Macular corneal dystrophy with iridofundal coloboma in the same patient: a unique combination.

A young a presented with painless, progressive diminution of vision in both eyes (BE). Slit lamp examination revealed the presence of a single central corneal opacity in the right eye and multiple corneal opacities of varying sizes in the left eye (LE), limited to the anterior-mid corneal stroma. Microcornea with reduced central corneal thickness and complete inferonasal iris coloboma along with inferior fundal coloboma, sparing both the disc and macula, were noted in BE. A diagnosis of BE macular corneal dystrophy (MCD) and iridofundal coloboma (IFC) was made. The patient underwent LE sutureless anterior lamellar therapeutic keratoplasty. On histopathological examination, the excised corneal tissue revealed stromal lamellar disarray with positive colloidal iron staining, strongly suggestive of MCD. Whole-exome sequencing revealed the presence of a likely pathogenic carbohydrate sulfotransferase 6 (CHST6) mutation, confirming the diagnosis of MCD. This concurrent presence of IFC with a corneal stromal dystrophy is previously unreported in the literature, to the best of our knowledge.

Clinicodemographic profile of orbital exenteration in a tertiary eye care center - A 20-year experience.

PURPOSE: This study aimed to determine the clinical indications for orbital exenteration, demographic profile of these patients, and clinicopathologic correlations in the current times and to compare these results with previous published data. METHODS: It was a retrospective study. All exenterations performed at a tertiary eye care center over a period of 20 years (from January 2001 to June 2020) were retrospectively evaluated. Patient records were reviewed to obtain demographic data, presenting symptoms and their duration, laterality, and clinical and histopathologic diagnosis. RESULTS: A total of 352 cases (males:females = 222:130) who underwent exenteration were identified. Patients age ranged from 11 months to 87 years (mean: 43.86 years, median: 50 years). The most common indication for exenteration was found to be eyelid malignancy in 54.36%, followed by retinoblastoma in 18.75% and primary orbital tumors in 14.49%. Out of 156 cases of eyelid malignancies requiring exenteration, squamous cell carcinoma (SCC) was the most common histologic subtype ( n = 94, 60.26%), followed by sebaceous gland carcinoma ( n = 40, 25.64%) and basal cell carcinoma ( n = 20, 12.82%). The most common primary orbital tumors requiring exenteration were adenocystic carcinoma of the lacrimal gland in adults and rhabdomyosarcoma in the pediatric age group. Benign conditions requiring exenteration included fulminant fungal orbital infections and lymphangioma among others. CONCLUSION: The number of exenterations performed have significantly increased in terms of absolute numbers. However, the ratio of exenteration to other tumor-related surgeries, mainly excision biopsy, has reduced compared to that reported from a previous study. The most common indication in our study remains eyelid malignancy followed by intraocular malignancy. However, SCC has emerged as the most common tumor histologic subtype requiring exenterations.

Comparative posterior corneal profile of keratoconus hydrops versus Haab's striae in congenital glaucoma.

Keratoconus eyes develop corneal decompensation more often compared to eyes with primary congenital glaucoma (PCG) following Descemet's membrane (DM) tear. This study was conducted to compare the posterior corneal morphology in areas with DM breaks with regards to DM and pre-Descemet's layer (PDL) between the two. In this cross-sectional comparative study, anterior segment optical coherence tomography (AS-OCT) scans of the posterior cornea of advanced keratoconus eyes with hydrops ( n = 12), PCG eyes with Haab's striae ( n = 15), and healthy control eyes ( n = 14) were compared for DM-PDL morphology. These were further corroborated by the histopathology of corneal buttons from keratoconus ( n = 14) and PCG ( n = 13) cases obtained following penetrating keratoplasty and compared with controls (enucleated retinoblastoma globes, n = 6) on light microscopy and collagen IV immunostaining. AS-OCT showed a thicker median DM/PDL complex in PCG (80 µm) versus keratoconus eyes (36 µm, P = 0.01; Kruskal-Wallis test). The median height and length of detached DM-PDL were significantly more in keratoconus versus PCG (145 µm, 1766.1 ± 1320.6 µm vs. 26.5 µm, 453.3 ± 303.2 µm, respectively, P = 0.012; Kruskal-Wallis test). Type-1 DM/PDL detachment (seen as a characteristic taut chord) in keratoconus (90%) was the most common morphological pattern versus intracameral twin protuberance (92%) following DM breaks in PCG. Histopathology confirmed thicker DM in PCG (median: 63.4 µm) versus keratoconus eyes (median: 33.2 µm) or controls (27.1 µm) ( P = 0.001; Kruskal-Wallis test). Greater height/length of DM/PDL detachment compounded by poor healing response (lower DM/PDL thickness) probably causes more frequent corneal decompensation in keratoconus eyes when compared to PCG eyes following DM tears.

Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target.

Receptor tyrosine kinases (RTKs) serve as molecular targets for the development of novel personalized therapies in many malignancies. In the present study, expression pattern of receptor tyrosine kinases and its clinical significance in orbital RMS has been explored. Eighteen patients with histopathologically confirmed orbital RMS formed part of this study. Comprehensive q-PCR gene expression profiles of 19 RTKs were generated in the cases and controls. The patients were followed up for 59.53 ± 20.93 years. Clustering and statistical analysis tools were applied to identify the significant combination of RTKs associated with orbital rhabdomyosarcoma patients. mRNA overexpression of RTKs which included MET, AXL, EGFR was seen in 60-80% of cases; EGFR3, IGFR2, FGFR1, RET, PDGFR1, VEGFR2, PDGFR2 in 30-60% of cases; and EGFR4, FGFR3,VEGFR3 and ROS,IGFR1, EGFR1, FGFR2, VEGFR1 in 10-30% of cases. Immunoexpression of MET was seen in 89% of cases. A significant association was seen between MET mRNA and its protein expression. In all the cases MET gene expression was associated with worst overall survival (P = 0.03).There was a significant correlation of MET mRNA expression with RET, ROS, AXL, FGFR1, FGFR3, PDGFR1, IGFR1, VEGFR2, and EGFR3 genes. Association between MET gene and collective expression of RTKs was further evaluated by semi-supervised gene cluster analysis and Principal component analysis, which showed well-separated tumor clusters. MET gene overexpression could be a useful biomarker for identifying high risk orbital rhabdomyosarcoma patients. Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored.

Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma.

BACKGROUND: Pigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM. METHODS: Transmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers. RESULTS: Premelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression. CONCLUSION: Our results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.

HPV-Associated Squamous Cell Carcinoma of the Eyelid: Diagnostic Utility of p16 Immunohistochemistry and mRNA In Situ Hybridization.

BACKGROUND: High-risk (HR) Human papillomavirus (HPV) has been implicated in pathogenesis of squamous cell carcinomas (SCC) at several sites with mucocutaneous junctions, including the head and neck. SCC is the second most common eyelid malignancy. However, its association with transcriptionally active HR-HPV has not been adequately studied. METHODS: Two index cases of eyelid HPV-associated SCC are described in detail. A retrospective cohort of eyelid SCC was examined for p16 immunoexpression. Cases demonstrating p16 positivity or equivocal staining were subjected to high-risk HPV mRNA in situ hybridization (ISH). Quantitative real-time PCR (qPCR) was performed in mRNA ISH-positive cases for HPV genotyping. RESULTS: The two index patients were older adult females, with upper eyelid tumours. On histology, both tumours were non-keratinizing SCC with trabecular and nested architecture reminiscent of oropharyngeal HPV-associated non-keratinizing SCC, prompting p16 immunohistochemistry, which was positive. HR-HPV mRNA ISH was positive, and qPCR detected HPV16 in both cases. Three of 20 (15%) archival cases showed p16 immunopositivity and two (10%) showed equivocal staining. However, mRNA ISH was negative. All cases showing p16 immunostaining and lacking HR-HPV were keratinizing SCCs. Thus, 9% of all eyelid SCC examined demonstrated HR-HPV. CONCLUSION: The prevalence of HR-HPV in eyelid SCC is low in Indian patients. HPV-associated SCC may mimic commoner eyelid carcinomas as it lacks overt keratinization. In basaloid-appearing eyelid carcinomas, p16 immunopositivity should be followed by reflex HR-HPV mRNA ISH, as p16 immunohistochemistry alone has low specificity. The prognostic role, if any, of HPV association needs further evaluation.

Retinol palmitate in management of chronic Steven-Johnson Syndrome with ocular surface keratinization.

PURPOSE: To study the outcomes of topical Retinol Palmitate ophthalmic solution in chronic Stevens-Johnson Syndrome with ocular surface keratinisation. METHODS: It was a comparative interventional study conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2020 to 2022 evaluating outcomes of addition of topical Retinol Palmitate to conventional treatment objectively as well as subjectively from baseline up to 12 weeks. RESULTS: A statistically significant improvement was seen in patients who received topical Retinol palmitate at 12 weeks in terms of Schirmer-1 test(p=<0.01), tear prism height on ASOCT(p = 0.02), Rose Bengal staining score of cornea(p = 0.01) and conjunctiva (p < 0.01), reduction of ocular surface keratinisation on impression cytology(p = 0.01) and subjective evaluation using OSDI questionnaire(p = 0.04).Impression cytology revealed goblet cells in Retinol palmitate group at 1 week after initiation of therapy, which increased further at 1 month follow up but reduced at 3 months. No goblet cells were seen in control group at any follow-up. No significant difference was noted between the two groups in terms of visual acuity, tear film breakup time, inflammatory cells on impression cytology and inflammatory markers in tears. CONCLUSION: Topical Retinol palmitate is a safe and effective drug in cases of chronic SJS with ocular surface keratinisation. It has the potential to reverse keratinisation of the ocular surface and promote development of goblet cells. However, the survival of goblet cells is not long lasting.

Bilateral post-LASIK exacerbation of granular corneal dystrophy with epithelial ingrowth.

A male patient in his 30s, with a history of bilateral microkeratome-assisted myopic laser-assisted in situ keratomileusis (LASIK) 8 years ago at another centre, presented to us with gradually progressive diminution of vision and glare in both eyes for the last 4 years. On presentation, uncorrected distance visual acuity (UDVA) was 6/24 and 6/15 in the right eye and left eye, respectively, with normal intraocular pressures. Slit-lamp examination and anterior segment optical coherence tomography revealed well-defined white deposits, limited to an area within the LASIK flap. The deposits were confluent, at the level of the LASIK flap interface, and few discrete opacities were present in the posterior stroma. His father also had a similar clinical picture in both eyes. A diagnosis of both eyes post-LASIK exacerbation of granular corneal dystrophy with epithelial ingrowth was made. He underwent right eye femtosecond laser-assisted sutureless superficial anterior lamellar keratoplasty. At 6-month follow-up, UDVA improved to 6/12 with graft clarity of 4+ and coexistent grade 1 epithelial ingrowth.

Transconjunctival excision of external angular dermoid cyst: A novel approach.

PURPOSE: To excise external angular dermoid cyst (EADC) by transconjunctival approach and compare the surgical outcomes with the standard transcutaneous approach. DESIGN: This was a prospective, pilot, interventional, comparative study. METHODS: Patients with EADC with no or minimal fixity to the underlying bone on palpation and limited to eyelid were recruited. Patients were randomized into 2 groups; group 1 included patients with transcutaneous approach, and group 2 included patients with transconjunctival approach. The parameters assessed were intraoperative complications, duration and ease of surgery, postoperative complications, and overall satisfaction. RESULTS: Six children with a painless, round lesion in outer aspect of eyelid were recruited in each group. None of the patients had any intraoperative or postoperative complications, including dysfunction of eyelid contour and fold, persistence or late occurrence of lateral eyelid droop, excessive or recurrence of swelling, and ocular surface problems, especially in group 2, but a skin scar though hidden was inevitable in group 1. The duration of surgery was comparable with better ease of surgery in group 1 and a gradual learning curve in group 2. The overall satisfaction scores were significantly better in group 2 (p < 0.0001). In group 1, parents of 5 of 6 patients had to be reassured that the skin scar will fade with time. CONCLUSION: Transconjunctival excision of EADC is a viable and novel approach in patients with mobile cyst that is limited to the eyelid with no obvious bony fossa. Main limitations of the approach are that it requires surgical expertize, provides less surgical space, and has a gradual learning curve.

Establishment of patient-derived xenografts of retinoblastoma and choroidal melanoma on the avian chorioallantoic membrane.

Purpose: To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient-derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity. Methods: Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient-derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor-embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion. Results: Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross-sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki-67 positivity in Immunohistochemistry (IHC). Conclusion: The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient-specific tumors for preclinical drug screening.

Implications of LAG3 and CTLA4 immune checkpoints beyond PD-1/PD-L1 as a potential target in determining the prognosis of uveal melanoma patients.

BackgroundResponse rate of PD-1/PD-L1 immunotherapeutic blockade agents in uveal melanoma (UM) is poor. Lymphocyte activation gene 3 (LAG3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are the two promising immune checkpoint targets. Therefore, our aim was to explore at how these proteins were expressed in tumour tissue and serum, as well as their prognostic implications in UM. METHODS: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was determined by immunohistochemistry in 54 enucleated UM tissue samples. mRNA expression level of LAG3 and CTLA-4 was determined by quantitative real-time PCR and corroborated by western blotting. Furthermore, soluble form of LAG3, CTLA-4 and CCR8 expression in serum was measured in 40 UM patients using ELISA. RESULT: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was observed in 30%, 33%, 41%, 35%, 50% and 39% of the cases, respectively. Loss of nBAP1 expression was significantly correlated with CD8+expression (p=0.012) but not with tumour infiltrating lymphocytes. LAG3 and CTLA-4 mRNA levels were higher in UM compared with normal uveal tissues. Higher LAG3 expression with CD8+expression was associated with lower metastasis-free survival (MFS) (p=0.049), but not with CTLA-4 in UM patients. MFS rate was reduced in patients having lower levels of CCR8 protein (p=0.050) and increased level of LAG3 protein (p=0.001). CONCLUSION: Our findings suggest that higher levels of LAG3 in UM with histopathologically high-risk parameters predict high metastatic potential and that it could be used as a targeted immunotherapy alone or in combination with PD-1/PD-L1 blockade agents.

Small cell neuroendocrine carcinoma with primary orbital involvement - The unseen, and a review of literature.

Neuroendocrine neoplasms are derived from the epithelial lineages mainly of respiratory tract, with predominant neuroendocrine differentiation. There are only a handful of documented cases of paranasal small cell neuroendocrine carcinomas (SNEC) with primary orbital involvement. Here, the authors describe a 33-year-old male patient with rapidly progressive swelling of the right lower lid with proptosis since 4 weeks. On contrast-MRI orbit, an ill-defined multilobulated mass measuring 3.6 × 3.1 cm with intense homogenous enhancement was seen in the right retrobulbar space involving the right ethmoid sinus. On incisional biopsy, a poorly differentiated mass containing numerous small round blue cells and scanty intervening stroma with prominent necrosis and apoptosis was seen. Immunohistochemistry was strongly positive for synaptophysin. He was diagnosed as a case of SNEC and received chemotherapy, with good response till date of 9 months of follow up. The authors present a literature review and describe challenges in management of a primary orbital SNEC.

Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients.

Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (p < 0.05). On Kaplan-Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. RESULTS: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. CONCLUSION: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome.

PURPOSE: Molecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance. METHODS: In this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes. RESULTS: MMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050). CONCLUSION: Our findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.

Clinical and diagnostic imaging profile of three anterior segment dysgenesis disorders presenting with infantile corneal opacities.

PURPOSE: To describe three anterior segment dysgenesis disorders with infantile corneal opacities, namely, congenital hereditary endothelial dystrophy (CHED), primary congenital glaucoma (PCG), and Peters anomaly (PA) in terms of clinical characteristics, histopathology, genetic association, and diagnostic imaging profiles using imaging modalities such as ultrasound biomicroscopy (UBM) and microscope-integrated intraoperative optical coherence tomography (i-OCT). MATERIALS AND METHODS: Seventy-four eyes with 22 eyes of CHED, 28 eyes of PA, and 24 eyes of PCG were clinically evaluated and underwent imaging using UBM and i-OCT. Corneal buttons of 16 operated patients underwent histopathological analysis, while genetic analysis was done in 23 patients using whole-exome sequencing. RESULTS: Corneal diameters (CD) and UBM parameters like anterior chamber depth (ACD), iris thickness (IT), and ciliary body (CB) thickness revealed a statistically significant difference between the three categories. In PA, 9 eyes had a third rare phenotype with only a posterior corneal defect with no iris adhesions. Genetic mutations were seen in all tested patients with CHED, in 83.3% of patients with PCG, and in 80% of patients with the third type of PA. i-OCT helped in the characterization of corneal opacity, identification of posterior corneal defects, iridocorneal adhesions, and contour of Descemet's membrane. CONCLUSION: Overlapping phenotypes of the above disorders cause a diagnostic dilemma and parameters like CDs, UBM ACD, IT, and CB thickness help differentiate between them. i-OCT can help in classifying the diseases in a high resolution, non-contact manner, and can better delineate corneal characteristics. The rare third type of PA phenotype may have a genetic association.

Ocular surface characteristics in pediatric vernal keratoconjunctivitis: a clinico-cytological study.

PURPOSE: To compare the ocular surface parameters of children with vernal keratoconjunctivitis (VKC) with those of healthy controls and to correlate cytological characteristics with clinical findings and disease severity. METHODS: Newly diagnosed cases of VKC, not currently being treated, were recruited, along with age-matched controls with no ocular comorbidities. The Ocular Surface Disease Index questionnaire (OSDI) was administered to all children. Slit lamp biomicroscopy for meibomian gland dysfunction and ocular surface analysis was performed, including tear meniscus height, noninvasive tear film break-up time, lipid layer thickness, meibomian gland morphology, and meibomian gland duct distortion on meibography imaging. Conjunctival impression cytology was also performed. RESULTS: A total of 68 VKC patients and 33 controls were included. Statistically significant difference was seen in the mean OSDI score (30 ± 13.7 vs 16.1 ± 3 [P ≤ 0.01]), lipid layer thickness (24.2 ± 7.9 nm vs 69.9 ± 15.1 nm [P <0.001]), and noninvasive tear film break-up time (6.8 ± 1.7 vs 12.5 ± 1.8 sec [P < 0.01]) between groups. Mean tear meniscus height was 0.22 ± 0.06 mm in the VKC and 0.24 ± 0.04 mm in the control group (P = 0.096). Significant association was seen between grade of squamous metaplasia and severity of VKC (P < 0.01). Severity of VKC was found to be positively correlated with OSDI score (r = 0.767), grade of squamous metaplasia (r = 0.64) and negatively correlated with noninvasive tear film break-up time (r = -0.468), and lipid layer thickness (r = -0.253). CONCLUSIONS: This study highlights the poor ocular surface health of children with VKC, with severe disease being associated with worse forms of dry eye disease.

Tubercular DNA PCR of ocular fluids and blood in cases of presumed ocular tuberculosis: a pilot study.

Background: The definitive diagnosing of ocular tuberculosis (TB) is difficult; therefore, there is a need of better understanding of investigating TB DNA in presumed ocular TB patients. Objectives: The aim of this study is to correlate tubercular DNA PCR of aqueous/vitreous and blood in cases of presumed ocular TB. Design: A prospective study. Methods: DNA was extracted from aqueous of cases of choroidal tuberculoma (group 1) and serpiginous choroiditis (group 2) and from vitreous of cases of vasculitis (group 3) and macular hole/retinal detachment (group 4). Gel-based PCR and real-time PCR amplification were performed using IS6110 primer on ocular fluids. The same was also performed on the blood samples of cases in which tubercular DNA was detected in the ocular fluids. Results: Overall, 31 cases were analysed in our study. Tubercular DNA was detected in ocular fluids of seven cases: group 1, two cases (67%); group 2, one case (17%); group 3, four cases (27%); and no case of group 4. Blood samples of six of these seven patients were positive for tubercular DNA. Of these six patients, four had evidence of systemic TB and were on ATT. Two cases had no evidence of active systemic TB, yet PCR was positive from blood and ocular fluids. Conclusion: Tubercular DNA detected from ocular fluids may possibly be due to bystander DNA and may not indicate primary ocular tubercular infection. Thus, caution must be exercised prior to labelling a case of uveitis as being tubercular based on the results of molecular assays on ocular fluids alone. The results of PCR on ocular fluids should be correlated with PCR on blood and systemic findings.