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Ocular adnexal sebaceous carcinoma (SebCA) represents one of the most clinically problematic periocular tumors, often requiring aggressive surgical resection. The pathobiology of this tumor remains poorly understood, and few models exist that are suitable for preclinical testing. The aim of this study was to establish new cell lines to serve as models for pathobiological and drug testing. With patient consent, freshly resected tumor tissue was cultured using conditional reprogramming cell conditions. Standard techniques were used to characterize the cell lines in terms of overall growth, clonogenicity, apoptosis, and differentiation in vitro. Additional analyses including Western blotting, short tandem repeat (STR) profiling, and next-generation sequencing (NGS) were performed. Drug screening using mitomycin-C (MMC), 5-fluorouricil (5-FU), and 6-Diazo-5-oxo-L-norleucine (DON) were performed. JHH-SebCA01, JHH-SebCA02, and JHH-SebCA03 cell lines were established from two women and one man undergoing surgical resection of eyelid tumors. At passage 15, they each showed a doubling time of two to three days, and all could form colonies in anchorage-dependent conditions, but not in soft agar. The cells contained cytoplasmic vacuoles consistent with sebaceous differentiation, and adipophilin protein was present in all three lines. STR profiling confirmed that all lines were derived from their respective patients. NGS of the primary tumors and their matched cell lines identified numerous shared mutations, including alterations similar to those previously described in SebCA. Treatment with MMC or 5-FU resulted in dose-dependent growth inhibition and the induction of both apoptosis and differentiation. MYC protein was abundant in all three lines, and the glutamine metabolism inhibitor DON, previously shown to target high MYC tumors, slowed the growth of all our SebCA models. Ocular adnexal SebCA cell lines can be established using conditional reprogramming cell conditions, and our three new models are useful for testing therapies and interrogating the functional role of MYC and other possible molecular drivers. Current topical chemotherapies promote both apoptosis and differentiation in SebCA cells, and these tumors appear sensitive to inhibition or MYC-associated metabolic changes. [ABSTRACT FROM AUTHOR]

Purpose: To compare the accuracy and readability of responses to oculoplastics patient questions provided by Google and ChatGPT. Additionally, to assess the ability of ChatGPT to create customized patient education materials. Methods: We executed a Google search to identify the 3 most frequently asked patient questions (FAQs) related to 10 oculoplastics conditions. FAQs were entered into both the Google search engine and the ChatGPT tool and responses were recorded. Responses were graded for readability using five validated readability indices and for accuracy by six oculoplastics surgeons. ChatGPT was instructed to create patient education materials at various reading levels for 8 oculoplastics procedures. The accuracy and readability of ChatGPT-generated procedural explanations were assessed. Results: ChatGPT responses to patient FAQs were written at a significantly higher average grade level than Google responses (grade 15.6 vs 10.0, p < 0.001). ChatGPT responses (93% accuracy) were significantly more accurate (p < 0.001) than Google responses (78% accuracy) and were preferred by expert panelists (79%). ChatGPT accurately explained oculoplastics procedures at an above average reading level. When instructed to rewrite patient education materials at a lower reading level, grade level was reduced by approximately 4 (15.7 vs 11.7, respectively, p < 0.001) without sacrificing accuracy. Conclusion: ChatGPT has the potential to provide patients with accurate information regarding their oculoplastics conditions. ChatGPT may also be utilized by oculoplastic surgeons as an accurate tool to provide customizable patient education for patients with varying health literacy. A better understanding of oculoplastics conditions and procedures amongst patients can lead to informed eye care decisions. [ABSTRACT FROM AUTHOR]

The authors explain the National Confidential Enquiry into Patient Outcome and Death report and highlight the areas where healthcare managers can help clinicians facilitate the transition of children and young people with chronic health conditions into adult health services. [ABSTRACT FROM AUTHOR]

The National Confidential Enquiry into Patient Outcome and Death reviewed the barriers and facilitators in the process of the transition of children and young people with chronic health conditions into adult health services. The report focuses on five issues – developmentally appropriate healthcare, the involvement of children and young people and their parents or carers in transition planning, communication and coordination of care, the organisation of transition services and leadership – and makes recommendations for practice. [ABSTRACT FROM AUTHOR]

The National Confidential Enquiry into Patient Outcome and Death reviewed the quality of care provided to adults who presented to hospital following an epileptic seizure. Clinical and organisational changes are highlighted that aim to improve patient care and outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To describe tumor response and cranial nerve function outcomes after administration of anti-PD-1 to patients with cutaneous squamous cell carcinoma (CSCC) with perineural spread to cranial nerves (CN) extending into the cavernous sinus. Methods: Electronic patient records from a single institution were queried for patients with CSCC of the head and neck causing diplopia (ICD-10 H53.2) who were treated with anti-PD-1. Data extracted included demographics, duration of anti-PD-1 therapy, immune-mediated adverse reactions, tumor response per adapted RECIST v1.1, and changes in CN function and symptoms (e.g., pain). All patients were prescribed cemiplimab 350 mg IV q3 weeks. Results: Four patients met inclusion criteria. They had varying degrees of pain and sensory deficits in branches of the trigeminal nerve (CN V). One, 2, 3 and 1 patients had baseline involvement of CN III, IV, VI and VII, respectively. MRI confirmed perineural cavernous sinus involvement in all patients. Duration of anti-PD-1 therapy ranged 15–60 weeks. All patients experienced an objective anti-tumor response to anti-PD-1; partial response n = 2, complete response n = 2. At a median follow-up of 22 months, responses were ongoing in all patients. All patients demonstrated improvement in ocular motility deficits and pain with resolution of symptoms in 3 and 1 patients, respectively. Conclusion: Administration of anti-PD-1 to patients with CSCC with perineural spread into the cavernous sinus can generate durable anti-tumor regressions and restore CN function, while sparing the morbidity associated with surgical resection and/or radiotherapy. Our findings add to emerging literature supporting this treatment approach for this patient population. [ABSTRACT FROM AUTHOR]

Background/aims To assess surgical patterns in ophthalmology by subspecialty in the USA. Methods Ophthalmic surgeons were categorised as comprehensive/subspecialist based on billed procedures in the 2017-2018 Medicare Provider Utilization and Payment Data. Poisson regression models assessed factors associated with physicians performing surgeries in the core domain (eg, cataract extractions) and subspecialty domain. Models were adjusted for provider gender, time since graduation, geographical region, practice setting and hospital affiliation. Results There were 10 346 ophthalmic surgeons, 74.7% comprehensive and 25.3% subspecialists. Cataract extractions were performed by 6.0%, 9.9%, 21.0%, 88.1% and 95.3% of specialists in surgical retina, neuro-ophthalmology/ paediatrics, oculoplastics, glaucoma and cornea, respectively. Retina specialists were more likely to perform cataract surgery if they were 20-30 or>30 years in practice (relative risk: 2.20 (95% CI: 1.17 to 4.12) and 3.74 (95% CI: 1.80 to 7.76), respectively) or in a non-metropolitan setting (3.78 (95% CI: 1.71 to 8.38)). Among oculoplastics specialists, male surgeons (2.71 (95% CI: 1.36 to 5.42)), those in practice 10-20 years or 20-30 years (1.93 (95% CI: 1.15 to 3.26) and 1.91 (95% CI: 1.11 to 3.27), respectively) and in non-metropolitan settings (3.07 (95% CI: 1.88 to 5.02)) were more likely to perform cataract surgery. Only 26 of the 2620 subspecialists performed surgeries in two or more subspecialty domains. Conclusions There is a trend towards surgical subspecialisation in ophthalmology in the USA whereby some surgeons focus their surgical practice on subspecialty procedures and rarely perform surgeries in the core domain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Ocular amyloidoma is a rare disorder characterized by deposition of insoluble proteinaceous fibrils in the extracellular space of the ocular adnexa. This study details the clinicopathologic features and proteomic characteristics of periocular amyloid deposition.Methods: Specimens (1991-2020) were retrieved and reviewed. All available H&E slides and special stains were reviewed. Proteomic analysis was performed using immunohistochemistry (IHC) for IgG, IgG4, IgA, IgD, IgM, CD20, CD3, CD138, and κ/λ, as well as chromatography-electrospray tandem mass spectrometry on formalin-fixed, paraffin-embedded tissue.Results: There were 14 patients (7 men, 7 women). The depositions involved eyelid (n = 3), conjunctiva (n = 8), and orbit (n = 3). All patients were adults with a median age at diagnosis of 56 (range, 39-88) years. The deposits were predominantly λ light chain restricted (n = 6) and mixed light chains (n = 2), and one case was κ predominant. Two of the cases with a mixture of κ and λ light chains had an excess of transthyretin by mass spectrometry. Four of the cases did not have adequate material for proteomic subtyping.Conclusions: Amyloidomas involving ocular adnexa contain a variety of amyloid-related and immunoglobulin-associated peptides. The λ light chain predominates as in other body sites, but mixed patterns and rarely κ light chain restriction may be encountered. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Interviews with Jacqui Fifer and Tom Cronin, makers of The Portal. [ABSTRACT FROM AUTHOR]

Purpose of review: In this review, we review the current understanding of the pathogenesis and known associations in thyroid eye disease. We describe recent developments in treatment paradigms including recently approved agents, upcoming future therapies, and current technologies and strategies in approaching patients surgically. Recent findings: The development of biologic agents, such as rituximab, tocilizumab, and most recently the human monoclonal antibody teprotumumab that binds to the IFG-1 receptor, has altered the management of patients in the active phase of thyroid eye disease. Randomized controlled trials have demonstrated teprotumumab infusion in the relatively early phase of orbital inflammation results in a durable reduction in proptosis and strabismus in the majority of patients. Regarding surgical management, many studies have described refining surgical techniques and approaches, with specific attention to customizing approaches based on pre-operative assessments and using computer-assisted technologies. Summary: New insights in gene expression have improved our understanding of the etiology of thyroid eye disease and helped to define the role of lifestyle modifications. Steroids continue to have a role in temporizing severe orbitopathy while teprotumumab is useful in patients with moderate disease activity when utilized within 9 months of disease onset. Advances/progress in surgical management continue to increase effectiveness and safety through an ideal, predictable, consistent approach remains elusive. [ABSTRACT FROM AUTHOR]

Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the frequency of primary versus secondary eye removal, frequency of enucleation versus evisceration, and characteristics and outcomes of patients undergoing these procedures after presenting with severe ocular trauma. Patients and Methods: Retrospective chart review of patients presenting to the emergency department (ED) with severe eye trauma necessitating enucleation or evisceration between 2010 and 2018. Results: There were 92 eyes from 90 patients included in our study. Twenty-seven percent of eyes underwent primary removal (n=25, 14 enucleation, 11 evisceration), while 73% of eyes underwent secondary removal (n=67, 50 enucleation, 17 evisceration). The mean patient age was 45.2 years (range 4.2– 92.6); primary enucleation/evisceration patients were older on average than secondary eye removal patients [53.8 years (range 15.9– 91.2) versus 42.2 years (range 4.2– 91.6 years), p=0.04]. A median of 34 days passed between ED presentation and secondary enucleation/evisceration. Before undergoing secondary enucleation/evisceration, patients underwent a median of one ocular procedure (range 0– 14) for various complications of trauma including orbital infection, choroidal or retinal tear or detachment, and wound dehiscence. Open globe injury repairs comprised 43 of the 92 total procedures (47%) performed prior to secondary enucleation/evisceration. Secondary enucleations/eviscerations required a median of seven clinic visits compared to two clinic visits required after primary surgeries (p< 0.01). 10.7% of all patients (n=10) had at least one implant-related complication following enucleation/evisceration, with all but one of these patients being in the secondary enucleation/evisceration group. Conclusion: Primary enucleation or evisceration was performed in 27% of all eye removals, and enucleation was performed in 69.6% of all eye removals. Future research is warranted to determine if primary eye removal may be appropriate and when to consider enucleation versus evisceration. [ABSTRACT FROM AUTHOR]

Assessing the quality of care for patients receiving long-term ventilation is complex given the diversity of this population (0–24 years in this case) and their differing requirements for treatment. This article details how and why such reviews are necessary. [ABSTRACT FROM AUTHOR]

Background: Ehlers‒Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients. Methods: Patients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists. Results: Of 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%‐refractive, 33%‐lens/cataract, 33%‐retina, 59%‐strabismus, 23%‐ oculoplastics, 0%‐cornea, and 25%‐glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis. Conclusions: Patients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery. [ABSTRACT FROM AUTHOR]

Purpose: The Kaneka Lacriflow CL (Lacriflow) bicanalicular lacrimal intubation system was evaluated as a self-retaining alternative to traditional modalities for stenting and dilation of the lacrimal drainage system in proximal lacrimal drainage system stenosis. Patients and Methods: A retrospective chart review was conducted to assess the use of the Lacriflow system for treatment of patients with punctal and canalicular stenosis. Anesthesia type, operative time, and complications were assessed. Results: In the time period evaluated, a total of 72 Lacriflow stents were placed in 45 patients, most commonly under intravenous sedation. Stents were left in place for a mean of 145 days, with 9 stents left in place for more than 1 year, and a mean follow-up time of 263 days. Early complications within 90 days included prolapse in 1 stent, symptomatic colonization for 2 stents, and corneal abrasion in 1 stent in a patient with anterior basement membrane dystrophy. Five additional stents developed colonization in the late postoperative period (four of which were more than 1 year after stent placement). The overall complication rate (per stent) at 3 months after surgery was 5.6% and at all follow-up time points was 13.9%. Operative times were significantly shorter for a cohort of patients undergoing bicanalicular intubation with the Ritleng system (P = 0.015). Conclusion: The Lacriflow bicanalicular stent can be easily placed without general anesthesia. Complication rates are comparable to other bicanalicular intubation systems, but increase with longer time that stents are left in place. [ABSTRACT FROM AUTHOR]

Background: Floppy eyelid syndrome is a disorder in which the tarsal plate is easily distensible and is currently treated with conservative or surgical measures. Human tarsal plate contains type I collagen, which is crosslinked in corneal tissue as a treatment for keratoconus. We hypothesized that collagen crosslinking would similarly stiffen tarsal plate tissue and investigated this in porcine and human tarsal plate specimens.Methods: Riboflavin-sensitized porcine and human tarsus samples were irradiated with ultraviolet-A light. Porcine experiments were analyzed with gross photographs, anterior segment optical computed tomography (AS-OCT) imaging, and tensile testing. A prospective study of human tarsus was performed on samples from patients undergoing wedge resection for floppy eyelid syndrome and was analyzed with AS-OCT and tensile testing.Results: 73 porcine adnexa and 9 patients (16 eyelids) who underwent wedge excision were included in the study. Grossly, greater stiffness was observed in crosslinked porcine tissue. AS-OCT imaging in porcine tissue showed a distinct hyperreflective band in crosslinked specimens whose area and intensity increased with longer treatment time (P = 0.003); this band was also visible in crosslinked human specimens. Tensile testing was performed, but results were not statistically significant.Conclusions: AS-OCT imaging, which has not been previously described for tarsal plate, showed a characteristic change in crosslinked porcine and human specimens. Tissue stiffness was increased grossly, but changes in tensile properties were not statistically significant. Further study is warranted to determine relevance as a potential treatment for floppy eyelid syndrome. [ABSTRACT FROM AUTHOR]

Background and Purpose: Depression affects millions of adolescents in the United States each year. This population may benefit from targeted preventive interventions. We sought to understand the internal factors that affect the ability of healthcare organizations to implement an intervention that involves mental health screening and depression prevention treatment of at-risk adolescents in primary care settings. Methods: From November 2011 to July 2016 we conducted a study of the implementation of a multisite (N=30) phase 3 randomized clinical trial of an Internet-based depression prevention intervention program (CATCH-IT). We describe the prevalence of internal barriers on the screening and enrollment process by reporting REACH (the proportion of target audience exposed to the intervention). Results: A total of 369 adolescents were randomized into the intervention or control program. Mean REACH values for the study clinics were 0.216 for screening and 0.181 for enrollment to CATCH-IT. Mean REACH enrollment lost due to internal barriers was 0.233. This translated to 4,691 adolescents lost at screening and 2,443 adolescents lost at enrollment due to internal barriers. Conclusion: We propose a model of the implementation process that emphasizes the importance of positive relational work that assists in overcoming internal barriers to REACH. We also provide implications for policy and practice. [ABSTRACT FROM AUTHOR]

Background: Medical educators, residents and administrators have increasing access to a large quantity of electronic resources. This content can augment and improve our teaching methods but can be difficult to consolidate and present. A multitude of electronic learning management systems are available to help organize and serve this content though never with small residency programs as the target userbase. As our residency program in Ophthalmology looked to consolidate our electronic resources and update our education methods, we evaluated and built an electronic learning management platform. Results: Faculty were interviewed to determine features they would find useful in curriculum management system and then various systems were investigated for features, cost and ease of use. Conclusions: Our solution has been both cost-effective and successful. Resident satisfaction is high and faculty utilization has been increasing. We present many customizations that increased success. Consideration of the specific needs of a program is paramount to choosing a cost effective solution that will be well received. [ABSTRACT FROM AUTHOR]

The advent of computer-assisted technology has revolutionized planning for complex craniofacial operations, including orbital reconstruction. Orbital reconstruction is ideally suited for virtual planning, as it allows the surgeon to assess the bony anatomy and critical neurovascular structures within the orbit, and plan osteotomies, fracture reductions, and orbital implant placement with efficiency and predictability. In this article, we review the use of virtual surgical planning for orbital decompression, posttraumatic midface reconstruction, reconstruction of a two-wall orbital defect, and reconstruction of a large orbital floor defect with a custom implant. The surgeon managing orbital pathology and posttraumatic orbital deformities can benefit immensely from utilizing virtual planning for various types of orbital pathology. [ABSTRACT FROM AUTHOR]