infected set compared to control (1.24 × 109). Western blot was positive for CD9, CD63 and CD81 confirming the presence of exosomes. IL-6, IL1ß, TNF-α, and IFN-γ levels were significantly elevated in infected eye at 72 h.p.i. Proteomic analysis identified 42 differentially expressed proteins, of these 37 were upregulated and 5 were downregulated. Gene Ontology (GO) revealed enrichment of cell adhesion, cytoskeleton organisation, and cellular response proteins such as aquaporin-5, gasdermin-A, CD5 antigen-like, Catenin, V-ATPase, and vesicle associated protein. Additionally, KEGG pathway analysis indicated the association of metabolic and carbon signalling pathways with exosomes from C. albicans infected eye. The protein cargo in exosomes released during endophthalmitis with C. albicans seems to play a unique role in the pathogenesis of the disease and further validations with larger cohort of patients is required to confirm them as biomarkers.

Atypical presentation of punctal keratin cyst: an underdiagnosed entity.

Punctal keratin cyst (PKC) is a rare disorder believed to be due to ectasia of the vertical canaliculus. The etiopathogenesis of this disorder is very poorly understood due to the paucity of literature. To the best of authors' knowledge, only two cases of punctal keratin cyst have been described earlier, which presented as cystic lesions. The authors report four cases of punctal keratin cyst which differ in clinical presentation and also describe the anterior segment ocular tomography features, which aids in recognition and diagnosis of this rare disorder. The key message of the article is that lack of a defined cyst on clinical examination and optical coherence tomography (OCT) cannot rule out the presence of a PKC. A combination of clinical, radiology, and histopathology are confirmative of the diagnosis. Once diagnosed, the subsequent outcomes with membranotomy and keratin curettage are excellent.

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.

Methicillin resistance in Staphylococcus aureus modulates the transcriptome and disease pathology in a murine model of endophthalmitis.

The ever-increasing incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) endophthalmitis is of particular concern as they are associated with poor outcomes. To compare the histology and whole transcriptome of Methicillin resistant (MRSA) and Methicillin-susceptible (MSSA) Staphylococcus aureus endophthalmitis in an experimental murine model. MRSA and MSSA endophthalmitis was induced in C57BL/6 mice and disease progression was scored clinically and histologically at 24 h p.i. Retinal changes were monitored by H&E, CD45, MPO and GFAP staining followed by retinal cell death evaluation. Whole Transcriptome was analysed using the SuperPrint G3 Mouse Gene Expression v2 chip. Differential gene expression analysis (Limma package, R) was done followed by enrichment of pathways (KEGG database). Increased corneal haze, diminished vitreous clarity and red reflex was observed in MRSA infected mice eye compared to MSSA (p = 0.04). Histological assessment also corroborated with increased disease severity in MRSA (p = 0.02). Although MRSA infected eye displayed higher CD45+ cells and greater GFAP intensity, the difference was not statistically significant. However, higher retinal cell death was found to be associated with the MRSA infection (p = 0.007). Our study also revealed that MRSA infection induces changes in host transcriptome (FC = 1.5, p = 0.05), revealing the involvement of several interleukins (IL-11,15,10,1ra), chemokines (CCL-11, CXCL-1), Interferon receptors, GM-CSF, M-CSF, MMPs, Neruopilin2 (NRP-2), Ubiquitin associated peptidase and apoptotic ligands. ErbB signalling, JAK-STAT, adipocytokine and Ras signalling were the top divergently enriched pathways. Our study confirms the differential host immune response triggered by MRSA infection in the eye. Our study may help to elucidate the mechanisms of pathogenesis and to identify additional candidate drug targets for the treatment of MRSA endophthalmitis.

Proteomic profiling of aspergillus flavus endophthalmitis derived extracellular vesicles in an in-vivo murine model.

Extracellular Vesicles (EVs) play pivotal roles in cell-to-cell communication, and are involved in potential pathological and physiological cellular processes. The aim of this study was to understand the proteomic cargo of these vesicles, in a murine model of Aspergillus flavus (AF) endophthalmitis. EVs were isolated from A. flavus infected C57BL/6 mice eyes by differential ultracentrifugation at 24 h post infection (p.i) and isolated EVs were characterized by Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Exocet assay, and western blot. Proteomic profiling of EVs was then evaluated by mass spectrometry (LC-MS/MS) and compared it with control uninfected mice. The average size of the EVs were 180-280 nm by DLS and the number of EVs increased to 1.55 × 1010 in infected mice in comparison to EVs from uninfected eye (1.24 × 109). Western blot was positive for CD9, CD63, and CD81 confirming the presence of EVs. LC-MS/MS analysis, identified 81 differentially expressed proteins, of these 22 were up-regulated and 59 were down-regulated. Gene Ontology (GO) analysis revealed enrichment of lipid metabolism, protein complex binding, and transferase activity, and the proteins associated were Aquaporin-5, CD177 antigen, Solute carrier family-25, and Calcium/calmodulin-dependent protein kinase. Additionally, KEGG pathway analysis indicated that glucagon signalling, metabolic, and PPAR signalling pathway were significantly associated with EVs from A. flavus infected mice eyes. The protein cargo in EVs from A. flavus endophthalmitis provides new insights into the pathogenesis of fungal endophthalmitis and validation of these proteins can serve as diagnostic and/or prognostic biomarkers for patients with a clinical suspicion of fungal endophthalmitis. LAY SUMMARY: EVs play an important role in cell communication. In our study proteomic profiling of EVs isolated from A. flavus infected mice provided new insights into the understanding of the pathobiology of A. flavus endophthalmitis and validation of these proteins can serve as biomarkers.

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.

Retinoblastoma associated with orbital pseudocellulitis and high-risk retinoblastoma: a study of 32 eyes.

PURPOSE: To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. METHODS: Retrospective study of 32 patients who underwent primary enucleation for RB presenting with orbital pseudocellulitis. RESULTS: All RB patients presented with orbital pseudocellulitis. The mean age at presentation of RB was 30 months (median, 24 months; range, 3-70 months). There were 14 (44%) males and 18 (56%) females. All patients were referred with a diagnosis of RB with orbital pseudocellulitis. Tumor was bilateral in 12 (38%) patients but orbital pseudocellulitis was unilateral in all cases. The pseudocellulitis features included proptosis (n = 9; 28%), eyelid edema (n = 22; 69%), conjunctival congestion (n = 23; 72%), and conjunctival chemosis (n = 15; 47%). Based on clinical features and orbital imaging, all patients were diagnosed to have group E intraocular RB. All patients received intravenous steroids prior to enucleation. On histopathology, tumor necrosis was present in all cases with a mean % necrosis of 60% (median, 60%; range, 10% to 90%). Most tumors (72%) were poorly differentiated. High-risk histopathology features were noted in 23 (72%) cases and adjuvant chemotherapy was advised for all these patients. The most common high-risk histopathology features included post-laminar optic nerve infiltration (34%) and scleral infiltration (22%). Over a mean follow-up period of 34 months (median, 9 months; range, < 1-188 months), there was no event of metastasis or death in any patient. CONCLUSION: RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.

Ocular surface squamous neoplasia in India: a study of 438 patients.

PURPOSE: To describe the clinical features, histopathology, treatment, and outcomes of patients with ocular surface squamous neoplasia (OSSN) presenting to a referral centre in India. METHODS: Retrospective interventional study. RESULTS: Of 438 patients, the mean age at presentation was 49 years. Human immunodeficiency virus infection was noted in 72 (16%), xeroderma pigmentosum in 22 (5%), hepatitis B virus infection in 14 (3%), and systemic cancer in 8 (2%) patients. Tumor pigmentation was noted in 243 (54%) tumors with a mean percentage of tumor pigmentation of 44% (median, 40%; range, 1 to 100%). Intraocular tumor extension was noted in 12 (3%), and orbital tumor extension in 16 (4%) eyes. Of the 381 treated lesions, excisional biopsy (n = 247; 65%) was the most common treatment modality. Of the 311 lesions with histopathology diagnosis of OSSN, invasive squamous cell carcinoma (n = 92; 30%) was the most common. Over a mean follow-up period of 11 months (median, 5 months; range, 1 to 108 months) in 368 patients, tumor recurrence was noted in 16 (4%) eyes, globe salvage was achieved in 341 (90%) eyes, vision salvage in 338 (89%) eyes, regional lymph node metastasis occurred in 9 (2%), and metastasis-related death in 9 (2%) patients. CONCLUSION: Pigmented OSSN is common in Asian Indian population. Appropriate management of OSSN is associated with good vision, globe, and life salvage rates in India.

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.

Malignant Phyllodes Tumor of the Breast With Metastasis to the Orbit: A Rare Case Report.

Phyllodes tumors are rare and account for 0.5% of all mammary neoplasms. They commonly present as lobulated breast tumors and have a variable clinical course. Histologically, phyllodes tumor is composed of 2 major elements: stromal element composed of spindle cells admixed with collagen and epithelial element in the form of epithelium lined cysts and clefts. Metastasis is rarely seen with phyllodes tumors. Sarcomatous component of phyllodes tumor metastasizes to lung, liver, adrenal, brain, and bones by hematogenous route. A thorough literature search did not reveal any report of orbital metastasis from malignant phyllodes tumor. Here, the authors describe a rare case of malignant phyllodes tumor of the breast with metastasis to the orbit in a 46-year-old female patient.

Anterior segment optical coherence tomography features of pseudoepitheliomatous hyperplasia of the ocular surface: a study of 9 lesions.

PURPOSE: To describe anterior segment optical coherence tomography (AS-OCT) features of pseudoepitheliomatous hyperplasia (PEH) of the ocular surface. METHODS: This is a retrospective study of 9 lesions of 8 patients with histopathologically proven PEH RESULTS: Mean age at diagnosis of PEH was 31 years (median 31 years; range 12 to 62 years). The lesion was unilateral in 7 (88%) patients and bilateral in one (12%). Two patients (25%) had xeroderma pigmentosum, who also had a history of prior surgical intervention in the same eye for conjunctival tumor excision. Referral diagnosis was ocular surface squamous neoplasia (OSSN) in all cases. Ocular surface mass (n = 4, 44%) was the most common presenting complaint. The mean duration of symptoms was 18 months (median 3 months; range < 1 to 84 months). All lesions were perilimbal, and the mean basal diameter of the tumor was 7 mm (median 6 mm; range 4 to 12 mm). Clinical diagnosis included OSSN (n = 5; 56%), PEH (n = 3; 33%), or leiomyosarcoma (n = 1; 11%). AS-OCT features included irregular hyperreflective epithelium, epithelial dipping, and subepithelial hyperreflective lesion with posterior shadowing in all cases. Histopathology confirmed the diagnosis of PEH in all cases. The underlying cause of PEH in these cases included vernal keratoconjunctivitis (n = 4; 44%), idiopathic severe blepharitis (n = 2; 22%), or prior surgical intervention (n = 2; 22%). No apparent cause could be determined in one eye (11%). CONCLUSION: Ocular surface PEH is a close mimicker of OSSN. Careful history-taking, clinical examination, and characteristic AS-OCT features aid in accurate diagnosis.

Spectrum of AS-OCT features of ocular surface tumors and correlation of clinico-tomographic features with histopathology: a study of 70 lesions.

PURPOSE: To assess the correlation between clinical and anterior segment optical coherence tomographic (AS-OCT) details and histopathological changes in various ocular surface lesions. METHODS: Prospective case series of 70 lesions in 65 patients. RESULTS: AS-OCT revealed epithelial changes in OSSN (n = 19; 44%), squamous papilloma (n = 3; 60%), nevus (n = 1; 33%), epithelial hyperplasia (n = 1; 33%), granular dystrophy (n = 1; 100%) and granulation tissue (n = 1; 100%); subepithelial changes in chronic inflammation (n = 4, 100%), lymphoma (n = 3; 100%) and arteriovenous malformation (n = 1; 100%); combined epithelial and subepithelial changes in OSSN (n = 24; 56%), squamous papilloma (n = 2; 40%), PEH (n = 3; 100%), nevus (n = 2; 67%), epithelial hyperplasia (n = 2; 67%), solar elastosis (n = 1; 100%), lobular capillary hemangioma (n = 1; 100%) and sebaceous carcinoma (n = 1; 100%). Epithelial involvement on AS-OCT paralleled the histopathological findings in 98% (n = 69) and subepithelial involvement in 83% (n = 58). The correlation of clinico-tomographic diagnosis with histopathology diagnosis was seen in 77% (n = 54) lesions. Sensitivity and specificity of AS-OCT as a diagnostic tool for detection of epithelial involvement were 100% and 92% and for subepithelial involvement was 98% and 100%, respectively. CONCLUSION: The correlation between AS-OCT and histopathology features determining epithelial and subepithelial involvement is excellent. It is a useful adjunctive tool for the diagnosis of ocular surface lesions.

Comparative evaluation of clinical characteristics of biopsy-proven conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma using image processing software programs.

PURPOSE: To identify morphological parameters aiding clinical differentiation of conjunctival intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (iSCC) and to demonstrate the utility of image processing software to objectively assess ocular surface squamous neoplasia (OSSN). METHODS: This retrospective case series included all biopsy-proven cases of OSSN presenting as an ocular surface nodule. Based on histopathology, lesions were classified as CIN and iSCC. Clinical image analysis utilized 'Contour' and 'ImageJ' software. The effect of predictors demography, seropositivity, lesion dimensions, keratin, pigmentation, corneal involvement, vascularity and feeder vessels on the final histopathologic grade were assessed. RESULTS: A total of 108 OSSN lesions (74 CIN and 33 iSCC) were included. Mean age was 46.1 ± 17.2 years in CIN and 47.2 ± 13.9 years in iSCC. By univariate logistic regression analysis, significant predictors of iSCC were HIV seropositivity (p < 0.0001), maximum diameter (p = 0.003), perpendicular to maximum diameter (p = 0.003), height (p = 0.003), nodular morphology (p = 0.006) and feeder vessels (p = 0.03), whereas gelatinous morphology (p = 0.02) was predictor of CIN. By multiple logistic regression, seropositivity was the predictor of iSCC (p < 0.0001, OR 13.33 ± 8.35, 95% CI 3.90-45.53). CONCLUSION: HIV seropositivity is an important predictor of iSCC. Large, thick, nodular lesions with feeder vessels may favor the diagnosis of iSCC, whereas gelatinous, small, flatter lesions without feeder vessels may favor CIN. In a first of its kind study, simple and objective analysis of OSSN with image processing software was demonstrated.

Overexpression of metastasis-associated in colon cancer 1 in retinoblastoma.

INTRODUCTION: Metastasis-associated in colon cancer 1 (MACC1), one of the prognostic markers for colonic and other tumours was noted to be overexpressed in retinoblastoma (Rb) Y79 cancer stem cells. This prompted us to evaluate its expression in primary Rb tumour and serum samples with clinicopathologic correlation. The interacting partner, c-MET was also evaluated in primary tumour tissues to explore the activation of MACC1 signaling. METHODOLOGY: This study was done following institutional review board approval from participating institutes. Semiquantitative gene expression for MACC1 was evaluated using formalin-fixed paraffin-embedded sections and unfixed tumour samples from primary Rb cases (n = 44). Immunolocalization for MACC1 was assessed in primary Rb tumours (n = 22), bone marrow aspirates with metastasis (n = 3), and c-MET expression was also assessed in Rb tumours (n = 17). Serum MACC1 levels were analysed using enzyme-linked immunosorbent assay in samples collected from Rb patients undergoing enucleation (n = 31), Rb patients with proven clinical metastasis (n = 3), and compared to appropriate controls. Clinicopathologic correlation of MACC1 expression was analysed using the medical records with specific reference to histologic risk factors (HRF) for metastasis and differentiation. RESULTS: High expression of MACC1 gene was noted in all the tumour samples (n = 44), more so in cases with versus without HRF (p < 0.0001). In cases with HRF, MACC1 and c-MET showed diffuse nuclear and cytoplasmic staining whereas it was predominantly cytoplasmic in cases without HRF. Mean immunoreactivity score of MACC1 and c-MET tissue immunolocalization revealed that cases with HRF showed significantly higher expression compared to cases without HRF (p < 0.05). Unlike the findings in colonic tumours, serum levels of MACC1 were lower in patients compared to normal controls. CONCLUSION: Overexpression of MACC1 and c-MET in retinoblastoma tissues, specifically those with risk factors for metastasis, suggests its role in proliferation and possibly in invasion. However, the current data do not support it to be a clinical prognostic marker in retinoblastoma tumours. The inverse serum expression is an intriguing finding, which warrants further studies especially in retinoblastoma.

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.