Bilateral Dilated Superior Ophthalmic Veins in a Patient With an Arteriovenous Dialysis Fistula.

A 64-year-old man presented with 4 months of diplopia. He had end-stage renal disease requiring a cephalic transposition brachiocephalic fistula that was no longer in use following successful renal transplantation. On presentation, he had bilateral proptosis, extraocular movement restriction, chemosis, tortuous episcleral vessels, and caruncular injection. Non-contrast CT of the orbits demonstrated dilation of both superior ophthalmic veins, and CT angiography showed asymmetric enlargement of both cavernous sinuses and superior ophthalmic veins. A carotid-cavernous fistula was suspected, but cerebral angiography revealed shunting from the old fistula with intracranial drainage and cerebral venous hypertension. Aberrant retrograde drainage resulted from anatomical compression of the left brachiocephalic vein. The fistula was ligated, and at 1-week follow-up, the patient had marked improvement in extraocular movements and orbital congestion with near complete resolution of diplopia. Postoperative CT angiography obtained 2 months later demonstrated decreased size of both superior ophthalmic veins, consistent with improvement of venous hypertension.

Artificial Intelligence Automation of Proptosis Measurement: An Indicator for Pediatric Orbital Abscess Surgery.

INTRODUCTION: To evaluate the ability of artificial intelligence (AI) software to quantify proptosis for identifying patients who need surgical drainage. METHODS: We pursued a retrospective study including 56 subjects with a clinical diagnosis of subperiosteal orbital abscess (SPOA) secondary to sinusitis at a tertiary pediatric hospital from 2002 to 2016. AI computer software was developed to perform 3D visualization and quantitative assessment of proptosis from computed tomography (CT) images acquired at the time of hospital admission. The AI software automatically computed linear and volume metrics of proptosis to provide more practice-consistent and informative measures. Two experienced physicians independently measured proptosis using the interzygomatic line method on axial CT images. The AI software and physician proptosis assessments were evaluated for association with eventual treatment procedures as standalone markers and in combination with the standard predictors. RESULTS: To treat the SPOA, 31 of 56 (55%) children underwent surgical intervention, including 18 early surgeries (performed within 24 h of admission), and 25 (45%) were managed medically. The physician measurements of proptosis were strongly correlated (Spearman r = 0.89, 95% CI 0.82-0.93) with 95% limits of agreement of ± 1.8 mm. The AI linear measurement was on average 1.2 mm larger (p = 0.007) and only moderately correlated with the average physicians' measurements (r = 0.53, 95% CI 0.31-0.69). Increased proptosis of both AI volumetric and linear measurements were moderately predictive of surgery (AUCs of 0.79, 95% CI 0.68-0.91, and 0.78, 95% CI 0.65-0.90, respectively) with the average physician measurement being poorly to fairly predictive (AUC of 0.70, 95% CI 0.56-0.84). The AI proptosis measures were also significantly greater in the early as compared to the late surgery groups (p = 0.02, and p = 0.04, respectively). The surgical and medical groups showed a substantial difference in the abscess volume (p < 0.001). CONCLUSION: AI proptosis measures significantly differed from physician assessments and showed a good overall ability to predict the eventual treatment. The volumetric AI proptosis measurement significantly improved the ability to predict the likelihood of surgery compared to abscess volume alone. Further studies are needed to better characterize and incorporate the AI proptosis measurements for assisting in clinical decision-making.

Utility of diffusion-weighted imaging to differentiate benign and malignant solid orbital tumours.

OBJECTIVE: We assessed the utility of apparent diffusion coefficients (ADCs) derived from diffusion-weighted imaging to differentiate benign and malignant orbital tumours by oculoplastic surgeons in the clinical setting and sought to validate observed ADC cut-off values. DESIGN AND PARTICIPANTS: Retrospective review of patients with benign or malignant biopsy-confirmed orbital tumours. METHODS: Blinded graders including 2 oculoplastic surgeons, 1 neuroradiologist, and 1 medical student located and measured orbital tumour ADCs (10-6 mm2/s) using the Region of Interest tool. OUTCOME MEASURES: Nonradiologist measurements were compared with each other to assess reliability and with an expert neuroradiologist measurement and final pathology to assess accuracy. RESULTS: Twenty-nine orbital tumours met inclusion criteria, consisting of 6 benign tumours and 23 malignant tumours. Mean ADC values for benign orbital tumours were 1430.59 ± 254.81 and 798.68 ± 309.12 mm2/s for malignant tumours. Our calculated optimized ADC cut-off to differentiate benign from malignant orbital tumours was 1120.84 × 10-6 mm2/s (sensitivity 1, specificity 0.9). Inter-rater reliability was excellent (intraclass correlation coefficient = 0.92; 95% CI, 0.86-0.96). Our 3 graders had a combined accuracy of 84.5% (92.3%, 92.3%, and 65.4%). CONCLUSIONS: Our ADC cut-off of 1120.84 × 10-6 mm2/s for benign and malignant orbital tumours agrees with previously established values in literature. Without priming with instructions, training, or access to patient characteristics, most tumours were correctly classified using rapid ADC measurements. Surgeons without radiologic expertise can use the ADC tool to quickly risk stratify orbital tumours during clinic visits to guide patient expectations and further work-up.

Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization.

In-situ hybridization provides a convenient and reliable method to detect human papillomavirus (HPV) infection in formalin-fixed paraffin-embedded tissue. Cases of conjunctival papillomas, conjunctival intraepithelial neoplasia (CIN), conjunctival carcinoma in situ (cCIS), and invasive squamous cell carcinoma (SCC), in which low-risk (LR) and/or high-risk (HR) HPV types were evaluated by RNA or DNA in-situ hybridization, were retrospectively identified. LR HPV types were frequently detected in conjunctival papillomas (25/30, 83%), including 17/18 (94%) with RNA probes, compared to 8/12 (75%) with DNA probes. None of the CIN/cCIS or SCC cases were positive for LR HPV by either method. HR HPV was detected by RNA in-situ hybridization in 1/16 (6%) of CIN/cCIS cases and 2/4 (50%) of SCC cases, while DNA in-situ hybridization failed to detect HPV infection in any of the CIN/cCIS lesions. Reactive atypia and dysplasia observed in papillomas was generally associated with the detection of LR HPV types. Collectively, our findings indicate RNA in-situ hybridization may provide a high-sensitivity approach for identifying HPV infection in squamous lesions of the conjunctiva and facilitate the distinction between reactive atypia and true dysplasia. There was no clear association between HPV infection and atopy in papillomas or dysplastic lesions.

Clinicopathological Features of 19 Eyelid Pilomatrixomas.

Introduction: Pilomatrixoma is a relatively rare, benign tumor arising from the hair root matrix. It is found frequently on the head and neck, with most involving the eyebrow in the periocular region. In contrast, eyelid pilomatrixoma is less common, and often clinically misdiagnosed. Here, we present clinical and histological data from 19 pilomatrixomas arising in the eyelid. Methods: The study represents a retrospective study of eyelid pilomatrixoma diagnosed at our institution since 1981. All slides were reviewed, and demographic as well as clinical data were obtained. Results: Patient ages ranged from 2 to 63 years (mean 24 years), including 12 (63%) females and 7 (37%) males. Eight (42%) and 4 (21%) cases arose in the first and second decades of life, respectively. Upper eyelid involvement was found in 14 (74%) of cases. Microscopically, the tumors were characterized by basaloid and shadow cells accompanied by calcification and foreign body giant cells. Conclusions: Eyelid pilomatrixoma is rarely suspected clinically, and can be mistaken for cyst, chalazion, sebaceous carcinoma, and other tumors. Physicians should consider the possibility of pilomatrixoma in the eyelid area, especially in children or young female patients. Complete excision is curative, and diagnosis can generally be established by histopathological examination.

Use of computer-assisted surgery in the orbit.

PURPOSE: To present the application of computer-assisted surgery (CAS) in pre-operative planning, intra-operative navigation, and post-operative assessment as an adjunct tool in orbital surgery. METHODS: An IRB-approved, retrospective review was performed to identify patients who had undergone orbital surgery by a single surgeon from July 2013 to December 2019 with attention to pre-operative virtual surgical planning, intra-operative navigation, and post-operative assessment. The reasons and methods of CAS use were classified. RESULTS: The use of computer-assisted technologies was identified in 91 cases out of 464 orbital surgeries (19.6%). This included 23 (25.3%) orbital decompression surgeries, 39 (42.9%) fracture repairs, and 25 (27.5%) orbital tumors. In all cases, pre-, intra-, and post-operative CAS allowed for increased operative efficiency and safety with good outcomes. CONCLUSIONS: Use of CAS in orbital surgery can allow for complex radiographic analysis and in select cases is a great tool to add to the orbital surgeon's armamentarium.

Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring.

PURPOSE: To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS: Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS: An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS: Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas.

Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.

High-risk human papillomavirus and ZEB1 in ocular adnexal sebaceous carcinoma.

BACKGROUND: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy. Oncologic drivers of ocular sebaceous carcinoma are incompletely understood. METHODS: A retrospective search of our pathology archives for OA sebaceous carcinoma identified 18 primary resection specimens. Immunohistochemistry for p16 and ZEB1 and RNA in situ hybridization for high-risk human papillomavirus (HPV) subtypes were performed. RESULTS: High-risk HPV was demonstrated in 2/11 (18%) cases. p16 overexpression was observed in 10/11 (91%). No association between gender, age at presentation, tumor location, intraepithelial spread, tumor size, and T stage was observed between HPV-driven and nonviral cases. High expression of ZEB1 was observed in the intraepithelial component of 4/14 (28%) cases and in the subepithelial component of 1/13 (7%) cases. ZEB1 overexpression was not associated with HPV status, T stage, or tumor size. CONCLUSION: As previously described by others, our findings suggest that a subset of OA sebaceous carcinomas may arise via an HPV-dependent pathway. However, unlike high-risk HPV-driven carcinomas of the oropharynx, we did not identify an association between HPV-status and prognostic features. Furthermore, p16 expression was not a useful surrogate marker for HPV-driven disease. ZEB1 overexpression is not associated with HPV in our cohort of ocular sebaceous carcinoma.

Compound Coherent Plane-Wave Ultrasound Imaging of Vascular Malformations of the Orbit.

PURPOSE: Prior color-flow Doppler ultrasound studies of the eye have been performed with systems that exceed US Food and Drug Administration permissible ophthalmic ultrasonic energy limits. The authors report a study of orbital vascular malformations using a novel, Food and Drug Administration compliant, ultrafast compound coherent plane-wave ultrasound device to produce power Doppler images. METHODS: Using a Verasonics Vantage 128 ultrasound engine and a user-developed MATLAB program with a 5-MHz linear-array probe, compound coherent plane-wave ultrasound data were collected on patients with orbital vascular malformations. Real-time color-flow Doppler visualized orbital blood flow. Power Doppler images were produced by post-processing compound coherent plane-wave ultrasound data acquired continuously for 2 seconds. RESULTS: Compound coherent plane-wave ultrasound was performed on 3 orbital vascular malformations (1 venolymphatic malformation, 1 infantile hemangioma, and 1 arteriovenous malformation). Compound coherent plane-wave ultrasound produced a high-resolution depiction of orbital blood flow for orbital vascular malformations with high sensitivity to slow flow. CONCLUSIONS: Analysis of blood flow within orbital lesions informs treatment planning. Compound coherent plane-wave ultrasound is an emerging ultrasound modality that falls within the Food and Drug Administration guidelines for use in the orbit and provides information to characterize orbital vascular malformations.

High-risk human papillomavirus positive primary squamous cell carcinoma of the lacrimal gland: a case report.

A 78-year-old Caucasian female presented with a painless mass in the right orbit that had progressively enlarged over several months. Computed tomography scan of the orbits showed a right lacrimal gland mass with no bony erosion. Histopathologic analysis of the biopsy specimen revealed invasive squamous cell carcinoma positive via in-situ hybridization for high-risk human papillomavirus. The patient underwent successful removal of the right lacrimal gland tumor en bloc, followed by adjuvant radiotherapy. This is an extremely rare case of primary squamous cell carcinoma of the lacrimal gland and the first report describing human papillomavirus positivity in this tumor location.

Chocolate Cysts Associated With Porous Polyethylene Orbital Implants.

Late-onset orbital hemorrhage is a rare complication of alloplastic implant use in orbital wall reconstruction following trauma. The authors report 3 patients with chocolate cysts presenting 3 to 9 years after orbital fracture repair with porous polyethylene implants. All patients were managed by implant removal and evacuation of cyst contents. Complete excision of the cyst was performed in 1 patient, while partial excision of the capsule was performed in 2 patients. Improvement of symptoms associated with the mass effects of the cyst was noted after surgical intervention. The authors also report the first case of orbital volume expansion from a chocolate cyst associated with a nonbarriered porous polyethylene implant. Delayed hemorrhage with capsule formation, although extremely rare, is a possible complication following orbital fracture repair with porous polyethylene implants.

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Doxycycline Injection for Sclerotherapy of Lower Eyelid Festoons and Malar Edema: Preliminary Results.

PURPOSE: To investigate the safety and efficacy of direct, intralesional doxycycline hyclate injection for improving the appearance of cosmetically significant lower eyelid festoons and malar edema. METHODS: An Institutional Review Board approved, retrospective review was performed of 15 consecutive patients with malar edema and/or festoons injected with doxycycline hyclate at a concentration of 10 mg/ml. Pre- and postinjection photographs were reviewed and graded on a scale of 0 to 3 (0: no festoon; 1: small festoon; 2: medium festoon; 3: large festoon) by 2 masked physician observers. Patients were excluded from the final analysis if they received an alternate dose concentration, had incomplete photographic records, or did not follow up. Student t test was used for statistical analysis. RESULTS: Twenty consecutive treatment areas of 11 patients were included in the analysis. Final follow up ranged from 3 to 104 weeks, with a mean follow up of 22.5 weeks. The average (standard deviation) initial festoon grade of 2.5 (0.58) decreased to 0.9 (0.82) with a p value of <0.001. The average number of injections performed per side was 1.4 (range: 1-2). The mean volume per injection was 0.72 ml (range: 0.15-2.0 ml). Commonly documented subjective complaints were burning sensation with injection, pain, bruising, and erythema. There were no other dermatologic or visual complications following treatment. CONCLUSIONS: These preliminary results suggest that intralesional injections of doxycycline hyclate at a concentration of 10 mg/ml may be an effective treatment option for cosmetically significant lower eyelid festoons and malar edema. Future prospective studies with increased patient numbers, increasing concentrations, combination therapies with local anesthetic or regional nerve blocks, and longer follow up are needed to validate these results and determine optimal injection technique.

Predominant Contribution of Superior Rectus-Levator Complex Enlargement to Optic Neuropathy and Inferior Visual Field Defects in Thyroid Eye Disease.

PURPOSE: To compare extraocular muscle volumes in thyroid eye disease patients with and without compressive optic neuropathy. METHODS: A retrospective review of 44 orbital CT scans (28 orbits without compressive disease and 16 orbits with compressive optic neuropathy) was conducted. The extraocular muscle volumes, summated soft tissue volumes, and optic nerve volumes were calculated at a section in the posterior 1/3 of the orbit. The visual fields of the orbits with compressive optic neuropathy were analyzed. RESULTS: The mean combined extraocular muscle/summated soft tissue volume ratio and the mean superior rectus-levator complex/summated soft tissue volume ratio were greater in those with compressive optic neuropathy than in those without compressive optic neuropathy (p = 0.02, 0.008, respectively). The ratio of the mean inferior, medial, or lateral rectus/summated soft tissue volume did not differ significantly between patients with or without compressive optic neuropathy (p values of 0.315, 0.615, and 0.254, respectively). Visual field analysis of the compressive optic neuropathy group demonstrated that 58% of the orbits with visual field defects had inferior field defects. CONCLUSIONS: When measured at a section near the orbital apex, the mean combined muscle/summated soft tissue volume ratio and the mean superior rectus-levator complex/summated soft tissue volume ratio are greater in those with compressive disease than those without. This suggests that the specific enlargement of the superior rectus-levator complex makes a significant contribution to thyroid eye disease-compressive optic neuropathy and may explain the inferior visual field deficits classically found in this group of patients.

Age-Related Changes in the Clinical Phenotype of Compressive Optic Neuropathy in Thyroid Eye Disease.

PURPOSE: This study compares the age-related clinical features of thyroid eye disease-compressive optic neuropathy (TED-CON) to those with noncompressive disease (TED-NC). METHODS: A retrospective case series review of 165 orbits from 121 patients with TED-CON were compared with an age- and gender-matched cohort of 88 orbits from 44 patients with TED-NC with institutional review board approval. Clinical features including exophthalmos, dyschromatopsia, restricted ocular motility, visual acuity, and mean deviation on 24-2 Humphrey Visual Field were compared in 5 age groups. A previously validated formula, the Columbia TED-CON Diagnostic formula, used to mathematically predict the presence or absence of compressive optic neuropathy was applied, and the sensitivity and specificity of the formula was measured in each age group. RESULTS: Exophthalmos, dyschromatopsia, restricted ocular motility, and mean deviation on 24-2 Humphrey Visual Field vary significantly across age groups in patients with TED-CON. Conversely, only visual acuity and dyschromatopsia vary significantly across age groups in patients with TED-NC. There was a significant difference between the TED-CON and the TED-NC groups when comparing the 2 groups by decade. The Columbia TED-CON Diagnostic formula had high sensitivity and specificity (74-90%) in all age groups. CONCLUSIONS: This is the first study to date demonstrating the age-related variability of clinical characteristics in a large series of patients with either TED-CON or TED-NC. The clinical phenotype of TED-CON varies significantly by decade when examining exophthalmos, dyschromatopsia, ocular motility restriction, and mean deviation on 24-2 Humphrey Visual Field. These clinical characteristics are also significantly different when compared with a population of patients with TED-NC.

Pituitary Adenoma Apoplexy of the Orbit, Diagnosis, and Management With Presurgical Embolization.

Orbital invasion of pituitary adenomas has been previously reported. In this report, the authors describe a 71-year-old female with a prolactinoma that presented with invasion of and apoplexy within the orbit. The patient underwent exenteration, followed by rapid tumor recurrence and growth. Given the hemorrhagic nature of the tumor, she subsequently underwent preoperative embolization and surgical resection. This case is notable in that it illustrates both apoplexy of a pituitary tumor within the orbit and the benefit of presurgical embolization.