Abstract Papillary thyroid cancer (PTC) is the most common endocrine malignancy, with incidence rising by approximately 3% each year. PTC disproportionately affects females of reproductive age, while male patients often exhibit more aggressive disease. Although overall survival is high, recurrence and metastasis remain significant clinical challenges that can persist for decades after initial diagnosis. Identifying reliable prognostic biomarkers and actionable therapeutic targets is therefore essential. Long non-coding RNAs (lncRNAs), a class of regulatory molecules with diverse roles in gene expression, display tissue- and cancer-specific expression patterns, making them promising candidates for biomarker discovery. Bioinformatic analysis of our PTC vs. normal thyroid genomic repository identified the lncRNA LINC01614 transcript as significantly 12-fold upregulated in PTC. Thus, we are studying LINC01614 as a potential PTC biomarker and/or therapeutic target. LINC01614 expression was found to be upregulated in multiple thyroid cancer cell lines. The PTC cell line K1 (∼2 fold upregulated; BRAFV600E; male), was selected for in vitro study. CRISPR interference (CRISPRi) was used to transcriptionally repress LINC01614 in K1 cells. LINC01614 knockdown in K1 resulted in decreased migration (∼20%), clonogenicity (∼34%) and proliferation (∼45%), indicating a role of this lncRNA in supporting malignant phenotypes. RNA sequencing analysis of a CRISPRi knockdown cell line vs. a CRISPRi control demonstrated reduced expression of key ferroptosis-related genes- SLC7A11 and SLC3A2. Both genes encode for the xCT system (cystine/glutamate reverse transporter) that regulates the uptake of cystine - a key precursor for glutathione (GSH) synthesis. GSH is a critical antioxidant defense against lipid peroxidation, further preventing ferroptosis. Thus, these findings suggested LINC01614 involvement in a ferroptosis-related mechanism. Consistent with this, total cell iron levels were quantified and found to be significantly higher in our LINC01614 knockdowns, signifying increased ferroptosis induction. Western blot analyses also showed decreased levels of ferroptosis-associated proteins such as GPX4, an important antioxidant enzyme that reduces lipid peroxidation to prevent ferroptosis. Current studies are ongoing to identify a LINC01614 mechanism of action within the ferroptosis pathway. These findings suggest that LINC01614 contributes to PTC pathogenesis through modulation of ferroptosis-related processes, highlighting its potential utility as a biomarker and/or therapeutic target. Citation Format: Danielle Quaranto, Michelle Carnazza, Nicole R. DeSouza, Sina Dadafarin, Augustine Moscatello, Humayun K. Islam, Codrin Iacob, Raj K. Tiwari, Jan Geliebter. Long non-coding RNA LINC01614 overexpression defines a ferroptosis-associated molecular signature in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5894.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy and is increasing annually in incidence by about 3%. PTC has a significantly higher prevalence in females of childbearing age and aggressiveness increases among males. Despite a high survival rate, disease recurrence and metastasis remain prominent issues-even decades after diagnosis. Therefore, the identification of prognostic biomarkers and actionable therapeutic targets remains a critical need. A newer class of epigenetic and regulatory molecules, known as long non-coding RNAs (lncRNAs), have demonstrated differential expression patterns in a variety of cancer types. lncRNAs modulate gene expression and drive carcinogenic behavior- making them attractive biomarkers and/or therapeutic targets for investigation. Bioinformatic analysis of our PTC vs. normal thyroid genomic repository identified the lncRNA LINC01614 transcript as significantly 12-fold upregulated in PTC. Thus, we are studying LINC01614 as a potential PTC biomarker. LINC01614 was found to be upregulated in thyroid cancer cell lines. Two PTC cell lines, TPC1 (∼5 fold upregulated; RET/PTC rearrangement; female) and K1 (∼2 fold upregulated; BRAFV600E; male), were selected for in vitro study. For phenotypic evaluation, CRISPRi technique was employed to achieve transcriptional repression of LINC01614 in TPC1and K1. LINC01614 knockdown in TPC1 and K1 resulted in decreased migration (∼20%), clonogenicity (∼50% and ∼34%, respectively), and proliferation (∼55% and ∼45%, respectively). RNA sequencing analysis of CRISPRi knockdown cell lines vs. CRISPRi controls demonstrated reduced expression of key ferroptosis-related genes- SLC7A11 and SLC3A2. Both genes encode for the xCT system (cystine/glutamate reverse transporter) that regulates the uptake of cystine - a key precursor for glutathione (GSH) synthesis. GSH is a critical antioxidant defense against lipid peroxidation, further preventing ferroptosis. Total cell iron levels were quantified and found to be significantly higher in our LINC01614 knockdowns, signifying increased ferroptosis induction. Studies are currently underway to identify the impact of LINC01614 on lipid peroxidation levels, reactive oxygen species production, as well as identification of ferroptosis-related protein expression in our PTC in vitro model. Elucidation of LINC01614’s carcinogenic mechanism of action through ferroptosis regulation is a promising and novel avenue of exploration for PTC prognosis and therapy. Danielle Quaranto, Michelle Carnazza, Nicole R. DeSouza, Sina Dadafarin, Augustine Moscatello, Humayun K. Islam, Codrin Iacob, Raj K. Tiwari, Jan Geliebter. Long non-coding RNA LINC01614 regulates ferroptosis-mediated carcinogenic phenotypes in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2804.

Chronic scleritis poses a diagnostic and therapeutic challenge with multiple mimickers, underlying autoimmune conditions, diverse presentations and variable course. Treatment for mild forms includes topical corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). For long-term control in patients with inadequate responses to steroids and NSAIDs, immunomodulators are employed. While oral cyclosporine has been used for inflammatory ocular conditions, research on topical cyclosporine for scleritis is limited. We present two cases: a man in his early 60s and a women in her late 20s, both with chronic, bilateral, intrapalpebral nodular scleritis with the clinical appearance of an inflamed pinguecula. After an initial poor response to conventional treatments, both patients responded positively to cyclosporine 0.05% ophthalmic emulsion as long-term monotherapy, likely due to cyclosporine's inhibitory effects. These outcomes suggest topical cyclosporine as an effective additive therapy to steroids to maintain quiescence for this particular subset of nodular scleritis, especially when traditional therapies are inadequate.

Constitutive secretion of VEGF is crucial for maintaining ocular circulation while hypoxia-induced VEGF secretion plays an important role in pathological neovascularization. Previous studies have highlighted the critical function of RPE cells in these situations. The role of uveal melanocytes (UM) in VEGF production, however, has not been well described. The aim of this study was to compare VEGF production from human RPE and UM cell lines obtained in pairs from 3 donors to minimize individual variability in cellular function. Cells were subjected to hypoxia, (1% oxygen environment) or chemical hypoxia (cobalt chloride, CoCl2) at different times or dosages, respectively. The effects of these treatments on the cell viability and cell proliferation were tested using MTT and cell counting with trypan blue testing. The production of VEGF and its main upstream factor (hypoxia-inducible factors-1α, HIF-1α) were measured in the conditioned culture medium and cellular extracts, by using ELISA analysis. Additionally, mRNA levels of VEGF and HIF-1α were quantified through real-time PCR analysis. The effects of CoCl2 on the expression of VEGF and HIF-1α in UM and RPE cells were also examined using flow cytometry. Hypoxia and COCL2 exposure did not affect cell viability and cell proliferation. This study revealed that the constitutive production of VEGF by RPE cells is significantly greater than from the UM. However, UM demonstrated a more robust response to high hypoxia or chemical hypoxic stimulation compared to RPE cells. The data suggests that while RPE cells play a critical role in constitutive VEGF production under normal conditions, UM may contribute significantly to the pathological increase in VEGF under severe ocular hypoxia. The observation that intraocular injection of CoCl2 to produce local chemical hypoxia, results in a significant increase of VEGF levels in intraocular fluids and tissues, has not been reported previously. While this model cannot currently test the in vitro results, it may help further our understanding of UM and RPE cells' roles in VEGF production in future studies using more advanced technologies in a well-established in vivo model.

PURPOSE:To report the association of Pseudofilariasis as a presenting sign of Alkaptonuria. METHOD:Case Report. RESULTS:A 49-year-old Indian man was referred because of wormlike objects in his left conjunctiva. Ocular and family history was non-contributory. He had not been to India in 15 years. Past medical history revealed hypertension, hypercholesterolemia, arthritis, and a myocardial infarct. He had undergone two stents, bilateral Achilles tendon repairs and bilateral knee replacements. ROS showed longstanding back stiffness and pain. On ocular examination the vision was 20/25 in each eye and positive findings were in the left eye bulbar conjunctival which showed stationary black vermiform (filarial in appearance) foreign bodies along with 2 small corneal limbal pigmented deposits. Conjunctival biopsy showed dilated lymph channels with interstitial proteinaceous material of a light brown color consistent with Ochronotic pigment; hence diagnostic of Alkaptonuria. CONCLUSIONS:Pseudofilariasis may be a presenting sign of Alkaptonuria and occur years before a clinical diagnosis is made. Filariasis is always involves white worms and never black. Knowing the ophthalmic signs of this rare disease may lead to an accurate diagnosis earlier thusly avoiding unnecessary tests and examinations.

INTRODUCTION:Melanotic schwannoma (MS) is a rare neoplasm composed of Schwann cells with melanosomes in various maturation stages. While MS is typically observed in spinal nerve roots or peripheral nerves, their involvement in intraocular structures is uncommon. Here, we present a case of spontaneous globe rupture as the presenting feature of intraocular extension of a MS. METHODS:Enucleation was performed to remove the lesion. Confirmatory light microscopy and immunohistochemistry were used to properly diagnose and differentiate from conventional schwannoma and uveal malignant melanoma. RESULTS:The ocular tumor in our patient showed melanin pigmentation with positive melanocytic markers. The tumor revealed spindle and epithelioid cells proliferating in fascicles, which has previously been described for MS. No choroidal invasion, moderate nuclear pleomorphism, and a low mitotic rate were observed supporting a diagnosis of MS in our patient. CONCLUSION:With reports of MS with high recurrence and metastatic spread rates, there have been some suggestions that MS should be considered an aggressive malignancy. This case highlights a dramatic presentation of a rare ocular malignancy with some features of aggressiveness. Our case report endorses the importance of close monitoring for local recurrence or metastasis to prevent a poor outcome.

ObjectiveTo describe the management of patients with occult anterior uveal melanomas presenting with extrascleral extension.Methods and analysisRetrospective case series including five patients with small pigmented nodular mass on the episclera. Each lesion was documented by slit-lamp photography and measured with high-frequency ultrasound imaging (ultrasound biomicroscopy). Diagnosis of uveal melanoma was confirmed by biopsy with lamellar sclerectomy. Immediate scleral patch graft repair was performed. Later, each tumour was treated with palladium-103 ophthalmic plaque brachytherapy. The mean plaque diameter was 12 mm (median, 12; range, 10–14). A mean apex prescription dose of 87 Gy (median, 84.5; range, 82.3–99.2) to a tumour depth of 2 mm from the inner sclera delivered over 7 continuous days. The main outcome measures were best-corrected visual acuity, changes in tumour and scleral characteristics and complications.ResultsDuring each surgery, residual tumour was visualised within an emissary passageway at the deep plane of scleral resection. At a mean of 80 months (median, 57; range, 24–159) follow-up, no patients experienced graft infection, scleromalacia or rejection. Biopsy was required to establish the diagnosis, transillumination failed, and therefore ultrasound measurements were used to determine the plaque size required to treat the relatively occult intraocular component. Despite these challenges, there were no cases of local tumour recurrence, secondary enucleation or metastatic disease. Attributed to cataract surgery, visual acuities improved in three patients and two were stable.ConclusionExtrascleral uveal melanoma extension can occur with undetectable, occult intraocular tumours. In these cases, plaque radiation effectively induced local tumour control, preserved vision and prevented metastasis.

Pam3CSK4 activates Toll-like receptors 2 and 1 (TLR1/2), which recognize mainly molecules from gram-positive pathogens. The effect of Pam3CSK4 on various cytokine and chemokine expression in cultured human uveal melanocytes (UM) has not been studied systematically. The purpose of this study was to investigate the mechanistic expressions of seven cytokines and chemokines of interleukin- (IL-) 6, IL-10, MCP-1 (CCL-2), CXCL-1 (GRO-α), CXCL-8 (IL-8), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) in UM. These cytokines are reported to be increased in intraocular fluids or tissues of the patients with endophthalmitis and non-infectious uveitis, as well as in various experimental animal uveitic models in the literature. Flow cytometry was used to measure the effects of Pam3CSK4 on the expression of TLR1/2 in UM. ELISA and Real-time PCR analysis were used to estimate the ability of Pam3CSK4 to elevate these cytokines and chemokines levels in conditioned media and cell lysates of UM, respectively. Flow cytometry measured and compared the phosphorylated MAPK pathway and activated NF-κB signals pathway in UM, treated with and without Pam3CSK4. ELISA analysis tested the effect of various signal inhibitors (ERK1/2, JNK1/2, p38 and NF-κB) on Pam3CSK4-induced IL-6 levels in cultured UM. The role of TLR2 in Pam3CSK4-induced acute anterior uveitis in experimental mouse model was tested in TLR2 knockout (TLR2 KO) mice and their wild-type C57Bl/6 controls. Pam3CSK4 increased the expression of TLR1/2 proteins in cultured UM. Pam3CSK4 significantly elevated the IL-6, MCP-1, CXCL-1, CXCL-8 protein, and mRNA levels in cultured UM, but not IL-10, TNF-α, or IFN-γ. Pam3CSK4 activated NF-κB, ERK, JNK, and p38 expression. Pam3CSK4-induced expression of IL-6 was decreased by NF-κB, ERK, INK, and p38 inhibitors; especially the NF-κB inhibitor, which can completely block the IL-6 stimulation. Intravitreal injection of Pam3CSK4 induced acute anterior uveitis in C57Bl/6 mice, this effect was significantly reduced in TLR2 KO mice. TLR1/2 plays an important role against invading pathogens, especially gram-positive bacteria; but an excessive reaction to molecules from gram-positive bacteria may promote non-infectious uveitis. UM can produce IL-6, MCP-1, CXCL-1, and CXCL-8, and are one of the target cells of TNF-α and IFN-γ. TLR-2 inhibitors might have a beneficial effect in the treatment of certain types of uveitis and other ocular inflammatory-related diseases and warrant further investigation.

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.

Abstract Ligneous conjunctivitis is a rare cause of chronic conjunctivitis that may be triggered by ocular insults such as trauma or infections. We present an interesting case of ligneous conjunctivitis caused by a viral infection that responded well to conservative management. Topical cyclosporine and heparin are a good treatment regimen that caused resolution of lesions and prevented recurrences.

Fibroblast-stimulating lipopeptide (FSL-1) can activate Toll-like receptor 2 and 6 (TLR2/6), which recognize relevant molecules from gram-positive pathogens, fungus, and mycoplasma, and elevates the expression of CXCL1 and CXCL2, neutrophil chemoattractants, in certain types of cells. This effect has not previously been reported in the uveal melanocytes (UM). This study was designed to test the hypothesis that FSL-1 can induce the expression and secretion of CXCL1 and CXCL2 via activation of TLR2/6 in cultured human UM and producing an acute non-infectious uveitis reaction in the mouse. Flow cytometry and fluorescent immunostaining were used to measure the effect of FSL-1 on the expression of TLR2/6 in UM. Real time PCR and ELISA analysis were used to assess the ability of FSL-1 to elevate CXCL1/CXCL2 levels in cell lysates and conditioned media of UM, respectively. Flow cytometry measured phosphorylated MAPK and activated NF-κB signals in UM, with and without FSL-1 treatment. ELISA analysis tested the impact of various signal inhibitors (NF-κB, p38 MAPK, JNK1/2 and ERK1/2) and TLR2/6 antagonists on FSL-1-induced CXCL1/CXCL2 levels in cultured UM. The effects of neutralizing antibodies to TLR2 on FSL-1-induced mouse uveitis were tested in an experimental animal model. FSL-1 induced the expression of TLR2/6 proteins in cultured UM. FSL-1 significantly elevated the CXCL1 and CXCL2 proteins and mRNA levels in cultured UM time- and dose-dependently. FSL-1 mainly activated NF-κB, JNK, and expression of TLR2. FSL-1-induced expression of CXCL1 and CXCL2 was blocked by NF-κB, JNK, ERK inhibitors and TLR2 antagonists. Intravitreal injection of FSL-1 induced acute non-infectious mouse uveitis, which was significantly reduced in severity by a TLR2 antagonist. These results suggest that UM may play a role in the immune reaction, which targets invading pathogens, especially gram-positive bacteria. On the other hand, an excessive reaction to molecules from gram-positive bacteria may promote an inflammatory state of non-infectious uveitis.

Purpose: To present a case of tattoo side effects not limited to the tattoo site and rise an alarm regarding using non-FDA-approved products. Observations: A 30-year-old female presented with bilateral ocular pain, dryness, and itching. The ocular exam showed bilateral injection and edema of the superior palpebral and bulbar conjunctiva. Several 1–2 mm dark pigmented lesions and papillae coursing along the upper palpebral conjunctival lid margin and 5 mm above the margin were found in both eyes. The ocular surface was dry with diffuse superficial punctate keratitis. The biopsy report showed granular foreign material in the dermis. SOX-10 and MART-1 immunostaining highlighted melanocyte distribution and the sample was diagnosed as exogenous pigment consistent with tattoo ink by the pathologist. On further investigation following the pathology report, the patient stated that she got bilateral permanent eyebrow tattoos 4 months before presentation in a country other than the United States, and she was not aware about the standards of the ink used, nor the certification of the person performing the tattoo. The patient denied any type of tattoo or manipulation on the eyes or orbit, including sclera or conjunctivae. Conclusions: Importance: The complications of periorbital tattooing are not limited to the point tattoo location and can potentially spread to the nearby segments. It is notable that there is no FDA approved tattoo ink available, even with a certified tattoo artist performing the tattoo, the risks of inflammation, infection, and other side effects are still present.

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen-mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2.7-fold reduction in AR expression (p < 0.005) in papillary thyroid cancer compared with matched, normal tissue. An in vitro cell model was developed by stably transfecting AR into 8505C undifferentiated thyroid cancer cells (resulting in clone 84E7). The addition of DHT to the clone 84E7 resulted in AR translocation into the nucleus and a 70% reduction in proliferation, with a shift in the cell cycle toward G1 arrest. RNASeq analysis revealed significant changes in mRNA levels associated with proliferation, cell cycle, and cell cycle regulation. Furthermore, androgen significantly decreased the levels of the G1-associated cell cycle progression proteins cdc25a CDK6 CDK4 and CDK2 as well as increased the levels of the cell cycle inhibitors, p27 and p21. The data strongly suggest that DHT induces a G1 arrest in androgen-responsive thyroid cancer cells. Together, these data support our hypothesis that AR/androgen may play a protective, antiproliferative role and are consistent with younger men having a lower incidence of thyroid cancer than women.

Objective: To perform micro-incision, trans-iridal, aspiration-cutter-assisted biopsy for ciliary body tumours. Design: Retrospective, nonrandomized, observational, interventional case series. Methods: Five consecutive patients undergoing ciliary body tumour biopsy were clinically diagnosed using slit-lamp photography, gonioscopy, high-frequency ultrasound imaging, and systemic radiographic staging. A 1-2 mm clear cornea incision was placed opposite to the central clock hour of the ciliary body tumour. Viscoelastic was infused into the anterior chamber for stabilization and endothelial protection. Then, a 27-gauge aspiration cutter was used to make an iridotomy at the iris root and then extend through the iris into the tumour. Biopsy was performed using mechanical cutting starting at 300 cuts per minute and aspiration at 600 mm Hg. After withdrawal of the cutter from the eye, the effluent tube was flushed into a 3 cc syringe, inspected for specimen under the operating microscope and sent for pathology. Multiple biopsies were performed on each patient. Viscoelastic was removed and Seidel examination of the corneal wound performed. Results: Five eyes were biopsied. A mean 3.6 passes were used to obtain tumour tissue. Tumour cells and tissue were obtained in all cases. Cytologic, histopathologic, and immuno-histochemical analysis were performed (100%, n = 5/5). Diagnoses included melanoma (60%, n = 3/5), melanocytoma (20%, n = 1/5), and leiomyoma (20%, n = 1/5). Transient postoperative hyphemas cleared within 1 week (80%, n = 4/5). No secondary glaucoma, infection, or cataracts were noted. Conclusion: Aspiration-cutter biopsy through the iris root provided a minimally invasive, safe method for obtaining ciliary body tissue for cytology, histopathology, and immunohistochemical analysis.

Keratomycosis or mycotic keratitis is recognized as one of the major causes of ophthalmic morbidity worldwide. The most common organisms linked to keratomycosis include Candida spp., Fusarium spp., and Aspergillus spp. However, varieties of saprobic fungi have been reported as causative agents of keratomycosis. Amongst these are members of the genus Colletotrichum. Herein we present the first reported case of C. chlorophyti infection in a post-corneal transplant patient, suggesting an increasing role for Colletotrichum species as emerging human pathogens, particularly in the transplant population.

Thyroid cancer is the most prevalent endocrine malignancy in the United States with greater than 53,000 new cases in 2020. There is a significant gender disparity in disease incidence as well, with women developing thyroid cancer three times more often than men; however, the underlying cause of this disparity is poorly understood. Using RNA-sequencing, we profiled the immune landscape of papillary thyroid cancer (PTC) and identified a significant inverse correlation between androgen receptor (AR) levels and the immune checkpoint molecule PD-L1. The expression of PD-L1 was then measured in an androgen responsive-thyroid cancer cell line. Dihydrotestosterone (DHT) treatment resulted in significant reduction in surface PD-L1 expression in a time and dose-dependent manner. To determine if androgen-mediated PD-L1 downregulation was AR-dependent, we treated cells with flutamide, a selective AR antagonist, and prior to DHT treatment to pharmacologically inhibit AR-induced signaling. This resulted in a > 90% restoration of cell surface PD-L1 expression, suggesting a potential role for AR activity in PD-L1 regulation. Investigation into the AR binding sites showed AR activation impacts NF-kB signaling by increasing IkBα and by possibly preventing NF-kB translocation into the nucleus, reducing PD-L1 promoter activation. This study provides evidence of sex-hormone mediated regulation of immune checkpoint molecules in vitro with potential ramification for immunotherapies.

BACKGROUND:Ciliary body tumors can remain undetected and achieve large dimensions. Pigmented ciliary body tumors include: melanoma, leiomyoma and melanocytoma, however correct diagnosis may require tissue diagnosis with immunohistochemical stains.CASE PRESENTATION:Two men presented with identical ciliochoroidal tumors. Both had darkly pigmented dome-shaped anterior uveal masses, exudative retinal detachments and transillumination shadowing. Ocular PET-CT imaging revealed that both were metabolically active consistent with a diagnosis of cancer. However, immunohistochemical examination revealed one a leiomyoma and the other melanoma.CONCLUSION:Uveal leiomyoma can be an indistinguishable doppelgänger to ciliochoroidal melanoma, where the diagnosis can only be established by immunohistopathology.

PURPOSE:To report an unusual case of endogenous panophthalmitis involving Candida auris and describe its clinical and histopathological features.FINDINGS:A 30 year-old man with history of human immunodeficiency virus, polysubstance abuse, syphilis, and recently treated pneumonia presented with polymicrobial endogenous panophthalmitis. Two separate ocular specimens confirmed simultaneous Pseudomonas aeruginosa and Candida auris involvement. Histopathological analysis demonstrated fulminant polymorphonuclear infiltration of all ocular tissue layers. Despite aggressive management including two intravitreal injections and enucleation, the patient died, ultimately after receiving care at four neighboring urban medical centers.CONCLUSIONS AND IMPORTANCE:Candida auris has been a recently and increasingly described pathogen leading to mortality in metropolitan hospitals worldwide. To the authors' knowledge, Candida auris has not previously been reported with endophthalmitis or panophthalmitis. Future cases may be expected with the reported rise in Candida auris. A high suspicion of its contribution to panophthalmitis could be warranted early in the evaluation and management of profoundly immunocompromised patients, particularly those who have had sequential care at multiple neighboring metropolitan hospitals.

Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, whereas iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high-frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. We found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment is governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.