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.

Outcomes of canalicular trephination versus canaliculodacryocystorhinostomy in common canalicular blocks.

AIM: This study aimed to compare the outcomes and efficacy of canalicular trephination with monocanalicular stenting and canaliculodacryocystorhinostomy (canaliculoDCR) with silicone intubation. MATERIALS AND METHODS: A prospective comparative study was done in 30 patients (30 eyes) with common canalicular blocks who were randomized into two groups. Fifteen patients underwent canalicular trephination with monocanalicular stenting and 15 patients underwent canaliculoDCR with silicone intubation. Common canalicular obstruction was diagnosed by preoperative syringing and the location of block was confirmed on probing. Stents were kept in both the groups for 3 months and followed up till 6 months postoperatively. Success was defined based on both anatomical and functional outcomes. Anatomical success was defined by the free passage of fluid on syringing with the fluid felt in the throat. Functional success was defined in terms of relief from epiphora based on the subjective opinion and its categorization by Kraft and Crawford's grading and the fluorescein dye disappearance test (FDDT). RESULTS: Eighty percent of eyes in canalicular trephination group and 73.3% of eyes in canaliculoDCR group were anatomically patent on syringing at the final follow-up. Sixty-six percent of eyes in trephination group and 53.3% in canaliculoDCR group were reported to have absent epiphora (complete recovery). Ten eyes in both groups had Grade 0 and 1 FDDT indicating a functional success of 66.6% in both groups. CONCLUSIONS: Canalicular trephination can produce results comparable to canaliculoDCR with silicone intubation in cases of common canalicular blocks. The average duration of surgery is significantly less in canalicular trephination which gives this procedure an added advantage.

Clinical features and orbital anomalies in Fraser syndrome and a review of management options.

Purpose: Fraser syndrome is a rare congenital disorder comprising cryptophthalmos, syndactyly, and many times, urogenital anomalies. Herein, the authors aimed to study and report the clinical features and orbital anomalies in cases diagnosed with Fraser syndrome. Methods: The authors retrospectively evaluated the records of patients with Fraser syndrome who had presented to a tertiary eye care hospital in northern India in the last 2 years (from January 2019 to December 2020). The clinical features were studied, entered in MS Excel, and the data was evaluated. Results: Data of 15 patients with Fraser syndrome were found. Majority of the patients were males and presented in the pediatric age group. Bilateral involvement was more common, and the most common variant of cryptophthalmos was abortive. Complete and medial madarosis of the eyebrows was the most common periocular finding. Complete cryptophthalmos was associated with cystic globes, whereas abortive forms had superior symblepharon. Common systemic features included syndactyly, bifid nose, and urogenital anomaly. Conclusion: Fraser syndrome is an extremely rare developmental disorder; it encompasses a wide range of ocular, periocular, and orbital anomalies, along with multiple pre-existing systemic anomalies. The treating ophthalmologist should always be careful in examining these patients.

Evaluation of lacrimal duct probing in adults with 0.02% and 0.04% mitomycin-C in primary acquired nasolacrimal duct obstruction: A randomized comparative pilot study.

PURPOSE: The purpose of the study is to evaluate the safety and efficacy of adjunctive use of mitomycin-C (MMC) using two different concentrations 0.2 mg/ml and 0.4 mg/ml for lacrimal duct probing to treat the nasolacrimal duct obstruction (NLDO) in adults. SUBJECTS AND METHODS: Prospective, an interventional comparative randomized pilot study of lacrimal duct probing conducted in the two study groups 0.02% MMC group (n = 30) and 0.04% MMC group (n = 30) in confirmed primary acquired NLDO of <1-year duration. Patency of lacrimal duct probing confirmed by syringing was compared at 1, 3, and 6-month follow-up in the two study groups, and corresponding subjective improvement of watering was appraised according to Kraft and Crawford grading. RESULTS: Patency of lacrimal duct probing in 0.02% MMC versus 0.04% MMC group was 66.66%/73.33% (P = 0.71) at 1 month, 46.66%/66.66% (P = 0.09) at 3 months and 46.66%/66.66% (P = 0.03) at 6-month follow-up, respectively. Subjective improvement of watering (no watering and mild watering) observed in 0.02% MMC versus 0.04% MMC group was 46.66%/73.33% (P = 0.03), at 1 month, 66.66%/83.33% (P = 0.13) at 3 months and 56.66%/73.33% (P = 0.17) at 6-month follow-up. CONCLUSION: Adult lacrimal duct probing with 0.04% MMC was associated with significant higher objective success rate than adult lacrimal duct probing with 0.02% MMC, without added concurrently side effects.

Orbital Aspergillosis, a great masquerader: a series of three unusual cases and a review of the literature.

Fungal infections of the orbit are infrequent. They typically affect immunocompromised individuals but, in some instances, can also affect an immunocompetent person. They mimic much orbital pathology clinically. Ours is a series of three patients eventually diagnosed with orbital aspergillosis but who, initially, were thought to have some other pathology.

Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1ɑ) in lacrimal gland Adenoid cystic carcinoma: Correlation with clinical outcome.

PURPOSE: VEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. METHODS: VEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. RESULTS: Immunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872-150.495; P = 0.012) was the most significant poor prognostic factor. CONCLUSIONS: This study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.

Prognostic impact of Notch1 receptor and clinicopathological High-Risk Predictors in lacrimal gland adenoid cystic carcinoma.

PURPOSE: Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features. METHODS: A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance. RESULTS: Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator. CONCLUSION: Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.

Tears of blood - a female adolescent with essential idiopathic bilateral haemolacria: case report and brief review.

Haemolacria is a rare condition that usually occurs secondary to a hidden pathology. On rare occasions when no underlying cause may be found, it is called essential idiopathic haemolacria. Here the authors report a case of a 13-year-old girl presented to the ophthalmology emergency department with spontaneous bloody tears from both eyes for the past six months. There was associated bleeding from the ear. The rest of the systemic and ophthalmology examinations were within normal limits. She was investigated systemically to look for any underlying pathology; however, her blood investigations, radiological imaging and local examinations performed by the Otorhinolaryngology, Ophthalmology, Gynaecology and Internal Medicine departments were all normal. A final diagnosis of bilateral essential haemolacria was made.

Large wooden orbital foreign body: case report and literature review.

Orbital trauma is often associated with foreign bodies. Wooden foreign bodies pose an urgent need for removal owing to their reactive nature and the high risk for infection. Though visual prognosis depends on associated ocular trauma, in selected cases, excellent visual and cosmetic outcomes are possible. An 18-year-old woman presented to our trauma facility with a history of fall directly onto a wooden stick from a height. On examination, there was a large wooden foreign body in the left medial orbit, extending into the ethmoidal sinus as visualised on imaging. After administration of perioperative antibiotics, the foreign body was removed in toto using careful tissue dissection and the soft tissue was closed in layers. Postoperatively at six months, the vision in the left eye was 20/20 with mild ptosis. Early surgery, careful dissection of soft tissues and adequate infection prophylaxis can lead to good outcomes in such cases.

Expression of BAP1 and ATM proteins: Association with AJCC tumor category in uveal melanoma.

BACKGROUND: Our aim is to detect the association of BAP1 with ATM protein with AJCC tumor category and its prognostic significance. METHODS: Based on AJCC tumor category, 69 patients samples were categorized into group A (LBD > 15 mm & tumor thickness ≥ 8 mm) and group B (LBD ≤ 15 mm & tumor thickness < 8 mm) subjected to immunohistochemistry to assess the nuclear expression of ATM and BAP1 proteins. Mutational analysis of BAP1 was performed on five samples from each group. RESULTS: Group A tumors showed insertion mutation of BAP1 gene while there was no mutation seen in group B tumor. At translational level loss of ATM and BAP1 was found in 65% and 66% of cases respectively. Loss of ATM with BAP1 was seen in 55% of cases which was more frequent in group A which was statically significant with metastasis (p = 0.006), advanced tumor staging (p = 0.021) and reduced metastasis-free survival (p = 0.048). On multivariate analysis loss of ATM along with BAP1 came out to be an independent prognostic marker (p = 0.035). CONCLUSION: Our data suggest that loss of BAP1 along with ATM might serve as a potential prognostic indicator in patients with an advanced AJCC tumor category, which leads to an increased risk of metastasis.

Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors.

PURPOSE: Uveal melanoma (UM) is an intraocular malignancy commonly arising from choroid which can cause visual loss or metastasis. Ataxia-telangiectasia mutated (ATM) protein is an activator of DNA damage response and its role in uveal melanoma (UM) is still unexplored. Therefore, the study aims to detect the expression and localization of ATM protein and its association with clinicopathological parameters METHODS: Expression of nuclear ATM (nATM) was investigated on 69 formalin fixed paraffin embedded choroidal melanoma samples by immunohistochemistry and validated by western blotting. Results were then correlated with clinical and histopathological parameters. Prognostic significance was determined by the Kaplan-Meier analysis and the multivariate analysis by Cox's hazard proportional method. RESULTS: Loss of nATM was observed in 65% of cases, which was statistically significant with the reduced disease-free survival (p = 0.042). This loss was more frequently found in cases with high-risk histopathological factors like epithelioid cell type, tumor infiltrating lymphocytes and high pigmentation which might help in the progression of melanoma. On multivariate analysis, extraocular spread and loss of nATM were found to be independent prognostic factors (p < 0.05). CONCLUSION: Our data suggest that loss of nATM protein might serve as a poor prognostic marker in the pathogenesis of uveal melanoma which may lead to increased risk of metastasis.

Expression of multidrug resistance proteins in retinoblastoma.

AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS: Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS: Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

ZEB2/SIP1 as novel prognostic indicator in eyelid sebaceous gland carcinoma.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and metastasis in various malignancies. ZEB2/SIP1 is an important EMT regulator and down-regulates E-cadherin expression. The present study was planned to explore status of EMT-associated markers ZEB2/SIP1 and E-cadherin in eyelid sebaceous gland carcinoma (SGC) and to correlate with clinicopathological high-risk features. Expressions of ZEB2 and E-cadherin were evaluated by immunohistochemistry in 65 cases of histopathologically proven eyelid SGC. The results were correlated with clinicopathological high-risk features and survival of the patients to determine the prognostic significance of ZEB2, E-cadherin, and various high-risk features. Cytoplasmic overexpression of ZEB2 and membranous loss of E-cadherin were seen in 68% and 66% of cases of eyelid SGC, respectively. ZEB2 overexpression was significantly associated with E-cadherin loss (P = .002). Overexpression of ZEB2 also showed significant association with lymph node metastasis (P = .046), orbital invasion (P = .049), large tumor size (P = .018), and advanced tumor stages (P = .036). Survival analysis revealed that patients with ZEB2 overexpression had poor survival. ZEB2 overexpression and orbital invasion were found to be independent prognostic indicators (univariate analysis). However, multivariate analysis showed that ZEB2 (hazard ratio, 0.094; 95% confidence interval, 00.012-0.709; P = .022) was the best poor prognostic indicator of eyelid SGC. Our study demonstrates the role of both ZEB2 and E-cadherin in the promotion of EMT in eyelid SGC. The outcome of this study also points toward ZEB2 as an independent prognostic marker as well as a potential therapeutic target in eyelid SGC.

Modified technique of levator plication for the correction of Marcus Gunn jaw-winking ptosis: a case series.

To conduct a study on ptotic eyelids with Marcus Gunn jaw-winking ptosis operated via a technique of modified levator plication, prospective interventional case series. Ten ptotic eyelids with Marcus Gunn jaw-winking phenomenon (MGJWP) underwent modified levator plication surgery. Postoperatively, all cases were followed up for at least 6 months. Outcome parameters included amount of ptosis correction, amount of MGJWP correction, palpebral aperture height, lid lag, and lagophthalmos. The mean amount of ptosis was 4.25 ± 0.79 mm (range of 3-6 mm), mean amount of MGJWP was 5.10 ± 2.27 mm (range 2-9 mm), and the mean levator function was 8.3 ± 2.27 mm (range of 4-12 mm). At 6 months follow-up, good correction of ptosis was seen in nine out of ten patients. Resolution of MGJWP (≤1 mm of excursion of upper eyelid with synkinetic mouth movement) was seen in three patients. Improvement in MGJWP (>1 mm of excursion of upper eyelid with synkinetic mouth movement) was seen in seven patients. The mean post-operative lagophthalmos was 0.80 ± 0.88 mm. The modified levator plication technique was effective in the treatment of MGJWP. This modified technique of levator plication is anatomically less destructive and hence more acceptable, with the added advantages of less post-operative lagophthalmos and no lid contour defects.

Expression of P-glycoprotein in human retinoblastoma and its clinical significance.

Retinoblastoma is the most common malignant intraocular tumor of childhood. Drug resistance and relapses are major problems with chemotherapy, which is regarded as the mainstay of globe preserving treatment in retinoblastoma. P-glycoprotein (P-gp) expression has been reported to be associated with chemoresistance and poor prognosis in various malignancies. We analyzed P-gp expression in retinoblastoma specimens, enucleated either primarily or after neoadjuvant chemotherapy by immunohistochemistry and immunoblotting, and correlated with the histopathological findings. Variables were statistically analyzed by Fischer's exact and chi-square tests. Tumor tissues were collected from enucleated eyes of 24 children. Fifteen of these were primarily enucleated (group I), and nine (group II) had received chemotherapy prior to enucleation. P-gp was expressed in 4/15 (26.7 %) eyes in group I and in 5/9 (55.6 %) eyes in group II. P-gp was highly expressed in group II as compared to group I. There was no correlation between P-gp expression and tumor differentiation, invasion, or laterality. In conclusion, there was markedly high expression of P-gp in eyes with retinoblastoma enucleated after chemotherapy. This may possibly play a role in chemoresistance or it may be that chemotherapy might have induced high expression. These findings may have important implications for the treatment of retinoblastoma patients but need further prospective investigations in a larger patient population.

Human papillomavirus: a predictor of better survival in ocular surface squamous neoplasia patients.

BACKGROUND: Although human papillomavirus (HPV) has been implicated in the pathogenesis of ocular surface squamous neoplasia (OSSN), no study has so far dealt with the prognostic role of HPV. In this study the presence and significance of HPV in OSSN and its correlation with p16(INK4a) immunoexpression was determined. METHODS: HPV was detected by HPV-L1 capsid gene-specific multiplex PCR using PGMY09/11 primers, and genotyping was done by linear array on 64 OSSN patients and 15 conjunctival controls. p16(INK4a) immunoexpression as a marker for HPV presence was also evaluated. RESULTS: The HPV genome was detected in 11% of cases by multiplex PCR, and all positives belonged to a high-risk HPV16 genotype. p16(INK4a) Overexpression was seen in 28% (18/64) of cases. Control conjunctival tissues were negative for HPV and p16(INK4a) expression. The presence of HPV was associated with significantly improved disease-free survival (p=0.02) as well as p16(INK4a) overexpression (p=0.001). The sensitivity and specificity of p16(INK4a) as a marker for HPV presence was 86% and 79%, respectively, with a positive predictive value of 33% and a negative predictive value of 98%. CONCLUSIONS: The results of this study point towards HPV as a predictor of better survival in a subset of HPV-positive OSSN patients. Although p16(INK4a) immunoexpression is a useful indicator of HPV presence in OSSN, confirmation by multiplex PCR is necessary.

A histopathologic analysis of eyes primarily enucleated for advanced intraocular retinoblastoma from a developing country.

CONTEXT: In eyes enucleated for retinoblastoma, presence of histopathologic high-risk factors is associated with a higher risk of local recurrence and systemic metastasis. OBJECTIVE: To evaluate histopathologic features in children with retinoblastoma in our population and establish relationship between age, tumor differentiation, and high-risk features. DESIGN: Retrospective histopathologic analysis of 609 consecutively enucleated eyes for advanced intraocular retinoblastoma during a 10-year period. A nonparametric test was used to establish relationship between age, differentiation, and high-risk features. RESULTS: Poorly differentiated retinoblastoma presented in 80.3% and well-differentiated in 19.7% of eyes. Well-differentiated tumors presented earlier (median 1.2 years) than poorly differentiated tumors (median 2.5 years) (P < .001). One hundred fourteen eyes (18.7%) had 1 and 138 (22.7%) had at least 2 high-risk histopathologic factors. Invasion of anterior chamber was found in 10.0%, iris in 10.7%, ciliary body in 6.7%, sclera in 13.7%, massive choroid in 24.6%, postlaminar optic nerve in 16.1%, resected margin of the optic nerve in 7.4%, and extrascleral tissue in 4.1% of eyes. Extensive necrosis was seen in 31.0% of eyes. Poorly differentiated tumors were significantly associated with presence of more than 1 high-risk histopathologic feature (P < .001) and extensive necrosis (P < .001). CONCLUSION: Poorly differentiated tumors present at a later age and are associated with presence of multiple high-risk factors and extensive necrosis. In our population, high-risk histopathologic factors are present in a significant number of eyes. Because we have included only primarily enucleated eyes, this could truly represent the distribution of high-risk histopathologic factors in children with retinoblastoma.