Clinical spectrum and clinicopathological correlation of pediatric orbital tumors: 20 years' experience from a tertiary eye care center.

PURPOSE: To study the epidemiological profile of various pediatric orbital tumors and determine their clinicopathological correlation over 20 years. METHODS: A retrospective analysis of all pediatric patients with orbital tumors from the medical records between 1995 and 2015 was done. Tumors were categorized based on their cellular origin. Demographic details, clinical and histopathological diagnoses, frequency, and clinicopathological correlation were studied. RESULTS: A total of 265 pediatric patients with orbital tumors were analyzed, of which 145 (54.7%) patients were males and 120 (45.3%) were females. The mean age was 7 years (median: 6 years; range: 10 days-16 years). The distribution of lesions in each group was as follows: vasculogenic, 76 (28.7%); lipogenic and myxoid, 66 (25%); myogenic, 31 (11.7%); optic nerve and meningeal, 22 (8.3%); lymphoid and lymphoproliferative, 18 (6.8%); secondary orbital tumors, 14 (5.2%); histiocytic, 9 (3.4%); miscellaneous, 9 (3.4%), lacrimal gland, 8 (3%); mesenchymal with neural differentiation, 6 (2%); osseous, 4 (1.5%), and fibrocystic, 2 (0.8%). The most common benign and malignant pediatric orbital tumors were dermoid cysts (65, 24.5%) and rhabdomyosarcoma (31, 11.7%). A statistically significant ( P < 0.0001) clinicopathological correlation was observed in 208 (83.2%) out of 250 biopsy-proven cases. CONCLUSION: Pediatric orbital neoplasms include a broad spectrum of benign and malignant lesions. Vasculogenic tumors constitute the majority of them, followed by lipogenic and myxoid tumors. A thorough knowledge of the incidence, clinical profile, imaging features, and histopathology of specific orbital tumors aids in accurate diagnosis and their successful management.

Integrative management of anaplastic astrocytoma through a combination of Ayurveda and conventional care: A case report.

Anaplastic Astrocytoma (AA) is a relatively rare cancer, and is associated with a median life expectancy of 3 years after conventional therapy. Complete cure of the highly infiltrative AA is uncommon, and reports of positive outcome in cases of partial resection of AA are rare. Further, integrative approaches to the management of AA remain underexplored. This paper contributes to the limited literature in this domain by presenting a case that was successfully treated through integrative conventional and Ayurvedic interventions. A patient diagnosed with AA in the left parieto-occipital lobe underwent partial lesion resection followed by post-operative radiation and chemotherapy. The patient was given a conservative post-surgical life expectancy of two years, and was referred to an Ayurveda hospital for further treatment. The Ayurvedic intervention was focussed on redressal of radiation and chemotherapy side-effects, improvement of quality of life, and improving the patient's strength and immunity. Following this novel integrative model of care, the patient was able to resume all personal and professional routines, and a contrast MRI revealed absence of residual lesion allowing the patient to outlive his initial prognosis by several years till date. We posit that the findings of this report merit further examination in the interest of potential improvements to existing models of care.

The undesirable wink.

Background: Marin-Amat syndrome is a rare acquired oculofacial synkinesis first reported in 1918. It manifests as involuntary eyelid closure on jaw opening or on lateral movement of the jaw following a peripheral facial nerve palsy. The increased orbicularis tone due to aberrant connections between the cranial nerve (CN) V and CN VII results in an undesirable wink with major psychosocial impact. Purpose: Most cases in literature were either observed or administered botulinum toxin injection to the orbicularis muscle. There are few sporadic reports of surgical interventions with successful outcomes.Hence there was a need to generate awareness regarding various modes of management of this rare entity. Synopsis: We present a video on the clinical presentation and management of six such patients, of whom one was bilateral. Five patients were females. Traumatic facial nerve paralysis and Bell's palsy was previously diagnosed in one and five patients respectively. The mean age was 52 ± 9.48 years. The mean MRD (margin reflex distance) 1 and MRD 2 was 3.17 ± 0.60 and 5.33± 0.65 mm respectively. On smiling or on movement of the jaw the MRD 1 and 2 was reduced by 2. 50±0.40 and 1.50+/-0.40 mm respectively. Of the six patients four patients opted for nil intervention. Highlights: Botulinum toxin injection and preseptal orbicularis resection in the upper and lower eyelid along with blepharoplasty was performed in 1 patient each. Satisfactory reduction in the synkinetic movement was achieved in both. Marin-Amat syndrome is a rare often underdiagnosed synkinetic disorder following peripheral facial nerve palsy. Botulinum toxin injection and preseptal orbicularis resection are viable management options. Video link: https://youtu.be/YQbRecp449w.

The spectrum and clinicopathological correlation of eyelid lesions: Twenty years' experience at a tertiary eye care center in South India.

PURPOSE: : To study the epidemiological pattern and diagnostic accuracy of histopathologically proven eyelid lesions over a period of two decades. METHODS: : A retrospective study of all histopathologically proven eyelid lesions from April 1996 to March 2016 was conducted. The lesions were broadly categorized as benign or malignant. Inflammatory and infectious lesions were included under the benign category. The percentage and diagnostic accuracy of each lesion was calculated. RESULTS: : There were a total of 994 (M = 551, F = 443) cases. The mean age of the patients was 43.5 ± 19.9 years. There were 809 (81.4%) benign and 185 (18.6%) malignant lesions. Benign lesions were commonly seen in the fourth decade, while the malignant ones in the late fifth decade. The upper lid was the most common site in both groups (n = 481, 48.4%). The commonest benign lesion was chalazion (n = 484, 59.8%). Dermal nevus (n = 94, 11.6%) was the most common benign neoplasm, while Molluscum contagiosum (n = 25, 3.09%) was the most common infectious lesion. Sebaceous gland carcinoma (SGC) (n = 103, 55.7%) was the leading malignant lesion followed by basal cell carcinoma (n = 39, 21.1%). Eleven malignant cases were misdiagnosed as benign (5.9%). Chalazion (99.1%) and SGC (65%) had the highest diagnostic accuracy, while Molluscum (40%) and squamous cell carcinoma (40%) were the most misdiagnosed lesions in the respective groups. CONCLUSION: : Benign eyelid lesions are far more common than malignant ones. Atypical and rare presentations may lead to misdiagnosis. Knowledge of epidemiological patterns and clinical features can help in achieving higher diagnostic accuracy.

Orbital and adnexal amyloidosis: Thirty years experience at a tertiary eye care center.

Purpose: The aim of this work was to study the clinical presentation, management and outcomes of orbital and adnexal amyloidosis. Methods: This retrospective analysis included all the patients diagnosed with orbital and adnexal amyloidosis between January 1990 and December 2019. Positive staining with Congo Red and apple-green birefringence on polarized light microscopy established the diagnosis. Data analyzed included demographic profile, varied presentations, management, and outcome. Results: Thirty-three eyes of 26 patients were included. The male:female ratio was 1:1. The mean age of the study population was 42.6 ± 16 years. The median duration of symptoms was two years. Unilateral involvement was seen in 19 eyes (right = 11, left = 8). The most common presenting feature was acquired ptosis. Eyelid was the most commonly affected site followed by orbit and conjunctiva. Two patients had systemic involvement in the form of multiple myeloma and lymphoplasmacytic lymphoma. Complete excision was done in seven (26.9%) cases while 19 (73.1%) cases underwent debulking. Three patients underwent ptosis surgery. The median duration of follow-up was 1.5 years. Three cases had recurrence and underwent repeat surgery. Conclusion: Orbit and adnexa is a rare site for amyloidosis. It is usually localized; however it can occur as a part of systemic amyloidosis. Eyelid is the most common site of involvement and patients usually present as eyelid mass or ptosis. Complete excision is difficult and most of the patients usually undergo debulking surgery. All patients should undergo screening for systemic amyloidosis.

Complete Excision of Intradural-Extraforaminal Spinal Tumors Using a Minimally Invasive 2-Incision Technique With Fixed Tubular Retractors.

Spinal tumors are rare, of which intradural-extramedullary lesions form the majority of primary spinal tumors. Occasionally these may even be large, dumbbell shaped, with both intraspinal and extraspinal components. Complete gross total resection is the gold standard in the removal of these tumors since most are benign in nature. Traditionally this has been achieved using large open midline approaches that involve significant muscle dissection, extensive laminectomy, and even facetectomy. This may lead to instability, requiring stabilization to prevent deformity. Minimally invasive surgical approaches using fixed tubular retractors may obviate this need by minimizing the amount of muscle stripping and bony resection required for complete tumor excision. By utilizing facet sparing corridors, the authors describe a novel 2-incision minimally invasive surgical technique that combines a paramedian and a far-lateral approach to access both the intraspinal and extraforaminal, paraspinal portions of the tumor for achieving complete excision. Three illustrative cases are discussed with tumors in 2 different spinal locations that highlights the versatility of this technique-1 in the cervical region and the other 2 in the thoracolumbar region.

Carvacrol Promotes Cell Cycle Arrest and Apoptosis through PI3K/AKT Signaling Pathway in MCF-7 Breast Cancer Cells.

OBJECTIVE: To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells. METHODS: MTT and lactate dehydrogenase assays were performed with cells treated with different doses of carvacrol (0-250 p mol/L) at different time points (24 and 48 h). The nuclear morphology was assessed in MCF-7 cells with propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining and analyzed by fluorescence microscopy. Events like cell cycle arrest, apoptosis was observed by flow cytometric analysis and expressions of p-Rb, cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6, Bax, Bcl-2, PI3K/p-AKT was analyzed by immunoblot. RESULTS: Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h (P<0.05). importantly, there was a significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells (P<0.05 or P<0.01). A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest (P<0.05 or P<0.01). In addition, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions. Further, Annexin V/PI staining by FACS analysis, dual staining by AO/EB and PI staining studies suggests induction of apoptosis by carvacrol through PI3K/Akt signaling pathway in MCF-7 cells. CONCLUSION: Carvacrol significantly inhibited the breast cancer MCF-7 cell proliferation and induced apoptosis via suppressing PI3/AKT signaling pathway.

Combined medical and surgical management for cicatricial ectropion in lamellar ichthyosis: A report of three cases.

Ichthyosis is a rare inherited skin disorder characterized by abnormal keratinization of the epidermis. Cicatricial ectropion is the most common ophthalmic feature of congenital ichthyosis. Progressive subepithelial cicatrization and abnormal cornification of eyelid skin cause progressive ectropion in both eyelids, leading to lagophthalmos and corneal exposure. Surgical correction of cicatricial ectropion in these cases is challenging with unsatisfactory results. Proper processing of the donor and recipient site with lubricants and topical retinoids before surgery makes grafting easier and its survival better. We present three cases of lamellar ichthyosis with cicatricial ectropion managed with combined preoperative topical therapy followed by surgery. All patients had extremely good surgical outcomes, with none of them requiring repeat surgery.

Clinical spectrum and management outcomes of Langerhans cell histiocytosis of the orbit.

Purpose: To describe the clinical spectrum and management outcomes of Langerhans cell histiocytosis (LCH) involving the orbit. Methods: Retrospective review of patients with orbital LCH presenting at the Sankara Nethralaya, Chennai, India, over the past 15 years. Demographic details, presenting features, radiology, histopathology, immunohistochemistry, and management outcomes were analyzed. Results: Nine patients were reviewed. The mean age of presentation was 10.12 ± 14.31 years (range: 6 weeks to 35 years). Eyelid swelling was the most common presenting feature (4, 44.4%), followed by proptosis (3, 33.3%). The mean duration of the presentation was 2.21 ± 2.77 months. Radiological investigations revealed orbital roof osteolytic defects in six (66.6%) patients. Six patients underwent near-complete excision of the mass while three underwent incisional biopsy. Histopathology revealed histiocytes with nuclear grooving and numerous eosinophils characteristic of LCH. The cells were positive for CD1a and S 100 antigens. None of the patients had any systemic involvement. Three received systemic steroids and four received systemic chemotherapy. At a mean follow-up of 17.85 ± 23.46 months, all had complete remission without any signs of recurrence. One patient was lost to follow-up after near-complete excision while one adult patient with a mass in the intraconal space had no recurrence after near-complete excision. Conclusion: LCH is a rare disorder of the orbit that commonly occurs in children and should be considered a differential for osteolytic lesions involving the orbit. All patients should undergo a systemic evaluation to rule out multifocal disease. The treatment depends upon disease extent and risk factors.

Periocular Basal Cell Carcinoma: 20-Years Experience at a Tertiary Eye Care Center of South India.

PURPOSE: To study the clinical profile and management outcomes of periocular basal cell carcinoma (BCC). MATERIALS AND METHODS: A retrospective analysis of all histopathologically proven cases of BCC between 1995 and 2015 was done. The demographic data, clinical presentation, histopathological subtype, and management outcomes were analyzed. RESULTS: We had a total of 185 malignant eyelid tumors during the study period, out of which 37 (20%) were BCC. Thirty-two (86.5%) out of 37 cases were primary BCC. The mean age was 63.3 years. Pigmented ulcerative lesion (14, 38%), lower eyelid (19, 51%), and nodular BCC (15, 40%) were the most common presentation, periocular site, and histological subtype, respectively. 28 patients underwent excision under frozen section with an average tumor-free margin of 3.5 mm. Mean follow-up period was 18.78 months. Recurrence rate of 0% and 3.1% was noted in primary and recurrent BCC, respectively. CONCLUSION: Periocular BCC commonly presents as pigmented ulcerative lesion in the lower lid. Excision biopsy under frozen section with an average tumor-free margin of 3.5 mm offers cure in most cases.

Keratoprosthesis: Current global scenario and a broad Indian perspective.

Keratoprosthesis (Kpro) forms the last resort for bilateral end-stage corneal blindness. The Boston Type 1 and 2 Kpros, the modified osteo-odonto Kpro and the osteo-Kpro are the more frequently and commonly performed Kpros, and this review attempts to compile the current data available on these Kpros worldwide from large single-center studies and compare the indications and outcomes with Kpros in the Indian scenario. Although the indications have significantly expanded over the years and the complications have reduced with modifications in design and postoperative regimen, these are procedures that require an exclusive setup, and a commitment toward long-term follow-up and post-Kpro care. The last decade has seen a surge in the number of Kpro procedures performed worldwide as well as in India. There is a growing need in our country among ophthalmologists to be aware of the indications for Kpro to facilitate appropriate referral as well as of the procedure to enable basic evaluation during follow-ups in case the need arises, and among corneal specialists interested to pursue the field of Kpros in understanding the nuances of these surgeries and to make a judicious decision regarding patient and Kpro selection and more importantly deferral.

Mesenchymal chondrosarcoma of the orbit: A case report with 5 years of follow-up.

Mesenchymal chondrosarcoma is a rare orbital tumor. Several case reports of this rare tumor have been published in the literature but only 6 cases have documented a follow up of 5 years or more. We report a case of 28 year-old female who presented with left orbital mass. Computed Tomography (CT) revealed a lobulated mass in the superior extraconal space with dense intralesional calcification. Patient underwent complete resection of the mass and histopathology was suggestive of mesenchymal chondrosarcoma. He was given adjuvant radiotherapy and there was no recurrence or metastasis at 5 years of follow-up. The case highlights that a complete resection with adjuvant radiotherapy in cases of orbital mesenchymal chondrosarcoma offers excellent prognosis.

Orbital angioleiomyoma: A rare orbital neoplasm.

A 44-year-old male patient presented with painless progressive proptosis of left eye for the last 20 years. Examination revealed a purplish vascular mass extending from the medial orbital region to the surface of the globe. He underwent complete excision of the mass via an anterior orbitotomy approach. Histopathology and immunohistochemistry revealed a diagnosis of angioleiomyoma. No recurrence was noted at 1 year of follow-up. Angioleiomyomas are benign smooth muscle tumors with an additional vascular component. Their occurrence in the orbit is extremely rare with only three cases reported in literature till date. We report a fourth case of angioleiomyoma of the orbit with the longest duration of presentation of 20 years.

Large lamellar corneoscleral grafts: tectonic role in initial management of severe ocular chemical injuries.

PURPOSE: To report the outcome of large tectonic lamellar grafts in cases of severe chemical injury associated with corneal melt/perforation and scleral ischemia, with or without retinal detachment. METHODS: This was a retrospective interventional analysis of 7 eyes of 6 patients within 3 months of injury with simultaneous/subsequent surgical procedures to salvage globe integrity. RESULTS: Of 7 included eyes, both eyes of one patient underwent phthisical changes. In one eye, the retinal detachment was inoperable; in another, the retina was reattached with silicone oil tamponade, and underwent subsequent Boston type 1 keratoprosthesis with a final best-corrected visual acuity of 20/80 at 3-year follow-up. One eye underwent Lucia type 2 keratoprosthesis, one eye the modified osteo-odonto keratoprosthesis procedure, with visual recovery of 20/120 and 20/80, respectively, and one maintained vision of 20/200 for 2 years following a penetrating keratoplasty. The final best-corrected visual acuity was better than 20/200 in 4 out of these 7 eyes (57.14%). CONCLUSIONS: In acute severe chemical injuries, corneal perforation with scleral ischemia can threaten globe integrity as well as preclude routine tectonic penetrating procedure. Presence of a concurrent retinal detachment in this setting further complicates the approach as well as the outcome. The use of a large tectonic corneoscleral lamellar graft provides a viable option in the achievement of tectonic stability in these eyes, facilitating future visual rehabilitative procedures.

Intracerebellar malignant nerve sheath tumor in a child: case report and review of literature.

PURPOSE: Intracerebellar malignant nerve sheath tumor (ICMNST) is an extremely rare entity, only two cases have been reported previously, and this is the first case to be reported in a child. The histogenesis, diagnosis, and management of this entity are very ambiguous, and natural history in a child is unknown. METHODS: The authors report a 7-year-old girl who presented with ataxia and signs of raised intracranial pressure and discuss the challenges in diagnosis, surgical strategy, and treatment. RESULTS: Following gross total resection and radiation to tumor bed, the patient had unremarkable recovery and is recurrence free at 1-year follow-up. CONCLUSION: ICMNSTs are extremely rare tumors of the cerebellum. Preoperative radiological diagnosis is not possible due to its close radiological resemblance to other common posterior fossa tumors. Immunohistochemistry plays a pivotal role in clinching the diagnosis. Though the reported adult counterparts have shown dismal prognosis, the pediatric counterparts may fare better with good surgical resection followed by radiotherapy.

Prediction of promiscuous epitopes in the e6 protein of three high risk human papilloma viruses: a computational approach.

A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, EpiJen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.

Cryptophthalmos: reconstructive techniques--expanded classification of congenital symblepharon variant.

PURPOSE: To report the varied presentation and management of cryptophthalmos and further categorize grades of the congenital symblepharon variant based on the severity of the defect. METHODS: The records of 34 eyes of 25 patients with cryptophthalmos who sought treatment at the authors' tertiary eye care center over a period of 22 years were analyzed. RESULTS: Of the 34 eyes, 25 belonged to the congenital symblepharon variant, which could distinctively be further classified in medial/mild (4), moderate (9), and severe (11) subgroups and the surgical management for each has been outlined. The associated corneal and facial anomalies have also been highlighted along with their management modalities when indicated. CONCLUSIONS: Although a rare clinical entity, this is the largest series of cryptophthalmos reported so far with a proposed classification scheme for the congenital symblepharon variant.

Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome.

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.

Reconstructions of eyelid defects.

Eyelids are the protective mechanism of the eyes. The upper and lower eyelids have been formed for their specific functions by Nature. The eyelid defects are encountered in congenital anomalies, trauma, and postexcision for neoplasm. The reconstructions should be based on both functional and cosmetic aspects. The knowledge of the basic anatomy of the lids is a must. There are different techniques for reconstructing the upper eyelid, lower eyelid, and medial and lateral canthal areas. Many a times, the defects involve more than one area. For the reconstruction of the lid, the lining should be similar to the conjunctiva, a cover by skin and the middle layer to give firmness and support. It is important to understand the availability of various tissues for reconstruction. One layer should have the vascularity to support the other layer which can be a graft. A proper plan and execution of it is very important.