Apoptotic Marker Expression of Resected Lacrimal Gland Adenoid Cystic Carcinoma Tumor Margins After Intra-arterial Chemotherapy and Globe-Sparing Excision.

PURPOSE: Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare orbital malignancy with devastating lethality. Neoadjuvant intra-arterial chemotherapy (IACC) has demonstrated cytoreductive effects on LGACC macroscopically, but limited studies have examined cellular and molecular determinants of the cytoreductive effect. This post hoc study assessed apoptotic marker expression on excised tumor specimens after neoadjuvant IACC and globe-sparing resection, emphasizing the examination of tumor margins. METHODS: This retrospective study identified LGACC specimens resected in a globe-sparing technique after neoadjuvant IACC by reviewing the Florida Lions Ocular Pathology database at Bascom Palmer Eye Institute. Histopathology slides of the specimens were re-examined to confirm the diagnosis and identify the tumor margin. Immunofluorescent staining was performed for apoptotic markers, including P53, cleaved caspase-3, cleaved PARP-1, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Positive expression was determined by comparison to the negative control. RESULTS: Tumor specimens from 5 patients met inclusion criteria. All 5 cases were positive at the center and the margin for TUNEL, p53, and cleaved caspase-3. One case did not show positive expression of cleaved PARP-1 at the margin but was positive for the other apoptotic markers. CONCLUSIONS: This post hoc study demonstrated positive staining for multiple apoptotic markers in post-IACC tumor specimens at the tumor center and margin. Apoptotic marker expression along the margins of post-treatment specimens is important, as it may offer surrogate information to speculate on the state of residual cancer cells adjacent to the excision margin inadvertently remaining in the orbit.

Vectorized instructive signals in cortical dendrites during a brain-computer interface task.

Backpropagation of error is the most widely used learning algorithm in artificial neural networks, forming the backbone of modern machine learning and artificial intelligence1,2. Backpropagation provides a solution to the credit assignment problem by vectorizing an error signal tailored to individual neurons. Recent theoretical models have suggested that neural circuits could implement backpropagation-like learning by semi-independently processing feedforward and feedback information streams in separate dendritic compartments3-7. This presents a compelling, but untested, hypothesis for how cortical circuits could solve credit assignment in the brain. We designed a neurofeedback brain-computer interface (BCI) task with an experimenter-defined reward function to evaluate the key requirements for dendrites to implement backpropagation-like learning. We trained mice to modulate the activity of two spatially intermingled populations (4 or 5 neurons each) of layer 5 pyramidal neurons in the retrosplenial cortex to rotate a visual grating towards a target orientation while we recorded GCaMP activity from somas and corresponding distal apical dendrites. We observed that the relative magnitudes of somatic versus dendritic signals could be predicted using the activity of the surrounding network and contained information about task-related variables that could serve as instructive signals, including reward and error. The signs of these putative teaching signals both depended on the causal role of individual neurons in the task and predicted changes in overall activity over the course of learning. These results provide the first biological evidence of a backpropagation-like solution to the credit assignment problem in the brain.

Patients With Dragged Optic Disc Vessels and Retinal Folds: Clinical Features, Multimodal Imaging, and Histopathology.

BACKGROUND AND OBJECTIVE: To describe the multimodal imaging and histopathological features of patients with dragged optic disc vessels (DODV). PATIENTS AND METHODS: This is a retrospective, observational analysis using multimodal imaging of eyes with DODV in patients with retinal vascular diseases including familial exudative vitreoretinopathy, inflammatory disease, and others. In addition, two additional enucleated eyes with DODV underwent histopathological analysis. RESULTS: Of the 13 patients, eight were girls and five were boys. Mean age was 5 years (ranging from 4 months to 10 years old). Of the 15 eyes, 12 (80%) demonstrated temporal dragging and three (20%) had nasal dragging. Retinal vascular abnormalities were present in 11 of the fellow eyes. Multimodal imaging demonstrated features of DODV including direction of traction, outer retinal thickening, increased flow, and other features. Only two (13.3%) eyes required surgical intervention. Mean follow-up was 14 (range 3 to 30 months) months. At last follow-up all eyes remained stable. Last visual acuity ranged from 20/100 to counting fingers. As well, two enucleated globes of adults with retinopathy of prematurity underwent histopathologic evaluation, showing optic nerve fibers that extended from the optic nerve into the DODV. CONCLUSIONS: DODV is a sign of various late-stage retinal vascular diseases, associated with poor visual function. Multimodal imaging and histopathology can assist in understanding the disease pathology. [Ophthalmic Surg Lasers Imaging Retina 2023;54:634-642.].

Evaluation of Patients Referred for Abnormal Digital Rectal Examination With Normal Prostate-Specific Antigen on Best Timed Pathway for Prostate Cancer.

Introduction Currently, there is no recommendation for adjustments to the Best Timed Pathway for Prostate cancer (BTiPP) depending on whether the referral is for raised prostate-specific antigen (PSA) or malignant-feeling prostate on digital rectal examination (DRE). Therefore, all patients undergo MRI scanning. We aim to establish if patients with abnormal DRE only (without raised PSA) should have an adjusted pathway by comparing the biopsy rate and diagnostic yield after an MRI scan. Methods All BTiPP 2021 referral patient notes were reviewed. The patients were categorized into the aDRE group (abnormal DRE with normal PSA) or the rPSA group (raised PSA with or without abnormal DRE). Data and results for MRI and prostate biopsy were evaluated. Diagnostic yield was defined as the percentage of patients who underwent an MRI, who were diagnosed with biopsy-proven cancer. Results 68.5% (74/108) and 70.9% (282/398) of patients underwent upfront MRI in the aDRE and rPSA groups, respectively. Following MRI, the biopsy rate (28.4% (21/74) vs. 42.9% (121/282) (p=0.02)) and the biopsy-proven diagnostic yield (20.3% (15/74) vs. 36.9% (104/282) (p<0.01)) were both significantly lower in the aDRE group. 58% (43/74) of patients in the aDRE group had no posterior lesions on MRI. Only 6.7% (1/15) of biopsy-proven cancers in the aDRE group were solely anterior. Conclusions After MRI, the biopsy rate and diagnostic yield were significantly lower in the aDRE group compared to the rPSA group. Furthermore, a majority of patients referred for aDRE had a normal posterior prostate appearance on MRI. An adjusted pathway for patients referred for aDRE with normal PSA, with DRE by a urologist prior to MRI, should be considered as it would likely reduce unnecessary investigations, treatment, and patient anxiety. These data suggest that this would not risk missing significant cancers.

Utilization of Ophthalmic Management in Patients with Head-and-Neck Trauma Secondary to Firearms.

Introduction: This retrospective cohort study presents the epidemiology of severe firearm-related ophthalmic injury and the level of ophthalmology involvement in the multidisciplinary management of head-and-neck gunshot injuries. Methods: A retrospective study identified 207 patients with firearm-related injuries involving the head and neck treated at an Academic Tertiary Care Institution from 2010 to 2020. Results: Ophthalmology consulted on 29% of patients with head-and-neck firearm injuries. At least one of the services managing facial trauma (plastic surgery and otolaryngology) consulted on 71.5% of cases (P < 0.001). Of patients evaluated by ophthalmology, 93.3% survived to discharge; 78.2% of patients who were not evaluated survived to discharge (P = 0.009). Ophthalmology consulted on all patients with open globe injury (10.6%) (P < 0.001), all of which were evaluated by the facial trauma service (P = 0.002), 77.3% by otolaryngology (P = 0.42), 50% by neurosurgery, 36.4% by plastic surgery, 13.6% by orthopedic surgery, and 4.5% by vascular surgery. Ophthalmology consulted on 76.5% of patients with orbital fracture (32.9%) (P < 0.001); 83.8% were evaluated by the facial trauma service (P = 0.006), 69.1% by otolaryngology (P = 0.014), 54.4% by neurosurgery, 27.9% by plastic surgery, 10.3% by orthopedic surgery, and 2.9% by vascular surgery. For patients with orbital fractures, 92.3% survived when ophthalmology was consulted (P = 0.698); 43.8% survived when not consulted (P = 0.001). Conclusions: Firearm-related injuries of the head and neck frequently involve ocular and orbital structures, often causing serious vision-threatening injuries. Multispecialty management is common and early ophthalmology specialist evaluation and co-management are indicated to best identify ophthalmic injuries.

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis.

Background: In patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is. Methods: We systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex. Results: We included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs (n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002). Conclusion: SGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes.

Presentation of a Smooth Muscle Hamartoma in the Bulbar Conjunctiva of an Adolescent Boy: A Case Report and Review of Literature.

PURPOSE: The aim of this study was to describe a novel presentation of conjunctival smooth muscle hamartoma and review the histopathologic findings of this entity. METHODS: A 17-year-old African American adolescent boy presented with a pink, nontender lesion of the right bulbar conjunctiva that did not improve with medical management. He had no previous medical or ocular history. The lesion was excised. RESULTS: Histopathologic examination disclosed morphologically benign smooth muscle bundles within the substantia propria that stained positively for smooth muscle actin, vimentin, and desmin consistent with the diagnosis of a smooth muscle hamartoma. CONCLUSIONS: Although congenital smooth muscle hamartomas of the conjunctiva have been rarely reported in the literature, this is the first described case of a smooth muscle hamartoma presenting in adolescence in the bulbar conjunctiva. This lesion should be considered in the differential diagnosis for adolescents with similar appearing lesions.

Hypercalcemia-leukocytosis syndrome from non-schistosomiasis-associated squamous cell carcinoma of the urinary bladder: a case report and review of the literature.

BACKGROUND: Non-schistosomiasis-associated squamous cell carcinoma of the urinary bladder is less common in the Western world. Limited information on its possible paraneoplastic syndromes exists. Leukocytosis tends to commonly be regarded by clinicians as an indication of sepsis, rather than a feature of paraneoplasia, potential surrogate marker for recurrence, and prognostic marker. Accompanying hypercalcemia may be missed entirely. CASE PRESENTATION: A 66-year-old Caucasian man presented with visible painless hematuria and symptomatic hypercalcemia. Investigations revealed a squamous cell carcinoma of the urinary bladder with marked leukocytosis. Hypercalcemia and leukocytosis resolved following radical cystectomy, recurred with nodal recurrence and regressed with radiotherapeutic control. Subsequently, serum leukocyte and calcium assays were included in his follow-up protocol. His survival was 20 months by the time of the report. CONCLUSION: This report highlights hypercalcemia-leukocytosis syndrome as a paraneoplastic manifestation of non-schistosomiasis-associated squamous cell carcinoma to reemphasize the need for clinicians to assay for calcium in the presence of leukocytosis in such patients. Prompt identification and control of the paraneoplastic derangements, with treatment of the cancer recurrence it may connote, is advocated to provide a chance for better long-term outcomes in these patients.

Transcatheter Aortic Valve Replacement-Associated Acute Kidney Injury: An Update.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a relatively novel minimally invasive procedure for the treatment of symptomatic patients with severe aortic stenosis. Although it has been proven effective in improving mortality and quality of life, TAVR is associated with serious complications, such as acute kidney injury (AKI). SUMMARY: TAVR-associated AKI is likely due to several factors such as sustained hypotension, transapical approach, volume of contrast use, and baseline low GFR. This narrative review aims to present an overview of the latest literature and evidence regarding the definition of TAVR-associated AKI, its risk factors, and its impact on morbidity and mortality. The review used a systematic search strategy with multiple health-focused databases (Medline, EMBASE) and identified 8 clinical trials and 27 observational studies concerning TAVR-associated AKI. Results showed that TAVR-associated AKI is linked to several modifiable and nonmodifiable risk factors and is associated with higher mortality. A variety of diagnostic imaging modalities have the potential to identify patients at high risk for development of TAVR-AKI; however, there are no existing consensus recommendations regarding their use as of this time. The implications of these findings highlight the importance of identifying high-risk patients for which preventive measures may play a crucial role, and should be maximized. KEY MESSAGE: This study reviews the current understanding of TAVR-associated AKI including its pathophysiology, risk factors, diagnostic modalities, and preventative management for patients.

Osteolytic sarcoidosis of the orbit without pulmonary involvement.

A 69-year-old woman with a history of a left orbital mass presented to the emergency room with progressive breakthrough pain in her left orbit despite medical therapy. On examination, there was extraocular motility restriction with diplopia upon left supraduction. Computed tomography (CT) scan of the orbits revealed soft tissue thickening of the left medial and superior periorbita and left lacrimal fossa; bony erosion of the left frontal bone, left orbital roof, and left lamina papyracea; and bilateral mass-like enlargement of the extraocular muscles. An orbitotomy with incisional biopsy was performed, and histopathological examination revealed non-caseating granulomatous inflammation consistent with sarcoidosis. Chest imaging demonstrated no sequela of pulmonary sarcoidosis, and her serum angiotensin converting enzyme (ACE) level was within normal range. She was treated with high-dose oral steroids with resolution of her symptoms. Her pain returned at the conclusion of the steroid taper, and it was controlled with chronic subcutaneous methotrexate and adalimumab injections.

Clinical and Optical Coherence Tomography Comparison Between Ocular Surface Squamous Neoplasia and Squamous Metaplasia.

PURPOSE: The purpose of this study was to compare the clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal squamous metaplasia and ocular surface squamous neoplasia (OSSN). METHODS: A retrospective case-control study of 8 patients, 4 with histologically confirmed squamous metaplasia and 4 with histologically confirmed OSSN, who presented to the Miami Veterans Administration Medical Center and Bascom Palmer Eye Institute between 2016 and 2020 was performed. Clinical characteristics, HR-OCT findings, and pathology were evaluated and compared. RESULTS: Four patients with squamous metaplasia and 4 with OSSN were evaluated. In the metaplasia group, 75% were male, 2 were White, and 2 were Black. In the OSSN group, all 4 were White males. All lesions were opalescent and occurred at the limbus; however, the borders were more smooth and rounded in the metaplastic lesions compared with OSSN. HR-OCT findings were indistinguishable between the 2 groups. CONCLUSIONS: There is overlap in clinical characteristics and HR-OCT findings between corneal squamous metaplasia and OSSN, highlighting one limitation of HR-OCT. As such, if a corneal opacity has some but not all HR-OCT findings of OSSN, squamous metaplasia should also be considered. A biopsy may be indicated to further evaluate and guide treatment.

Anterior segment optical coherence tomography characteristics of conjunctival papilloma as compared to papilliform ocular surface squamous neoplasia.

PURPOSE: To describe the anterior segment optical coherence tomography (AS-OCT) appearance of conjunctival papilloma and identify differentiating features from papilliform ocular surface squamous neoplasia (OSSN). METHOD: A retrospective chart review of individuals clinically diagnosed with conjunctival papilloma (n = 10) or papilliform OSSN (n = 10) based on slit lamp features. Data on demographics, tumour characteristics, and primary treatment were collected. AS-OCT features were assessed including epithelial thickness and reflectivity, a corrugated epithelial surface, presence of an overhanging edge, presence of intrinsic spaces and posterior shadowing. Histopathology was available in 5 papilloma and 3 OSSN specimens. RESULT: Overall, the majority of individuals in both groups were white males. OSSN lesions were more likely to involve the limbus (80% vs.10%, p = 0.005) and the bulbar conjunctiva (100% vs. 20%, p < 0.001) compared to papillomas. On AS-OCT, maximum epithelial thickness was thicker in papilloma compared to OSSN (936 ± 533 vs. 637 ± 207 µm, p = 0.009). The feature that best differentiated papilloma from OSSN was an overhanging edge (100% vs. 0%, p < 0.001), where the epithelial lesion was seen on top of underlying normal epithelium. Other features more common in papilloma compared to OSSN included a corrugated epithelial surface (70% vs.10%, p = 0.02), the presence of intrinsic spaces (100% vs. 50%, p = 0.03), and posterior shadowing (100% vs. 40%, p = 0.01). CONCLUSION: AS-OCT shows differentiating features between papilloma and OSSN with an overhanging edge as a distinctive AS-OCT feature of papilloma.

Genital self-amputation-its psychological urge.

Genital self-mutilation (GSM) is a rare phenomenon that can occur in patients with severe mental health illness. This case report highlights a rare case of self-inflicted bilateral testicular amputation and partial penile amputation in a patient who is a transwoman with a psychiatric history. The patient initially presented to urology in extremis with bilateral testicular amputation. The patient was resuscitated but required emergency surgery in the form of bilateral inguinal approach to ligate the cord and control haemostasis. The testes were not re-implanted as the patient refused and, after psychiatric discussion, was deemed to have capacity. She then re-presented within a week with self-inflicted partial amputation of penis. On both admissions, the patient had psychiatric evaluation but she was sectioned under the mental health act the second time. This case demonstrates how one can control haemostasis in the emergency scenarios of GSM and emphasizes the importance of psychiatric illness and evaluation in patients presenting with GSM.

Dendritic Mechanisms for In Vivo Neural Computations and Behavior.

Dendrites receive the vast majority of a single neuron's inputs, and coordinate the transformation of these signals into neuronal output. Ex vivo and theoretical evidence has shown that dendrites possess powerful processing capabilities, yet little is known about how these mechanisms are engaged in the intact brain or how they influence circuit dynamics. New experimental and computational technologies have led to a surge in interest to unravel and harness their computational potential. This review highlights recent and emerging work that combines established and cutting-edge technologies to identify the role of dendrites in brain function. We discuss active dendritic mediation of sensory perception and learning in neocortical and hippocampal pyramidal neurons. Complementing these physiological findings, we present theoretical work that provides new insights into the underlying computations of single neurons and networks by using biologically plausible implementations of dendritic processes. Finally, we present a novel brain-computer interface task, which assays somatodendritic coupling to study the mechanisms of biological credit assignment. Together, these findings present exciting progress in understanding how dendrites are critical for in vivo learning and behavior, and highlight how subcellular processes can contribute to our understanding of both biological and artificial neural computation.

Evolving discourses of COVID-19 and implications for medical education: a critical discourse analysis.

Background: The othering of individuals has been identified as a concern during the COVID-19 pandemic. The purpose of this study was to examine public commentary during early stages of the pandemic for: 1) emerging discourses that highlighted population-level inequities, and 2) the implications these discourses may have for medical education. Methods: Using a critical discourse analysis (CDA) approach, an archive of texts available in the public domain discussing COVID-19 was iteratively created, reviewed, and coded. We used an intersectional framework to analyze how COVID-19 highlighted structural and institutional inequity at the population level. Results: We found 86 representative texts published from March to June 2020. We focused our analysis on implications within Ontario. The two major discourses that emerged were "COVID-19 as Equalizer" and "COVID-19 as Discriminator." The former emerged in the early stages of the pandemic to mobilize public health recommendations and describe near-universal impacts on the public. The latter followed to highlight new and pre-existing forms of marginalization exacerbated by the pandemic. Conclusions: This study provides a unique perspective on how structural and systemic responses to COVID-19 were shaped through analysis of public discourse, and therefore, has implications for how the COVID-19 pandemic and future pandemics are framed for future medical learners.

Contexte: L'altérisation a été soulevée comme effet préoccupant de la pandémie de la COVID-19. L'objectif de cette étude était d'examiner les réactions du public au cours des premiers stades de la pandémie afin de dégager : 1) les discours émergents témoignant d'inégalités au sein de la population, et 2) les incidences potentielles de ces discours sur l'éducation médicale. Méthodes: L'approche adoptée est celle de l'analyse critique du discours (ACD). Nous avons constitué une archive de textes du domaine public contenant des commentaires relatifs à la COVID-19, que nous avons examinés, codés de manière itérative et analysés transversalement pour déceler dans quelle mesure la pandémie a mis en évidence les inégalités structurelles et institutionnelles au sein de la population. Résultats: Nous avons trouvé 86 textes représentatifs publiés entre mars et juin 2020. Nous avons concentré notre analyse sur les incidences en Ontario. Les deux principaux discours qui ont émergé sont «la COVID-19 comme facteur égalisateur¼ et «la COVID-19 comme facteur discriminant¼. Le premier est apparu au début de la pandémie pour inciter au respect des recommandations de santé publique et pour décrire les effets quasi universels sur la population. Il a été suivi par un second discours, mettant en lumière les formes nouvelles et préexistantes de marginalisation exacerbées par la pandémie. Conclusions: Cette étude offre une perspective unique de la pandémie telle qu'elle est perçue par le biais d'une analyse du domaine public. Elle peut donc éclairer la manière de présenter la gestion des pandémies aux futurs apprenants en médecine.

Chronic anophthalmic socket pain in the setting of deep orbital pseudocysts.

An 89-year-old woman presented with chronic pain and foreign body sensation in a healthy-appearing anophthalmic socket. Computed tomography of the orbits showed hyperdense, cystic lesions superior and posterior to the orbital implant. Orbital exploration was performed; the orbital implant and lesions were removed. Histopathology revealed cystic structures composed of fibrocellular tissue lined with histiocytes and multinucleated giant cells, consistent with pseudocysts. Postoperatively, the patient noted the resolution of her symptoms. While the etiology of the pseudocysts remains unclear, we hypothesize that the answer can be traced back to the original surgery. The cysts may have formed after extravasation of fluid or proteinaceous material from the eye, from glycerin on the donor sclera, or after introduction of foreign material during retrobulbar injection of local anesthesia. This is the first report of pseudocysts occurring in the orbit posterior to an implant.

Retinal dystrophies: A look beyond the eyes.

Purpose: To illustrate the importance of systemic evaluation in retinal dystrophies through examples of Alstrom syndrome, Bardet Biedl syndrome, and Refsum disease. Observations: Detailed eye evaluations, including visual acuity, visual field, slit lamp examination, and indirect ophthalmoscopy were performed. Retinal imaging included fundus photography and spectral domain optical coherence tomography (SD-OCT). Functional testing of the retina was done using full field electroretinography (ffERG). In addition, molecular genetic testing was performed using a ciliopathy panel, a retinal dystrophy panel, and whole genome sequencing (WGS).We report three individuals who presented with vision concerns first to ophthalmology, noted to have retinal dystrophy, and then referred to genomic medicine for genetic testing. Additional evaluation led to suspicion of specific groups of systemic disorders and guided appropriate genetic testing. The first individual presented with retinal dystrophy, obesity, and short stature with no reported neurocognitive deficits. Genetic testing included a ciliopathy panel that was negative followed by WGS that identified biallelic variants in ALMS: a novel frame-shift pathogenic variant c.6525dupT (p.Gln2176Serfs*17) and a rare nonsense pathogenic variant c.2035C > T (p.Arg679Ter) consistent with Alstrom syndrome. The second individual presented with retinal dystrophy, central obesity, and mild neurocognitive deficits. A ciliopathy genetic testing panel identified a homozygous pathogenic variant in BBS7: c.389_390del (p.Asn130Thrfs*4), confirming the diagnosis of Bardet Biedl syndrome. The third individual presented with progressive vision loss due to retinitis pigmentosa, anosmia, hearing loss, and shortened metatarsals and digits. Genetic testing identified two variants in PHYH: c.375_375del (p.Glu126Argfs*2) a pathogenic variant and c.536A > G (p.His179Arg), a variant of uncertain significance (VUS), suggestive of Refsum disease. Additional biochemical testing revealed markedly elevated phytanic acid with a low concentration of pristanic acid and normal concentrations of very long-chain fatty acids (C22:0, C24:0, C26:0), a pattern consistent with a diagnosis of Refsum disease. Conclusions and importance: In individuals who present with retinal dystrophy to ophthalmologists, additional systemic manifestations such as sensorineural hearing loss, anosmia, or polydactyly, should be sought and a positive history or examination finding should prompt an immediate referral to a clinical geneticist for additional evaluation and appropriate genetic testing. This facilitates pre-test genetic counseling and allows for more accurate diagnosis, prognosis, and management of affected individuals along with better recurrence risk estimates for family members. Identification of an underlying etiology also enhances the understanding of the pathophysiology of disease and expands the genotypic and phenotypic spectrum. Ultimately, successful recognition of these diseases facilitates development of targeted therapies and surveillance of affected individuals.

Squamoid Eccrine Ductal Carcinoma of the Eyelid: Clinicopathologic Correlation of a Case.

Squamoid eccrine ductal carcinoma (SEDC) is a rare cutaneous neoplasm that often manifests as a plaque or nodule in sun-exposed areas of older patients. Herein, the authors report the first case of SEDC in the eyelid. A 76-year-old man presented with a 2.5 × 1.5 mm area of left upper eyelid erythema, thickening, ulceration, and scaling with madarosis superotemporally just above the lash line. Full-thickness wedge biopsy demonstrated irregular epithelial tubules with nuclear atypia and focal squamous differentiation, consistent with SEDC. The patient underwent Mohs resection and has had no recurrence approximately 27 months after surgical removal. The authors present this case to raise awareness of SEDC to ophthalmologists as all previous cases have been described in the nonophthalmic literature. A full-thickness biopsy is recommended to avoid misdiagnosing SEDC as squamous cell carcinoma (SCC), a less aggressive tumor. With greater awareness, there may be increased recognition of this likely underreported, more malignant entity.

The use of high resolution optical coherence tomography (HR-OCT) in the diagnosis of ocular surface masqueraders.

INTRODUCTION: Ocular surface masqueraders encompass any ocular surface lesion masquerading as another ocular surface lesion. High resolution optical coherence tomography (HR-OCT) has emerged as an adjunctive tool to clinical acumen. This study's purpose is to evaluate the utility of HR-OCT images in guiding the diagnosis and management of those lesions. MATERIAL AND METHODS: 22 individuals with a clinically ambiguous ocular surface lesion with slit lamp photographs (SLP), HR-OCT images, and histopathological examination were included in the study. The presumptive clinical diagnosis based on SLP was compared to the diagnosis suggested by HR-OCT findings and to definitive diagnosis by histopathology. The main outcome of this study was the frequency in which HR-OCT findings guided the clinician to the correct diagnosis. RESULTS: 7 lesions were epithelial, 3 had an epithelial and a subepithelial component, and 12 were subepithelial. HR-OCT was most effective in discerning lesion location, successfully identifying the location in 100% of cases. Classic HR-OCT findings were detected in 68.2% of cases while suggestive features were detected in 31.8% of cases. The epithelial lesions' mean epithelial thickness was 265.4 ± 140.6 µm, the subepithelial lesions' mean was 58.0 ± 25.0 µm, and the combined lesions' mean was 140.0 ± 70.0 µm. The epithelium was significantly thicker in epithelial lesions compared to subepithelial and combined lesions. By ROC analysis we identified that using a cut off of 156 µm, the sensitivity was 86% and the specificity was 93%. DISCUSSION: HR-OCT can be a valuable diagnostic tool, assisting in the differentiation of ambiguous ocular surface pathologies by providing a cross-sectional, morphological image of the lesion.