The inbetweeners: a review of the transition from child into adult care for young people with chronic health conditions.

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.

Disordered activity? A review of the quality of epilepsy care provided to adults presenting to hospital with a seizure.

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.

Durable tumor regression and restoration of neurologic function after treatment with anti-PD-1 in patients with functionally unresectable cutaneous squamous cell carcinoma with perineural spread into the cavernous sinus.

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.

Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device.

The dacryocystorhinostomy procedure creates a direct passageway between the lacrimal sac and nasal cavity, bypassing any nasolacrimal duct obstruction. Use of a continuous positive airway pressure device after dacryocystorhinostomy can cause nasolacrimal air regurgitation. Here, we report a case of air regurgitation after dacryocystorhinostomy that was successfully treated with placement of a Mini Monoka device, a silicone stent used in nasolacrimal surgery to prevent closure of the passageway, in a patient using a continuous positive airway pressure machine. Following the procedure, the patient was able to resume use of her continuous positive airway pressure device. CITATION: Srivatsan S, Mirza M, Imayama I, Setabutr P, Mahoney NR. Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device. J Clin Sleep Med. 2023;19(12):2123-2124.

Severe Mpox Infection of the Eye and Periocular Region.

Mpox is an emerging zoonotic infection with potentially severe ocular and periocular consequences, particularly in immunocompromised patients. This report summarizes 2 cases of fulminant mpox presenting in patients with AIDS. In the first case, confluent lesions resulted in orbital compartment syndrome and total eyelid necrosis. In the second case, eyelid involvement was accompanied by corneal melt and perforation. Despite aggressive medical and surgical treatment, both patients developed permanent loss of vision and ultimately expired.

Trends in Long-Term Ventilation Care in U.K. Children and Young People-Further Consideration Required for Pediatric Critical Care Services.

OBJECTIVES: The objective was to compare specific data from the 2020 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report "Balancing the Pressures" with two previous U.K. studies and to examine changes in the pediatric population requiring long-term ventilation (LTV) as well as the types delivered. We believe that the new data presented will facilitate future service planning. DESIGN: A subset of confidential enquiry data derived from a study by a nationally funded quality improvement organization (NCEPOD: www.ncepod.org.uk ) was compared with two previous U.K. datasets. SETTING: Healthcare providers across England, Wales, and Northern Ireland-inpatient and community settings. PATIENTS: Children and young people (CAYP) 0-16 years old receiving LTV between April 1, 2016, and March 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: When comparing the NCEPOD data with that last published in the United Kingdom, the number of CAYP requiring LTV more than doubled between 2008 and 2018 (933-2,093). There has also been a particular increase in the proportion of children that were under two when they were commenced on LTV (26-39.2%). Children are now more likely than previously to be receiving LTV to manage upper airway obstruction and CNS conditions. There has also been an approximate doubling of those receiving LTV over the whole 24-hour period (9.4-18.4%). CONCLUSIONS: The increased numbers and changing characteristics of babies and children requiring LTV over the last 3 decades in the United Kingdom have implications for all healthcare sectors but particularly for providers of critical care services.

Multiple Retinal Emboli and Medial Canthal Swelling Following Injection of Acellular Porcine Urinary Bladder Matrix for Hair Restoration.

Acellular porcine urinary bladder matrix promotes wound healing and is also used to stimulate hair growth. A 64-year-old female presented with acute-onset OD pain and decreased visual acuity after subcutaneous injection of acellular porcine urinary bladder matrix at the hairline. Fundus examination revealed multiple emboli at retinal arcade branch points, and fluorescein angiography demonstrated corresponding areas of peripheral nonperfusion. Two weeks later, external examination revealed new swelling of the right medial canthus without erythema or fluctuance, which was felt to possibly represent recruitment of vessels after occlusion in the facial vasculature. At 1-month follow up, visual acuity of the OD improved with resolution of right medial canthal swelling. Fundus examination was normal with no visible emboli. Herein, the authors present a case of retinal occlusion and medial canthal swelling following injection of acellular porcine urinary bladder matrix for hair restoration, which to the authors knowledge has not been previously reported.

National trends in surgical subspecialisation in ophthalmology in the USA.

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.

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.

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.

Clinicopathologic and Proteomic Analysis of Amyloidomas Involving the Ocular Surface and Adnexa.

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.

Epidemiologic Trends in Oculoplastics-Related Emergency Department Visits in the United States, 2006-2015.

PURPOSE: To characterize demographics and trends in oculoplastics-related emergency department (ED) visits. METHODS: The authors conducted a retrospective, multiyear study of the nationwide ED sample database. The nationwide ED sample was queried for oculoplastics-related International Classification of Disease-ninth revision codes identified from a comprehensive list and categorized based on anatomic location, urgency, and trauma status. Demographics, clinical characteristics, procedure requirement, and cost data were analyzed. Variables associated with inpatient admission were assessed using univariate and multivariate logistic regression. RESULTS: The authors identified an estimated 4.2 million ED visits in the United States with oculoplastics-related primary diagnoses, of which pathology was 80.8% eyelid/adnexal, 17.4% orbital, and 1.74% lacrimal. Overall, 31.3% of the visits were deemed to be nonurgent. Orbital pathology was more likely to be caused by trauma (70.6%), to be urgent (98.0%), and to require a procedure (45.6%) (p < 0.001). While less than 5% of all patients required hospitalization, predictors for inpatient admission were urgent diagnoses (odds ratio, 14.9; CI, 13.7-16.1), presentation to a level 1 trauma center (odds ratio, 3.19; CI, 2.7-3.79), and presence of orbital pathology (odds ratio, 6.09; CI 5.73-6.47). Incidence of ED visits decreased in all categories; however, total inflation-adjusted charges increased. CONCLUSIONS: Over half of oculoplastics-related ED visits are for trauma, with orbital pathology being less common but requiring a high level of care. Although trends show a potentially decreasing incidence of oculoplastics-related ED visits, increasing costs and high proportion of nonurgent visits pose an opportunity for mitigating periocular trauma and increasing outpatient access to care, respectively.

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.

Sensorineural Hearing Loss After Teprotumumab Therapy for Thyroid Eye Disease: A Case Report.

BACKGROUND AND OBJECTIVE: Teprotumumab is a fully human IgG1 monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R). It has been approved by the FDA to treat thyroid eye disease (TED) by reducing extraocular muscle and orbital fat volume. In clinical trials, hearing loss was noted as a side effect in 7 to 12% of patients, but no formal audiometric investigations of these patients were reported. Furthermore, the FDA and manufacturer offer no formal guidelines for audiometric monitoring. This case report is the first to describe sensorineural hearing loss (SNHL) in a patient undergoing treatment with teprotumumab. PATIENT: A 77-year-old woman presenting with bilateral SNHL after treatment with teprotumumab therapy for TED. INTERVENTION: Audiometric testing was performed due to worsening and prolonged SNHL after subsequent teprotumumab infusions. MAIN OUTCOME MEASURES: Word recognition scores, pure tone average. RESULTS: Audiometry after discontinuation of therapy showed moderate to moderate-severe SNHL with word recognition scores of 64% in the right ear and 68% in the left ear. CONCLUSIONS: There are currently no formal guidelines for routine audiograms before, during, and after infusion of teprotumumab. Given that such guidelines exist for ototoxic medications such as gentamicin and cisplatin, we strongly encourage audiometric monitoring for patients undergoing treatment with teprotumumab.

Transcriptomic Profiling of Control and Thyroid-Associated Orbitopathy (TAO) Orbital Fat and TAO Orbital Fibroblasts Undergoing Adipogenesis.

Purpose: Orbital fat hyperplasia commonly occurs in thyroid-associated orbitopathy (TAO). To understand molecular mechanisms underlying orbital adipogenesis, we used transcriptomics to compare gene expression in controls and patients with TAO, as well as in orbital fibroblasts (OFs) undergoing adipogenic differentiation. Methods: We performed bulk RNA sequencing (RNA-Seq) on intraconal orbital fat from controls and patients with TAO. We treated cultured OFs derived from patients with TAO with adipogenic media to induce adipogenesis. We used single nucleus RNA-Seq (snRNA-Seq) to profile treated and control OFs, identifying genes that are dynamically expressed during orbital adipogenesis in vitro, and compared these results to data from control and TAO orbital fat. Results: Gene expression profiles in control and TAO orbital fat are distinct. Signaling pathways including PI3K-Akt signaling, cAMP signaling, AGE-RAGE signaling, regulation of lipolysis, and thyroid hormone signaling are enriched in orbital fat isolated from patients with TAO. SnRNA-Seq of orbital fibroblasts undergoing adipogenesis reveals differential expression of the adipocyte-specific genes FABP4/5, APOE, PPARG, and ADIPOQ during adipogenic differentiation. The insulin-like growth factor-1 receptor and Wnt signaling pathways appear to be enriched early in adipogenesis. Gene modules that are enriched in TAO orbital fat are upregulated in orbital adipocytes during differentiation in vitro, whereas genes that are enriched in control orbital fat are enriched in undifferentiated OFs. Conclusions: We identified pathways enriched in TAO orbital fat, and dynamic changes in gene expression that occur during adipogenic differentiation of orbital fibroblasts. These findings may help guide functional studies of genes and pathways critical for orbital adipogenesis.

Temperature and species-dependent regulation of browning in retrobulbar fat.

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.

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.

Clinical Characteristics and Outcomes in Patients Undergoing Primary or Secondary Enucleation or Evisceration After Ocular Trauma.

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.

Balancing the pressures: a review of the quality of care provided to children and young people aged 0-24 years who were receiving long-term ventilation.

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.