Association of fracture type with enophthalmos and intraorbital volume correction in orbital fractures: A computed tomographic study.

PURPOSE: To determine the influence of different types of orbital fractures on the radiographic post-treatment outcomes. METHODS: The investigation was a retrospective cohort study involving CT data of all patients who underwent delayed primary or secondary surgery for orbital/zygomatico-orbital trauma between 2019 and 2021. The sample was divided into three groups 1, 2, and 3: isolated floor, floor and medial wall, and combined orbit and zygomatic complex fractures. The type of orbital fracture was the exposure, while the outcome measures were reduction in enophthalmos and intraorbital volume and linear relationship between the two variables. Data were analyzed for variance between groups and association. Statistical significance was set at < 0.05. RESULTS: Forty-four patients (3 females and 41 males) with a mean age of 28.6 years were included in the study. Reductions in enophthalmos (P < 0.001) and intraorbital volume (P = 0.003) demonstrated significant variance between the groups. For every cubic centimeter of reduction in volume, the reduction in enophthalmos was 0.78 mm (P < 0.001) in isolated floor fractures, 0.60 mm (P = 0.013) in combined fractures involving the floor and medial walls, and 0.24 mm (P = 0.456) in combined fractures of the orbit and zygoma. CONCLUSION: Correction of enophthalmos strongly depends on the type of orbital fracture. There exists a significant linear relationship between enophthalmos and intraorbital volume in fractures involving the internal orbit.

Primary Leiomyosarcoma of the Orbit and Conjunctiva: A Report of Four Cases With a Review of the Literature.

Leiomyosarcomas (LMS) are common soft tissue tumors in the body. Primary orbital and conjunctival LMS are, however, rare. Herein, we describe the diverse clinical presentations, histopathological features, and management outcomes of three cases of primary LMS of the conjunctiva and one case of primary orbital LMS. The first patient was a 40-year-old female with primary orbital LMS who developed recurrence following wide local excision. The remaining three cases were primary conjunctival LMS. All four patients underwent orbital exenteration and were disease-free at a mean follow-up period of 18.64 months. LMS is known for local recurrences and metastasis. Complete surgical excision and prompt adjuvant radiotherapy can improve the prognosis.

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.

An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.

High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments. Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype (SASP) induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence. Moreover, senescent tumor cells could spur the growth of their non-senescent counterparts, thereby accelerating recurrence. In this review, we highlight emerging evidence supporting the use of senolytic agents to ablate latent, senescent-like cells that could contribute to tumor recurrence. We also discuss how senescent cell clearance can decrease the SASP within the tumor microenvironment thereby reducing tumor aggressiveness at recurrence. Finally, senolytics could improve the long-term sequelae of prior therapy on cognition and bone marrow function. We critically review the senolytic drugs currently under preclinical and clinical investigation and the potential challenges that may be associated with deploying senolytics against latent glioma. In conclusion, senescence in glioma and the microenvironment are critical and potential targets for delaying or preventing tumor recurrence and improving patient functional outcomes through senotherapeutics.

DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation.

The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.

A fungal epidemic amidst a viral pandemic: Risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis in India.

PURPOSE: To study the risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis (ROCM) during the COVID-19 pandemic in India. METHODS: Multi-centric retrospective case-control study conducted from October 2020 to May 2021. Cases comprised of consecutive patients of COVID-19-associated ROCM (CA-ROCM) presenting at the participating ophthalmic institutes. Controls comprised of COVID-19-positive or COVID-19-recovered patients who did not develop ROCM. Comparative analysis of demographic, COVID-19 infection, treatment parameters and vaccination status between cases and controls performed. Clinical and imaging features of CA-ROCM analyzed. RESULTS: There were 179 cases and 361 controls. Mean age of presentation in cases was 52.06 years (p = .001) with male predominance (69.83%, p = .000011). Active COVID-19 infection at the time of presentation of ROCM (57.54%, p < .0001), moderate to severe COVID-19 (p < .0001), steroid administration (OR 3.63, p < .00001), uncontrolled diabetes (OR 32.83, p < .00001), random blood sugar >178 mg/dl were associated with development of CA-ROCM. Vaccination showed a protective effect (p = .0049). In cases with intracranial or cavernous sinus extension there was history of steroid administration (OR 2.89, p = .024) and orbital apex involvement on imaging (OR 6.202, p = .000037) compared to those with only rhino-orbital disease. CONCLUSION: Male gender, active COVID-19 infection, moderate or severe COVID-19, uncontrolled diabetes, steroid administration during COVID-19 treatment are risk factors for developing rhino-orbital-cerebral mucormycosis. Vaccination is protective. Random blood sugar of >178 mg/dl in COVID-19 positive or recovered patients should warrant close observation and early detection of ROCM. Presence of ophthalmoplegia, blepharoptosis at first clinical presentation and orbital apex involvement on imaging are associated with intracranial extension in ROCM.

Management of Marcus Gunn jaw wink syndrome with tarsofrontalis sling vis a vis levator excision and frontalis sling: a comparative study.

PURPOSE: To compare the results between tarsofrontalis sling (TFS) and levator palpebrae superioris (LPS) excision with TFS in cases of ptosis with Marcus Gunn jaw winking syndrome (MGJWS). METHOD: A retrospective review of records of all patients undergoing either TFS (group A) or LPS excision along with TFS (group B) in cases of ptosis with MGJWS was done over the past 10 years and their results were compared. RESULTS: The study included 73 patients (75 eyes). There were 36 patients (36 eyes) in group A and 37 patients (39 eyes) in group B. There was a significant reduction in the excursion due to MGJWS from 4.7 ± 1.49 to 1.91 ± 1.04 mm in group A (p = .001) and 4.65 ± 1.34 to 1.79 ± 0.98 mm in group B (p < .05). The reduction in excursion due to MGJWS and lagophthalmos were comparable in both groups. The mean follow-up in group A was 5.62 ± 6.94 (Range: 1-24) months and group B was 19.15 ± 29.16 (Range: 1-96) months (p = .01). CONCLUSION: Both TFS and LPS excision with TFS is equally effective in dampening the eyelid excursion in MGJWS. Tarsofrontalis sling is a safe, easy and effective technique for MGJWS with lesser complication.

Sporadic Burkitt Lymphoma Involving the Orbit - A Report of Two Cases and Review of Literature.

Burkitt lymphoma (BL) is an aggressive, rapidly growing B-cell non-Hodgkin lymphoma found predominantly in children and has three clinical subtypes. The sporadic subtype, seen in non-endemic areas, typically presents as an abdominal mass. Primary orbital involvement is rarely reported. We report two cases of sporadic orbital BL manifesting as unilateral rapidly progressive proptosis with orbit being the initial site of presentation. Following an incision biopsy, BL was confirmed on histopathology and immunohistochemistry. Both patients demonstrated a remarkable improvement with systemic chemotherapy. Burkitt lymphomas grow rapidly with the potential for vision loss. Albeit rare, clinicians should be aware of this entity as timely diagnosis and initiation with chemotherapy display a dramatic response.

Intermittent Manual Carotid Compression as a Treatment Option for Indirect Low Flow Carotid Cavernous Fistula.

PURPOSE: To evaluate the efficacy of intermittent manual carotid compression (IMCC) in the management of low-flow carotid cavernous fistulae (CCF). MATERIALS AND METHODS: Patients diagnosed with low-flow CCF and treated with IMCC over a period of 13 years were retrospectively analyzed. Data analyzed included demographic details, clinical features, type of CCF, and response to therapy. Outcomes were categorized as complete cure, partial cure, and no cure or worsening. Patients with complete and partial cure were grouped as good outcome whereas those with no cure or worsening as poor outcome. RESULTS: A total of 44 patients were advised IMCC for low-flow CCF, of whom five were lost to follow-up. Results of the remaining 39 patients were analyzed, of whom 21 (53.8%) were males. The mean age at presentation was 54.38 ± 14.54 years. The median duration between the onset of symptoms and presentation was 5.0 ± 4.10 months. The common presenting features were episcleral congestion and proptosis (89.7%), extraocular motility restriction (66.7%), and diplopia (48.7%). Most common CCF type was type D (34, 87.2%). All patients were advised to undergo IMCC. Good outcome was seen in 35 patients (89.7%, 95% CI: 80.2% to 99.2%), whereas poor outcome was seen in four (10.3%) patients. The mean duration of follow-up was 15.91 ± 21.87 months. CONCLUSION: The present study found a good outcome with IMCC in 89.7% cases of indirect low-flow CCF with no major complications. It should be considered the management of choice in patients who are systemically unfit or cannot afford endovascular embolization.

Radiopathological Correlation in Orbital Lesions.

PURPOSE: The objective is to analyze the radiological diagnosis of orbital lesions and their correlation with the final histopathological findings. We compared the initial reports by extramural radiologists and an in-house radiologist specialized in orbital imaging to evaluate the diagnostic accuracy in the interpretation of orbital imaging. METHODS: This was a retrospective chart review of forty patients referred to a Tertiary Eye Care Center in South India over a period of 7 years. These patients already had their imaging done elsewhere. The imaging was re-evaluated by an in-house radiologist. The radiological findings were correlated with the histopathological diagnosis. The diagnostic accuracy between the two radiologists was compared. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value in differentiating malignant from benign lesions were calculated in both groups. The sensitivity and PPV of the radiological diagnosis for neoplastic and inflammatory lesions in both groups were analyzed. RESULTS: The accuracy in differentiating malignant from benign and inflammatory lesions by our in-house radiologist and extramural radiologists was 95% (κ = 0.9 [0.764, 0.997]) and 50% (κ = 0.036 [-0.160, 0.232]), respectively. The sensitivity and PPV of the radiological diagnosis by our in-house radiologist were 93.31% and 100% for benign lesions and 95.24% and 95.24% for malignant lesions. On the contrary, reports from the extramural radiologists showed a sensitivity and PPV of 76.92% and 66.67% for benign lesions and 14.28% and 60% for malignant lesions. CONCLUSION: A high radiological diagnostic accuracy is possible when analyzed by radiologists experienced in orbital imaging.

Dysthyroid optic neuropathy: Demographics, risk factors, investigations, and management outcomes.

Purpose: To analyze the clinical presentations, risk factors, and management outcomes in patients presenting with dysthyroid optic neuropathy (DON). Methods: This is a retrospective, single-center study carried out on consecutive patients presenting with DON over a period of 4 years (2013-2016). The VISA classification was used at the first visit and subsequent follow-ups. The diagnosis was based on optic nerve function tests and imaging features. Demographic profiles, clinical features, risk factors, and management outcomes were analyzed. Results: Thirty-seven eyes of 26 patients diagnosed with DON were included in the study. A significant male preponderance was noted (20, 76.92%). Twenty patients (76.9%, P = 0.011) had hyperthyroidism, and 15 (57.69%, P = 0.02) were smokers. Decreased visual acuity was noted in 28 eyes (75.6%). Abnormal color vision and relative afferent pupillary defects were seen in 24 (64.86%) eyes, and visual field defects were seen in 30 (81.01%) eyes. The visual evoked potential (VEP) showed a reduced amplitude in 30 (96.77%, P = 0.001) of 31 eyes and delayed latency in 20 (64.51%, P = 0.0289) eyes. Twenty-six (70.27%) patients were treated with intravenous methyl prednisolone (IVMP) alone, whereas 11 (29.72%) needed surgical decompression. The overall best-corrected visual acuity improved by 0.2 l logMARunits. There was no statistically significant difference in outcome between medically and surgically treated groups. Four patients developed recurrent DON, and all of them were diabetics. Conclusion: Male gender, hyperthyroid state, and smoking are risk factors for developing DON. VEP, apical crowding, and optic nerve compression are sensitive indicators for diagnosing DON. Diabetics may have a more defiant course and are prone to develop recurrent DON.

A Case-Control Study to Determine the Microbiological Spectrum and Antibiotic Sensitivity Patterns in Congenital Nasolacrimal Duct Obstruction.

Purpose: To analyze the microbiological spectrum and antibiotic sensitivity patterns in children with congenital nasolacrimal duct obstruction (CNLDO). Methods: One hundred thirty-four eyes of 123 children in the age group of 0-16 years with a diagnosis of CNLDO who underwent lacrimal surgical procedures were included in this prospective comparative study. Sixty-two children in the age-matched group planned for intraocular surgery with patent nasolacrimal duct were deemed controls. The conjunctival swab after performing Regurgitation on Pressure over the Lacrimal Sac in the CNLDO group and the conjunctival swab in controls were sent for microbiological analysis. Antibiotic susceptibility testing was done for commonly employed antibiotics by the Kirby Bauer disk diffusion method. Results: Of 134 samples collected in the CNLDO group, 111 (82.8%) samples were culture positive. There were 165 bacteria isolated, among which 139 (84.24% of isolates) were Gram-positive bacteria, and 26 (15.75% of isolates) were Gram-negative. Fungal isolates were obtained in 2.23% of cases. The most common Gram-positive isolate was Staphylococcus epidermidis (S. epidermidis) (n = 51, 30.9% of total isolates), and the most common Gram-negative isolate was Haemophilus influenza species (n = 9, 5.5% of total isolates). Gram-positive isolates were sensitive mostly to gentamicin and vancomycin (95.5% each), and Gram-negative isolates to amikacin (92.3%). Both Gram-positive and Gram-negative isolates were susceptible to gatifloxacin (80% each). Probing outcomes were similar among Gram-positive (success, 84.6%) and Gram-negative (success, 84.0%) organisms. Conclusions: There was a predominance of Gram-positive isolates in children with CNLDO with S. epidermidis being the most common. The microbiological profile did not have any effect on the outcomes of probing.

EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.

The epidermal growth factor receptor (EGFR) is a prime oncogene that is frequently amplified in glioblastomas. Here we demonstrate a new tumour-suppressive function of EGFR in EGFR-amplified glioblastomas regulated by EGFR ligands. Constitutive EGFR signalling promotes invasion via activation of a TAB1-TAK1-NF-κB-EMP1 pathway, resulting in large tumours and decreased survival in orthotopic models. Ligand-activated EGFR promotes proliferation and surprisingly suppresses invasion by upregulating BIN3, which inhibits a DOCK7-regulated Rho GTPase pathway, resulting in small hyperproliferating non-invasive tumours and improved survival. Data from The Cancer Genome Atlas reveal that in EGFR-amplified glioblastomas, a low level of EGFR ligands confers a worse prognosis, whereas a high level of EGFR ligands confers an improved prognosis. Thus, increased EGFR ligand levels shift the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastomas by suppressing invasion. The tumour-suppressive function of EGFR can be activated therapeutically using tofacitinib, which suppresses invasion by increasing EGFR ligand levels and upregulating BIN3.

Ramal bone graft for management of infra-orbital rim fractures with defects - Technical note and a series of 16 cases.

The purpose is to describe a technique of using ramal bone graft for reconstructing defects of the infra-orbital rim (IOR), assess outcomes and complications. This was a retrospective chart review of 16 patients who underwent ramal bone grafting for IOR fractures. Outcomes evaluated were improvement in clinical findings (lid/globe malposition, tethering of facial skin and implant extrusion) and complications. Data analysis included descriptive statistics. The sample included 15 males and 1 female, with a mean age of 31.6 years. Lid malposition, globe malposition and tethering of facial skin was seen in 16, 13 and 6 patients, respectively. One patient demonstrated extrusion of implant. The mean size of bone harvested was 14 × 7 mm. All patients demonstrated improved globe position post-treatment, while 3 had residual lid retraction. Two patients demonstrated wound dehiscence in the donor site. In conclusion ramal bone graft was found to be a viable alternative for IOR reconstruction.

Does Intraoperative Navigation Improve Implant Position Accuracy in Orbital Fracture Repair?

Purpose: Our aim was to determine if intraoperative navigation (ION) improved radiographic outcomes in patients undergoing delayed primary/secondary orbital reconstruction for inferomedial defects, as measured by volume restoration, enophthalmos correction, and positional accuracy of implants. Patients and Methods: A prospective quasiexperimental study was performed to compare two groups of patients requiring orbital reconstruction. Use of ION was the exposure evaluated. Outcome measures were (i) intraorbital volume and enophthalmos evaluated radiologically, (ii) implant position accuracy, and (iii) procedural duration. Data were analyzed statistically to compare variance between groups. Results: Forty patients (6 females and 34 males) were recruited into the study with a mean age of 27.3 years. The study group demonstrated a greater reduction of intraorbital volume (0.49 cu.cm; p = 0.02) and enophthalmos (0.72 mm; p = 0.001). Implant positioning was more accurate using ION, with less mediolateral (p = 0.006) and yaw (p = 0.04) deviations. Surgical time for implant positioning was shorter by 17 min, with navigation (p < 0.001). Conclusion: The use of ION demonstrated radiographic improvements in volume restoration, enophthalmos correction, as well as accuracy of implant positioning, in patients requiring delayed primary/secondary orbital reconstruction.

Classification and Management of Infra-orbital Rim Fractures.

PURPOSE: Fractures of the infraorbital rim (IOR) are often undertreated with a resultant compromise of facial esthetics and function. The purpose of this research was to identify types of IOR fractures related clinical findings and assess post-treatment outcomes. METHODS: A retrospective cohort study was implemented involving all patients treated for IOR fractures during an 18-month period. Data consisted of treatment records, pretreatment and post-treatment photographs, and computed tomographic (CT) scans. The types of fractures were matched to the treatment instituted. The type of fracture was the independent variable, while the dependent variables were (i) clinical findings such as lid and globe malposition, tethering of facial skin, diplopia, and infraorbital nerve paresthesia, and (ii) treatment outcome assessed by surgeon and patient. Data were analyzed statistically to study frequencies, proportions, and associations using SPSS (v26, IBM, Armonk, NY). RESULTS: Forty-three patients (41 males and 2 females) with IOR fractures were treated between July 2019 and January 2021. The age range was 18 to 50 years. The etiology for trauma in all patients was a motor vehicle accident. Fifty-one fractures were classified into 6 types based on CT presentation. The single line fracture (concomitant with other bones) was the most prevalent (58.8%), while globe malposition was the most common clinical finding (35.8%). Lid malposition, globe malposition, and tethering of facial skin were associated with the type of IOR fracture (P = .04, P = .02, and P = .01, respectively). Excellent outcomes were scored in 32 and 25 fractures by the surgeon and patients, respectively, (P = .015 and P = .003). The inter-rater agreement between the surgeon and patient was significant (Kappa = 0.680; P < .001). CONCLUSIONS: Clinical findings in IOR fractures are dependent on the fracture type. Treatment of fractures based on their CT presentation produces effective management of signs/symptoms and improved treatment outcomes.

Orbital abscess: 20 years' experience at a tertiary eye care center.

PURPOSE: To study the clinical, microbiological profile and management outcomes of orbital abscess at a tertiary care center in South India. MATERIAL AND METHOD: In a retrospective interventional case series, we reviewed all patients diagnosed with orbital cellulitis from 2000-2020. The data analyzed included demographic profile, clinical and radiological features, microbiological profile, and management outcome. RESULTS: A total of 921 cases of orbital and periorbital infections were reviewed. Seventy-two cases were diagnosed as orbital cellulitis. Thirty-four cases (47.22%) had radiological evidence of orbital abscess. The median age was 20.63 years. Three patients (8.82%) were neonates. A male preponderance was noted (23, 67.65%). Sinusitis (10, 29.41%) and diabetes (5, 14.7%), were the most common predisposing factors. Optic neuropathy was seen in 15 (44.11%) patients, cavernous sinus thrombosis in two patients (5.88%), and septicemia in one patient (2.94%) Multiple orbital abscesses were noted in 7 (20.59%) cases. All patients underwent surgical drainage. Methicillin-sensitive Staphylococcus aureus was the most common organism isolated in 14 patients (41.18%). Vision improvement or stabilization was seen in all except 3 (8.82%). CONCLUSION: Orbital abscess is a potential sight-threatening orbital infection. The infective process can spread and ascend up to involve cavernous sinus thereby becoming life-threatening. A timely diagnosis and intervention can halt the disease process and help restore vision in many cases.

Post-traumatic orbital sub periosteal hematoma in children: Clinical spectrum and management outcomes.

Orbital subperiosteal hematoma (OSPH) is a rare entity following blunt trauma that can significantly affect the vision of a growing child. The purpose of this study was to describe the spectrum of the clinical presentations along with the imaging findings and treatment outcome of traumatic OSPH. This is a retrospective case series of six patients below 16 years of age, diagnosed with OSPH following trauma. Electronic medical records were reviewed for details of clinical features, imaging findings, management details and outcomes. The median duration of the presentation was 7 days (range 6-50 days). Proptosis and dystopia remained the most common presenting features. Significant vision loss was noted in four patients at presentation. A computed tomography (CT) scan revealed the superior quadrant of the orbit to be involved most frequently. Five patients were treated surgically and one conservatively. Significant vision loss was noted in one patient despite of initial surgical management. Although rare, OSPH should be considered a differential diagnosis in children presenting with proptosis and dystopia following blunt trauma. Younger children are particularly at higher risk for developing permanent visual loss and should be treated promptly by draining the OSPH.