Iris melanoma in an Australian cohort.

BACKGROUND: To report the clinicopathological features and epidemiology of iris melanoma in Queensland, Australia. METHODS: This was a retrospective study of 86 patients with iris melanoma treated between 2001 and 2022 at the Queensland Ocular Oncology Service, Brisbane, Australia. Main outcome measures included demographics, clinical and phenotypic features, age-adjusted incidence and relative survival. RESULTS: Eighty-six patients (63% female) were included. Mean age was 54 years (range 17-82 years). The majority of patients (97%) were Caucasian, with blue eyes, fair skin and Fitzpatrick Skin Type I or II. Demographic features and clinical history showed a tendency for high ultraviolet radiation (UVR) exposure in the cohort. Histopathology was available in 69 cases (82%), and of these, 77% tumours were of spindle cell origin, with low-risk genetic profiles. Patients were followed for a mean of 8 years (median 7, range 1-21 years) after diagnosis, and only one case of metastasis was documented. CONCLUSIONS: The association of iris freckles, history of UVR exposure and dermatologic findings supports the role of UVR in iris melanoma. Occupation and avocation history, as well as evaluation of iris freckles may offer an easily accessible way of stratifying the risk of an individual for development of UVR-related uveal melanoma.

Efficacy of porcine acellular dermal matrix in the management of lower eyelid retraction: case series and review of the literature.

PURPOSE: To investigate the efficacy of Permacol™, a decellularized porcine dermal-derived membrane, as a spacer in the management of lower eyelid retraction. The efficacy of sizing and insertion was investigated, as well as complications. The literature was also reviewed to compare this material with other porcine-derived grafts in use for the management of lower eyelid retraction. METHODS: This was a retrospective case series observing all patients who received lower eyelid Permacol implants by the two senior authors (AAM, TGH) for the management of lower eyelid retraction. Patient demographics, indications for surgery, graft size, degree of postoperative lid advancement, and complications were reviewed. RESULTS: A total of 12 patients (16 eyelids) received Permacol implants for correction of lower eyelid retraction during the study period of 18 months (January 2015 to July 2017). Ten procedures were related to thyroid eye disease, 3 for reconstruction, 2 postcosmetic lower lid blepharoplasty, and one acquired anophthalmic socket. The average preoperative inferior scleral show (ISS) was 1.74 mm, and the average postoperative ISS was 0.82 mm. There was a mean lower eyelid elevation of 0.91 mm (p < 0.005, Wilcoxon signed rank test) and mean ratio of graft height:preoperative ISS was 3.8:1 over a median of 8 months follow-up. CONCLUSIONS: Permacol is a safe and effective alternative to autologous tissues for use as a spacer in patients with lower eyelid retraction of varying etiologies. It does undergo some resorption with time, however this can be predicted and incorporated into surgical planning; we recommend an implant height:ISS ratio of 4:1.

Temporary suture tarsorrhaphy at the time of orbital ball implantation.

PURPOSE: Conjunctival chemosis is a common, usually benign, complication of ocular and oculoplastic surgery. After enucleation, evisceration, or secondary ball implant, however, conjunctival edema can cause conformer extrusion, forniceal eversion, and shortening which may complicate the future fitting of a prosthesis. This longitudinal chart review aimed to estimate the efficacy of a temporary suture tarsorrhaphy to minimize postoperative edema and improve conformer retention. METHODS: We retrospectively reviewed the charts of 415 consecutive patients undergoing enucleation, evisceration, and secondary ball implantation between 1990 and 2016. Three-hundred twenty-eight patients had complete data which was analyzed for age, gender, surgical details, complications, and follow-up. RESULTS: We identified 328 eyes that underwent enucleation (48%), evisceration (3%), or secondary implantation (49%) during the study period. Eighty-nine patients had a suture tarsorrhaphy at the time of surgery, and 239 did not. There was a statistically significant incidence of postoperative conjunctival edema in the no tarsorrhaphy group. There was also a significantly increased rate of conformer loss associated with conjunctival edema. Need for further surgery was not uncommon with 64% and 43% of patients requiring a secondary procedure in the no tarsorrhaphy and tarsorrhaphy groups respectively. CONCLUSIONS: Temporary suture tarsorrhaphy is a simple and effective procedure that reduces conjunctival edema and increases conformer stability when performed at the time of enucleation, evisceration, or secondary ball implantation.

Recognition and Management of Acute Dacryocystic Retention.

PURPOSE: Acute noninfectious dacryocystic retention is an under-recognized condition heralded by painful lacrimal sac swelling, obstruction, and epiphora. This longitudinal chart review aimed to estimate the incidence of this condition in an urban Australian population, while further defining the signs and symptoms of the disease and options for management. METHODS: We retrospectively reviewed the charts of 1,593 consecutive patients presenting with acquired nasolacrimal duct obstruction and epiphora between 1990 and 2015. The records of patients with acute dacryocystic retention were analyzed for age, gender, clinical features, and management. RESULTS: Of all patients presenting with nasolacrimal duct obstruction, 20 were found to have acute dacryocystic retention. The mean age was 42.2 ± 9.3. There was an equal distribution of laterality, and only 2 cases (10%) were bilateral. There was a statistically significant female predominance, and most patients presented reporting 2 to 3 previous episodes. At presentation, 30% of patients reported spontaneous passage of a dacryolith. Despite this, 70% of affected patients required surgical management, with a 64% incidence of stones noted at the time of dacryocystorhinostomy. CONCLUSIONS: Acute dacryocystic retention is an uncommon, but even less frequently identified condition, most common in middle-aged women. Improved understanding of this condition and its natural history is likely to enhance patient counseling and avoid ineffective use of antibiotics in affected patients.

Combined photodynamic therapy and transpupillary thermotherapy for small choroidal melanoma.

OBJECTIVE: The objective of this study was to determine whether combining verteporfin-based photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) achieves adequate tumour control while maintaining visual acuity in individuals with small choroidal melanoma of amelanotic, melanotic, and variable pigmentation. DESIGN: Individuals with posterior choroidal melanomas up to 3 mm in height underwent verteporfin-based PDT followed by immediate TTT. Further combined laser therapy was performed if a poor response was noted at 12 weeks or beyond. Tumours that demonstrated significant further growth were treated with brachytherapy or enucleation. A total of 37 eyes of 37 patients from the Terrace Eye Centre in Brisbane, Australia were studied. Average age of participants was 59.62 ± 12.45 years, and 17 of 37 participants were female (46%). METHODS: This was a retrospective, noncomparative interventional study. RESULTS: Seven of the 37 participants (19%) had recurrence of their tumour requiring further brachytherapy or enucleation. There was no statistically significant difference in visual acuity before and after treatment. There were no baseline characteristics that predicted treatment outcome. Ten individuals developed complications including epiretinal membrane (16%), scotoma (8%), cataract (3%), and macular edema (3%). No individuals experienced extraocular extension or progressed to metastatic disease. The mean follow-up time was 49 months. CONCLUSION: Combined PDT and TTT achieved 81% tumour control in this study while preserving visual acuity. However, higher rates of local recurrence compared with brachytherapy warrant close follow-up to identify recurrences early.

Germline Variants in Patients Affected by Both Uveal and Cutaneous Melanoma.

Uveal melanoma (UM) and nonacral cutaneous melanoma (CM) are distinct entities with varied genetic landscapes despite both arising from melanocytes. There are, however, similarities in that they most frequently affect people of European ancestry, and high penetrance germline variants in BAP1, POT1 and CDKN2A have been shown to predispose to both UM and CM. This study aims to further explore germline variants in patients affected by both UM and CM, shedding light on the underlying genetic mechanism causing these diseases. Using exome sequencing we analysed germline DNA samples from a cohort of 83 Australian patients diagnosed with both UM and CM. Eight (10%) patients were identified that carried pathogenic mutations in known melanoma predisposition genes POT1, MITF, OCA2, SLC45A2 and TYR. Three (4%) patients carried pathogenic variants in genes previously linked with other cancer syndromes (ATR, BRIP1 and MSH6) and another three cases carried monoallelic pathogenic variants in recessive cancer genes (xeroderma pigmentosum and Fanconi anaemia), indicating that reduced penetrance of phenotype in these individuals may contribute to the development of both UM and CM. These findings highlight the need for further studies characterising the role of these genes in melanoma susceptibility.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Irritant bullous contact dermatitis caused by a rove beetle: an illustrated clinical course.

A 26-year-old Australian female traveller in Sierra Leone presented with an irritant bullous contact dermatitis consistent with paederus dermatitis. The lesions were treated with a potent topical corticosteroid with good effect. The affected area resolved in 6 weeks and hyperpigmention persisted for months until complete resolution. This dermatitis occurs when beetles of the genus Paederus (rove beetles) are crushed on the skin, releasing pederin. The same dermatitis ensues with Australian Paederus species. Serial clinical photographs are presented which will aid Australian dermatologists in the diagnosis of this dermatitis, which presents in regional Australian patients and returned overseas travellers.

Machine Learning Techniques, Applications, and Potential Future Opportunities in Pressure Injuries (Bedsores) Management: A Systematic Review.

Pressure Injuries (PI) are one of the most common health conditions in the United States. Most acute or long-term care patients are at risk of developing PI. Machine Learning (ML) has been utilized to manage patients with PI, in which one systematic review describes how ML is used in PI management in 32 studies. This research, different from the previous systematic review, summarizes the previous contributions of ML in PI from January 2007 to July 2022, categorizes the studies according to medical specialties, analyzes gaps, and identifies opportunities for future research directions. PRISMA guidelines were adopted using the four most common databases (PubMed, Web of Science, Scopus, and Science Direct) and other resources, which result in 90 eligible studies. The reviewed articles are divided into three categories based on PI time of occurrence: before occurrence (48%); at time of occurrence (16%); and after occurrence (36%). Each category is further broken down into sub-fields based on medical specialties, which result in sixteen specialties. Each specialty is analyzed in terms of methods, inputs, and outputs. The most relevant and potentially useful applications and methods in PI management are outlined and discussed. This includes deep learning techniques and hybrid models, integration of existing risk assessment tools with ML that leads to a partnership between provider assessment and patients' Electronic Health Records (EHR).

An Integrated System of Multifaceted Machine Learning Models to Predict If and When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

Hospital-Acquired Pressure Injury (HAPI), known as bedsore or decubitus ulcer, is one of the most common health conditions in the United States. Machine learning has been used to predict HAPI. This is insufficient information for the clinical team because knowing who would develop HAPI in the future does not help differentiate the severity of those predicted cases. This research develops an integrated system of multifaceted machine learning models to predict if and when HAPI occurs. Phase 1 integrates Genetic Algorithm with Cost-Sensitive Support Vector Machine (GA-CS-SVM) to handle the high imbalance HAPI dataset to predict if patients will develop HAPI. Phase 2 adopts Grid Search with SVM (GS-SVM) to predict when HAPI will occur for at-risk patients. This helps to prioritize who is at the highest risk and when that risk will be highest. The performance of the developed models is compared with state-of-the-art models in the literature. GA-CS-SVM achieved the best Area Under the Curve (AUC) (75.79 ± 0.58) and G-mean (75.73 ± 0.59), while GS-SVM achieved the best AUC (75.06) and G-mean (75.06). The research outcomes will help prioritize at-risk patients, allocate targeted resources and aid with better medical staff planning to provide intervention to those patients.

An Integrated System of Braden Scale and Random Forest Using Real-Time Diagnoses to Predict When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

BACKGROUND AND OBJECTIVES: Bedsores/Pressure Injuries (PIs) are the second most common diagnosis in healthcare system billing records in the United States and account for 60,000 deaths annually. Hospital-Acquired Pressure Injuries (HAPIs) are one classification of PIs and indicate injuries that occurred while the patient was cared for within the hospital. Until now, all studies have predicted who will develop HAPI using classic machine algorithms, which provides incomplete information for the clinical team. Knowing who will develop HAPI does not help differentiate at which point those predicted patients will develop HAPIs; no studies have investigated when HAPI develops for predicted at-risk patients. This research aims to develop a hybrid system of Random Forest (RF) and Braden Scale to predict HAPI time by considering the changes in patients' diagnoses from admission until HAPI occurrence. METHODS: Real-time diagnoses and risk factors were collected daily for 485 patients from admission until HAPI occurrence, which resulted in 4619 records. Then for each record, HAPI time was calculated from the day of diagnosis until HAPI occurrence. Recursive Feature Elimination (RFE) selected the best factors among the 60 factors. The dataset was separated into 80% training (10-fold cross-validation) and 20% testing. Grid Search (GS) with RF (GS-RF) was adopted to predict HAPI time using collected risk factors, including Braden Scale. Then, the proposed model was compared with the seven most common algorithms used to predict HAPI; each was replicated for 50 different experiments. RESULTS: GS-RF achieved the best Area Under the Curve (AUC) (91.20 ± 0.26) and Geometric Mean (G-mean) (91.17 ± 0.26) compared to the seven algorithms. RFE selected 43 factors. The most dominant interactable risk factors in predicting HAPI time were visiting ICU during hospitalization, Braden subscales, BMI, Stimuli Anesthesia, patient refusal to change position, and another lab diagnosis. CONCLUSION: Identifying when the patient is likely to develop HAPI can target early intervention when it is needed most and reduces unnecessary burden on patients and care teams when patients are at lower risk, which further individualizes the plan of care.

Conjunctival Lymphoma.

Lymphoma of the conjunctiva is an ocular malignancy derived from clonal proliferation of lymphocytes. The majority of conjunctival lymphoma is extranodal marginal zone B-Cell lymphoma (EMZL), however diffuse large B-cell (DLBCL), follicular (FL), mantle cell (MCL) and T- cell subtypes are also seen. Clinical manifestations are non-specific, but include unilateral or bilateral painless salmon-pink conjunctival lesions. Approaches to treatment have centered around local immunomodulation, often with Interferon-α2b or Rituximab (anti-CD20 monoclonal antibody) with or without radiation. Although conjunctival lymphoma is generally considered an indolent disease, recent advances in next-generation sequencing have improved clinicians' ability to predict future recurrence or systemic disease through assessment of cytogenic and molecular features. In this paper, we review the classification, clinical features, diagnostic techniques, and emerging strategies for management and prognostication of conjunctival lymphomas.

A Hybrid System of Braden Scale and Machine Learning to Predict Hospital-Acquired Pressure Injuries (Bedsores): A Retrospective Observational Cohort Study.

Background: The Braden Scale is commonly used to determine Hospital-Acquired Pressure Injuries (HAPI). However, the volume of patients who are identified as being at risk stretches already limited resources, and caregivers are limited by the number of factors that can reasonably assess during patient care. In the last decade, machine learning techniques have been used to predict HAPI by utilizing related risk factors. Nevertheless, none of these studies consider the change in patient status from admission until discharge. Objectives: To develop an integrated system of Braden and machine learning to predict HAPI and assist with resource allocation for early interventions. The proposed approach captures the change in patients' risk by assessing factors three times across hospitalization. Design: Retrospective observational cohort study. Setting(s): This research was conducted at ChristianaCare hospital in Delaware, United States. Participants: Patients discharged between May 2020 and February 2022. Patients with HAPI were identified from Nursing documents (N = 15,889). Methods: Support Vector Machine (SVM) was adopted to predict patients' risk for developing HAPI using multiple risk factors in addition to Braden. Multiple performance metrics were used to compare the results of the integrated system versus Braden alone. Results: The HAPI rate is 3%. The integrated system achieved better sensitivity (74.29 ± 1.23) and detection prevalence (24.27 ± 0.16) than the Braden scale alone (sensitivity (66.90 ± 4.66) and detection prevalence (41.96 ± 1.35)). The most important risk factors to predict HAPI were Braden sub-factors, overall Braden, visiting ICU during hospitalization, and Glasgow coma score. Conclusions: The integrated system which combines SVM with Braden offers better performance than Braden and reduces the number of patients identified as at-risk. Furthermore, it allows for better allocation of resources to high-risk patients. It will result in cost savings and better utilization of resources. Relevance to clinical practice: The developed model provides an automated system to predict HAPI patients in real time and allows for ongoing intervention for patients identified as at-risk. Moreover, the integrated system is used to determine the number of nurses needed for early interventions. Reporting Method: EQUATOR guidelines (TRIPOD) were adopted in this research to develop the prediction model. Patient or Public Contribution: This research was based on a secondary analysis of patients' Electronic Health Records. The dataset was de-identified and patient identifiers were removed before processing and modeling.

Conjunctival Merkel cell carcinoma: case report and review of the literature.

Merkel cell carcinoma (MCC) of the conjunctiva is rare. We report the case of a 73-year-old man who presented with unilateral foreign body sensation and blurred vision. A rapidly enlarging conjunctival lesion was identified and excised. The histopathological diagnosis was poorly differentiated squamous cell carcinoma, later reclassified as neuroendocrine / Merkel cell carcinoma following excision on subsequent recurrence. The patient developed lymph node and widespread metastatic disease. The challenges of diagnosing MCC at this site are discussed and the literature on treatment options for this aggressive disease is reviewed.

Choroidal melanoma with synchronous Fuchs' adenoma and novel ATRX mutation.

BACKGROUND: To report a case of Fuchs' adenoma occurring in an eye with a large choroidal melanoma. We have reviewed the literature to describe the clinical presentation, ultrasound characteristics and pathological features of these entities. CASE PRESENTATION: A 69-year-old Caucasian man presented with vision loss from a large choroidal melanoma. Enucleation showed an incidental Fuchs' adenoma in the same eye. Whole-exome sequence analysis was also performed on the patient's blood and melanoma, which showed a rarely-reported ATRX mutation. CONCLUSIONS: Fuchs' adenoma is an under-diagnosed benign age-related hyperplasia of the non-pigmented ciliary epithelium (NPCE). Given its location and characteristics, it can be mistaken for choroidal melanoma and clinicians are reminded how to differentiate between these pathologies and that they may co-exist.

Ocular Surface Fibroma: Clinical, Histopathological, and Immunohistochemical Features of 10 Cases.

AIM: To describe the clinical, histological, and immunohistochemical (IHC) features of a series of 10 cases of ocular surface fibroma (OSF) and correlate the findings with other similar histological entities. METHOD: The patient demographics and features of the lesions were analysed from the clinical notes. All cases in the series had routine diagnostic excisional biopsies with standard histopathological and IHC evaluation. Each case was analysed by histology and immunohistochemistry with antibodies to: CD34, Factor XIIIa, desmin, smooth muscle actin, S100, Melan-A, ß-catenin, neurofilament, and Ki67. RESULTS: OSF occurred on the bulbar, tarsal, or forniceal conjunctiva, and typically presented as a white, pink, or yellow sheet-like or nodular lesion. The most common symptom was irritation or a foreign-body sensation. Lesions ranged in size from 4 to 13 mm. Only 1/10 cases showed a recurrence after an incomplete excision. Histologically, OSF comprised bland spindle cells in a collagen stroma. The spindle cells were CD34-positive (in 10/10 cases) and a smaller subset was positive for Factor XIIIa (6/10 cases). Normal resident spindle cells in the conjunctival stroma, Tenon's capsule, and tarsal plate were positive for CD34 and Factor XIIIa, implicating these cells in the origin of OSF. CONCLUSION: OSF is a benign lesion of resident CD34- and Factor XIIIa-positive spindle cells in the conjunctiva and Tenon's capsule. We have called to attention another lesion to be included by clinicians in the differential diagnosis of benign ocular surface lesions composed of CD34- and Factor XIIIa-positive spindle cells.

Management of recurrent sebaceous gland carcinoma.

OBJECTIVE: To evaluate the incidence and management of recurrent periocular sebaceous gland carcinoma at a tertiary ocular oncology service in the United Kingdom. METHODS: This was a retrospective cohort study of 62 patients with sebaceous gland carcinoma treated between 2004 and 2017. A total of 10 eyes were treated for local recurrence. The following variables were recorded: age and sex of patient; tumour location, histological subtype; recurrence type; treatment and outcome. RESULTS: Of the 62 cases with eyelid SGC, 10 (16%) had recurrences during the study period and satisfied inclusion criteria. There were six (60%) females and four males in the recurrent group. The mean time interval between initial excision and tumour recurrence was 37 months (median 23 months; range 4 to 84 months). Four patients received cryotherapy to the lids and conjunctiva to control recurrent disease and two patients were treated with topical or intralesional chemotherapy. Four patients (40%) underwent orbital exenteration during the study period. Metastasis occurred in 20% over a mean follow-up of 113 months (median 106; range 47-184 months). CONCLUSIONS: The risk factors for local recurrence of SGC after wide excision with paraffin section control were reported, and an approach to these recurrent lesions was proposed. The results of this study will help guide surgeons dealing with the medical and surgical conundrum of recurrent disease. The risk of recurrence is highest in the first 2 years after initial excision.

Genomic analysis of adult case of ocular surface giant congenital melanocytic nevus and associated clinicopathological findings.

INTRODUCTION: Conjunctival nevi are the most common tumor of the ocular surface. There are some rare reports of so-called 'giant' conjunctival nevi. We report a case of a 47-year-old female with a cutaneous and ocular surface giant congenital melanocytic nevus and describe her clinical course. CASE DESCRIPTION: This is a retrospective case report of a single patient. A 47-year-old female with a history of biopsy-proven periorbital congenital melanocytic nevus, with an associated giant conjunctival nevus presented for structural and functional rehabilitation. Serial surgeries were performed and excised tissue was sent for histopathological and genetic examination. The conjunctival nevus had a low tumor mutation burden, and of the 647 somatic mutations, only one occurred within a protein coding region, namely NRAS p.Gln61Arg. CONCLUSION: This is the first reported adult case including genomic analysis of an ocular surface giant congenital melanocytic nevus. The case shows a possible association between periorbital congenital melanocytic nevi and giant conjunctival nevi, and underscores the possible role that targeted drug therapies may have in malignant transformation of these conditions.

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).