ABSTRACT
PURPOSE: The purpose of this study was to assess the accuracy and completeness of 3 large language models (LLMs) to generate information about antibody-drug conjugate (ADC)-associated ocular toxicities. METHODS: There were 22 questions about ADCs, tisotumab vedotin, and mirvetuximab soravtansine that were developed and input into ChatGPT 4.0, Bard, and LLaMa. Answers were rated by 4 ocular toxicity experts using standardized 6-point Likert scales on accuracy and completeness. ANOVA tests were conducted for comparison between the 3 subgroups, followed by pairwise t-tests. Interrater variability was assessed with Fleiss kappa tests. RESULTS: The mean accuracy score was 4.62 (SD 0.89) for ChatGPT, 4.77 (SD 0.90) for Bard, and 4.41 (SD 1.09) for LLaMA. Both ChatGPT (P = 0.03) and Bard (P = 0.003) scored significantly better for accuracy when compared with LLaMA. The mean completeness score was 4.43 (SD 0.91) for ChatGPT, 4.57 (SD 0.93) for Bard, and 4.42 (SD 0.99) for LLaMA. There were no significant differences in completeness scores between groups. Fleiss kappa assessment for interrater variability was good (0.74) for accuracy and fair (0.31) for completeness. CONCLUSIONS: All 3 LLMs had relatively high accuracy and completeness ratings, showing LLMs are able to provide sufficient answers for niche topics of ophthalmology. Our results indicate that ChatGPT and Bard may be slightly better at providing more accurate answers than LLaMA. As further research and treatment plans are developed for ADC-associated ocular toxicities, these LLMs should be reassessed to see if they provide complete and accurate answers that remain in line with current medical knowledge.
ABSTRACT
BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.
Subject(s)
Retinal Neoplasms , Tomography, Optical Coherence , Uveitis , Vitreous Body , Humans , Tomography, Optical Coherence/methods , Retrospective Studies , Male , Female , Middle Aged , Retinal Neoplasms/diagnosis , Retinal Neoplasms/diagnostic imaging , Aged , Vitreous Body/pathology , Vitreous Body/diagnostic imaging , Uveitis/diagnosis , Adult , Intraocular Lymphoma/diagnosis , Visual Acuity , Diagnosis, Differential , Aged, 80 and overABSTRACT
Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.
ABSTRACT
BACKGROUND: While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology. METHODS: This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023. We randomly assigned 21 neuro-ophthalmology questions to 13 experts. Each expert provided an answer and then edited a ChatGPT-4-generated response, timing both tasks. In addition, 5 LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, Bard) generated responses. Anonymized and randomized responses from Expert + AI, human experts, and LLMs were evaluated by the remaining 12 experts. The main outcome was the mean score for quality and empathy, rated on a 1-5 scale. RESULTS: Significant differences existed between response types for both quality and empathy (P < 0.0001, P < 0.0001). For quality, Expert + AI (4.16 ± 0.81) performed the best, followed by GPT-4 (4.04 ± 0.92), GPT-3.5 (3.99 ± 0.87), Claude (3.6 ± 1.09), Expert (3.56 ± 1.01), Bard (3.5 ± 1.15), and Bing (3.04 ± 1.12). For empathy, Expert + AI (3.63 ± 0.87) had the highest score, followed by GPT-4 (3.6 ± 0.88), Bard (3.54 ± 0.89), GPT-3.5 (3.5 ± 0.83), Bing (3.27 ± 1.03), Expert (3.26 ± 1.08), and Claude (3.11 ± 0.78). For quality (P < 0.0001) and empathy (P = 0.002), Expert + AI performed better than Expert. Time taken for expert-created and expert-edited LLM responses was similar (P = 0.75). CONCLUSIONS: Expert-edited LLM responses had the highest expert-determined ratings of quality and empathy warranting further exploration of their potential benefits in clinical settings.
ABSTRACT
Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. Design: Randomized, masked multicenter study. Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy (P < 0.001, P < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality (P < 0.001) and empathy (P < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response (P = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content (P = 0.35), missing content (P = 0.001), extent of possible harm (P = 0.356), and likelihood of possible harm (P = 0.129). Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article.
ABSTRACT
BACKGROUND AND OBJECTIVE: The objective was to evaluate factors associated with clinical presentation of uveal melanoma (UM) during the initial two years of the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: This was a multi-site, retrospective cohort study of patients treated for uveal melanoma during the first (early) and second (late) year of the pandemic compared with the year prior (control). RESULTS: A total of 48, 67, and 75 patients were in the control, early, and late cohorts, respectively. The early cohort had a higher frequency of large tumors (control: 29.2%, early: 40.3%, late: 29.3%; P < 0.001) at presentation. Both the early and late cohorts had higher rates of enucleation (control: 8.33%, early: 20.9%, late: 18.67%; P ≤ 0.0338) compared to the control cohort. CONCLUSIONS: While there was an increase in large tumors along with a rise in enucleation during the first year of the pandemic, enucleation rates remained elevated even while tumor sizes normalized. [Ophthalmic Surg Lasers Imaging Retina 2024;55:278-284.].
Subject(s)
COVID-19 , Eye Enucleation , Melanoma , SARS-CoV-2 , Uveal Neoplasms , Humans , Melanoma/epidemiology , Melanoma/diagnosis , Uveal Neoplasms/epidemiology , Uveal Neoplasms/diagnosis , COVID-19/epidemiology , Retrospective Studies , Male , Female , Middle Aged , Aged , Pandemics , AdultABSTRACT
Angiogenesis has an essential role in the de novo evolution of choroidal melanoma as well as choroidal nevus transformation into melanoma. Differentiating early-stage melanoma from nevus is of high clinical importance; thus, imaging techniques that provide objective information regarding tumor microvasculature structures could aid accurate early detection. Herein, we investigated the feasibility of quantitative high-definition microvessel imaging (qHDMI) for differentiation of choroidal tumors in humans. This new ultrasound-based technique encompasses a series of morphological filtering and vessel enhancement techniques, enabling the visualization of tumor microvessels as small as 150 microns and extracting vessel morphological features as new tumor biomarkers. Distributional differences between the malignant melanomas and benign nevi were tested on 37 patients with choroidal tumors using a non-parametric Wilcoxon rank-sum test, and statistical significance was declared for biomarkers with p-values < 0.05. The ocular oncology diagnosis was choroidal melanoma (malignant) in 21 and choroidal nevus (benign) in 15 patients. The mean thickness of benign and malignant masses was 1.70 ± 0.40 mm and 3.81 ± 2.63 mm, respectively. Six HDMI biomarkers, including number of vessel segments (p = 0.003), number of branch points (p = 0.003), vessel density (p = 0.03), maximum tortuosity (p = 0.001), microvessel fractal dimension (p = 0.002), and maximum diameter (p = 0.003) exhibited significant distributional differences between the two groups. Contrast-free HDMI provided noninvasive imaging and quantification of microvessels of choroidal tumors. The results of this pilot study indicate the potential use of qHDMI as a complementary tool for characterization of small ocular tumors and early detection of choroidal melanoma.
ABSTRACT
BACKGROUND: Risk factors for small choroidal melanocytic lesion growth to melanoma have been redefined using multimodal imaging. We explored provider ability to recognize risk factors for small choroidal melanocytic lesion growth to melanoma before and after image-based education and with and without multimodal imaging. METHODS: Providers were invited to participate in a survey assessing ability to identify risk factors for small choroidal melanocytic lesion growth to melanoma using either fundus imaging or multimodal imaging. Risk factors included thickness >2 mm on ultrasonography, subretinal fluid on optical coherence tomography, presence of orange pigment by autofluorescence, acoustic hollowness by ultrasonography, and diameter >5 mm by fundus imaging. Performance was assessed before and after reviewing an educational PowerPoint providing pictorial examples of risk factors. Comparison between groups was conducted using two-tailed Fisher's exact test. RESULTS: Thirty and 26 providers completed the pre-education and post-education assessments, respectively. Post-education participants were more accurate within ±1 risk factor for lesions with zero risk factors (77% vs. 100%, p = 0.01) or two risk factors (79% vs. 91%, p = 0.03). Following education, participants presented with multimodal imaging more often correctly identified lesions with four (12% vs. 42%, p = 0.03) or five (4% vs. 39%, p = 0.004) risk factors, demonstrated lower mean level of concern for lesions with zero risk factors (2.0 vs. 1.4, p < 0.001), and expressed higher level of concern for lesions with 5 risk factors (2.4 vs. 3.6, p < 0.001). CONCLUSION: Use of multimodal imaging may be more beneficial than education itself to improve accuracy of risk factor identification for small choroidal melanocytic lesions.
Subject(s)
Choroid Neoplasms , Melanoma , Humans , Melanoma/diagnostic imaging , Melanoma/pathology , Choroid Neoplasms/diagnostic imaging , Choroid Neoplasms/pathology , Retrospective Studies , Tomography, Optical Coherence/methods , Multimodal Imaging/methods , Risk FactorsABSTRACT
OBJECTIVE: To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. DESIGN: Single-center retrospective study. PARTICIPANTS: Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. RESULTS: Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 µm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. CONCLUSION: Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.
Subject(s)
Choroid Neoplasms , Macular Edema , Melanoma , Uveal Neoplasms , Humans , Retrospective Studies , Vascular Endothelial Growth Factor A , Melanoma/diagnosis , Melanoma/radiotherapy , Macular Edema/drug therapy , Choroid Neoplasms/diagnosis , Choroid Neoplasms/radiotherapy , Visual Acuity , Intravitreal Injections , Angiogenesis Inhibitors , Tomography, Optical CoherenceSubject(s)
Adenocarcinoma , Choroid Neoplasms , Humans , Choroid/pathology , Choroid Neoplasms/pathology , Neoplasm InvasivenessSubject(s)
Antigens, Neoplasm , Biomarkers, Tumor , Eye Enucleation , Gene Expression Profiling , Immunohistochemistry , Melanoma , Uveal Neoplasms , Humans , Uveal Neoplasms/genetics , Uveal Neoplasms/metabolism , Melanoma/genetics , Melanoma/metabolism , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Profiling/methods , Male , Female , Gene Expression Regulation, Neoplastic , Middle Aged , AgedABSTRACT
Introduction: The aim of this study was to determine the predictive value of International Classification of Diseases, 9th Revision (ICD-9) billing codes for identifying ocular oncology diagnoses. Methods: Population-based retrospective cohort study of all Olmsted County, Minnesota residents with any ocular neoplasm-related ICD-9 code from January 1, 2006 to October 1, 2015. All medical records were reviewed for confirmation of ocular neoplasm. Diagnoses with ≥5 cases confirmed via a medical record review were compared to corresponding ICD-9 codes. Main outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-9 codes. Results: Among 3,932 subjects with ≥1 ocular neoplasm-related ICD-9 code, 21 diagnoses met study criteria. The most frequent intraocular, extraocular/orbital, and ocular surface diagnoses were choroidal nevus (n = 824), epidermal inclusion cyst (n = 263), and conjunctival nevus (n = 74), respectively. PPVs ranged from 1.2% to 73.8%, NPVs from 96.9% to 100%, sensitivity from 0% to 100%, and specificity from 85.7% to 100%. Among malignant neoplasms, PPV ranged from 0% to 73.8%: ocular surface squamous neoplasia (PPV: 0%), choroidal melanoma (PPV: 25.0%), eyelid squamous cell carcinoma (PPV: 46.7%), and eyelid basal cell carcinoma (PPV: 73.8%). Among benign neoplasms, PPV ranged from 1.2% (dermoid cyst) to 61.6% (choroidal nevus). Conclusion: There was a wide variation in a predictive value of ocular neoplasm-related ICD-9 billing codes, which suggests that ocular oncology-related claims data alone may overestimate the true number of ocular oncology diagnoses.
ABSTRACT
PURPOSE: To describe ocular involvement in subjects with Whipple's disease (WD). METHODS: Retrospective review of documented WD cases seen at Mayo Clinic between 1980 and 2021 with ocular involvement. RESULTS: Of 217 patients with WD, 30 had eye exams and four (two female, median age 58.5 years) had ocular involvement. Findings included anterior/intermediate uveitis (n = 2), intermediate uveitis and phlebitis (n = 1), and chorioretinitis with vitritis (n = 1). The diagnosis was confirmed by vitreous biopsy in three of four cases. In two cases, WD diagnosis was unconfirmed prior to the ocular diagnosis. Systemic manifestations included gastrointestinal symptoms in all patients, synovitis (n = 3), weight loss (n = 2), and pericarditis (n = 1). Mean time from onset of ocular symptoms to ocular diagnosis was 11 months (range 2-28 months). Prior systemic symptoms were present as long as 3 years. CONCLUSIONS: WD is uncommon and ocular involvement is even more rare. However, WD should be considered in the differential for all patients with chronic recalcitrant uveitis, especially in the setting of polyarthralgias and/or gastrointestinal symptoms. Vitreous biopsy is a reliable method to diagnose ocular WD.Abbreviations and Acronyms: Whipple's disease (WD), intestinal lipodystrophy (IL), polymerase-chain reaction (PCR), periodic acid-Schiff (PAS), trimethoprim/sulfamethoxazole (TMP/SMX).
ABSTRACT
PURPOSE: To investigate clinical manifestations and prognoses in pediatric patients (≤12 years old) with ocular melanoma. METHODS: This was a retrospective, multicenter cohort study with individual participant data (IPD) meta-analysis pooling available published cases, and unpublished cases from an international collaboration of seven ocular oncology centers. RESULTS: There were 133 eyes of 133 pediatric patients with choroidal or ciliary body (n = 66 [50%]), iris (n = 33 [25%]), conjunctival (n = 26 [19%]), and eyelid (n = 8 [6%]) melanoma. Overall, the mean patient age at presentation was 7 years (median, 8; range, 1-12 years), with 63 males (49%). The mean age by tumor site was 6.50 ± 3.90, 7.44 ± 3.57, 9.12 ± 2.61, and 5.63 ± 2.38 years, for choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively (P = 0.001). Association with ocular melanocytosis was seen in 15%, 11%, 4%, and 0%, respectively (P = 0.01). Frequency of ocular melanoma family history did not vary by tumor site (7%, 17%, 9% and 12%, resp. [P = 0.26]). After mean follow-up of 74, 85, 50, and 105 months (P = 0.65), metastasis was seen in 12%, 9%, 19%, and 13% of choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively. Death was reported in 5%, 3%, 8%, and 0%, respectively, with survival analysis indicating higher mortality in choroidal/ciliary body and conjunctival melanoma patients. CONCLUSIONS: Ocular melanoma in the pediatric population is rare, with unique clinical features and outcomes. Iris melanoma accounts for about one-third of pediatric uveal melanoma cases.
Subject(s)
Eye Neoplasms , Eyelid Neoplasms , Melanoma , Uveal Neoplasms , Male , Humans , Child , Melanoma/pathology , Retrospective Studies , Cohort Studies , Uveal Neoplasms/pathology , Uveal Neoplasms/secondary , Eye Neoplasms/complications , Multicenter Studies as TopicABSTRACT
To investigate downstream molecular changes caused by mitogen-activated protein kinase (MEK) inhibitor treatment and further explore the impact of direct knockdown of early growth response-1 ( EGR1 ) in melanoma cell culture. RNA-sequencing (RNA-Seq) was performed to determine gene expression changes with MEK inhibitor treatment. Treatment with MEK inhibitor (trametinib) was then assessed in two cutaneous (MEL888, MEL624) and one conjunctival (YUARGE 13-3064) melanoma cell line. Direct knockdown of EGR1 was accomplished using lentiviral vectors containing shRNA. Cell viability was measured using PrestoBlueHS Cell Viability Reagent. Total RNA and protein were assessed by qPCR and SimpleWestern. RNA-Seq demonstrated a profound reduction in EGR1 with MEK inhibitor treatment, prompting further study of melanoma cell lines. Following trametinib treatment of melanoma cells, viability was reduced in both cutaneous (MEL888 26%, P â <â 0.01; MEL624 27%, P â <â 0.001) and conjunctival (YUARGE 13-3064 33%, P â <â 0.01) melanoma compared with DMSO control, with confirmed EGR1 knockdown to 0.04-, 0.01-, and 0.16-fold DMSO-treated levels (all P â <â 0.05) in MEL888, MEL624, and YUARGE 13-3064, respectively. Targeted EGR1 knockdown using shRNA reduced viability in both cutaneous (MEL624 78%, P â =â 0.05) and conjunctival melanoma (YUARGE-13-3064 67%, P â =â 0.02). RNA-Sequencing in MEK inhibitor-treated cells identified EGR1 as a candidate effector molecule of interest. In a malignant melanoma cell population, MEK inhibition reduced viability in both cutaneous and conjunctival melanoma with a profound downstream reduction in EGR1 expression. Targeted knockdown of EGR1 reduced both cutaneous and conjunctival melanoma cell viability independent of MEK inhibition, suggesting a key role for EGR1 in melanoma pathobiology.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , Mitogens , Dimethyl Sulfoxide , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Extracellular Signal-Regulated MAP Kinases/metabolism , Protein Kinase Inhibitors/pharmacology , Mitogen-Activated Protein Kinase Kinases , RNA, Small Interfering , Cell Line, Tumor , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
Pigmented ocular fundus lesions can range from benign to malignant. While observation is reasonable for asymptomatic benign lesions, early recognition of tumours that are vision or life threatening is critical for long-term prognosis. With recent advances and increased accessibility of multimodal imaging, it is important that providers understand how to best use these tools to detect tumours that require early referral to subspecialty centres. This review aims to provide an overview of pigmented ocular fundus lesions and their defining characteristics using multimodal imaging. We cover the spectrum of pigmented ocular fundus lesions, including freckle and focal aggregates of normal or near-normal uveal melanocytes, retinal pigment epithelium (RPE) hyperplasia, congenital hypertrophy of the RPE, RPE hamartoma associated with familial adenomatous polyposis, congenital simple hamartoma of the RPE, combined hamartoma of the retina and RPE (congenital hypertrophy of the RPE), choroidal nevus, melanocytosis, melanocytoma, melanoma, adenoma, and RPE adenocarcinoma. We describe key diagnostic features using multimodal imaging modalities of ultra-widefield fundus photography, fundus autofluorescence, optical coherence tomography (OCT), enhanced-depth imaging OCT, ultrasonography, fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), with particular attention to diagnostic features that could be missed on fundus examination alone. Finally, we review what is on the horizon, including applications of artificial intelligence. Through skilled application of current and emerging imaging technologies, earlier detection of sight- and life-threatening melanocytic ocular fundus tumours can lead to improved patient prognosis.
ABSTRACT
PURPOSE: To investigate the incidence and clinical characteristics of pediatric ocular tumors in a US Midwestern county population. METHODS: Retrospective population-based cohort study of all Olmsted County, Minnesota, pediatric patients (<18 years old) diagnosed with any ocular neoplasm from January 1, 2006, to December 31, 2015. Subjects were identified via the Rochester Epidemiology Project, a record-linkage system that captures virtually all medical care provided in this county. Medical records were reviewed to confirm diagnoses. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 Olmsted County, Minnesota, pediatric population. RESULTS: There were 87 incident pediatric ocular tumor diagnoses, yielding an overall age- and sex-adjusted incidence rate of 24.0 per 100,000 per year (95% CI, 19.0-29.1). Females accounted for 46 cases (53%) cases, and 62 (85%) were White. Incidence rate for ocular tumors overall did not differ by patient age (P = 0.08) or sex (P = 0.47). All tumors were benign lesions. The most frequent adnexal/orbital, ocular surface, and intraocular tumors were epidermal inclusion cyst in 18 (21%) cases, conjunctival nevus in 10 (12%), and choroidal nevus in 18 (21%), respectively. The mean follow-up duration was 25.5 months (range, 7 days to 138.6 months), and benign tumor growth occurred in one conjunctival nevus. There were no cases of malignant transformation. CONCLUSIONS: Pediatric ocular tumors were rare with an estimated incidence of approximately 1 in 4,200 pediatric patients in Olmsted County, Minnesota. All lesions were benign, with benign growth in only 1% of cases, and no tumors underwent malignant transformation.
Subject(s)
Conjunctival Neoplasms , Nevus , Female , Humans , Child , Adolescent , Incidence , Retrospective Studies , Cohort Studies , Syndrome , Minnesota/epidemiologyABSTRACT
PURPOSE: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity "indolent T-cell lymphoproliferative disorder of the gastrointestinal tract" and illustrate the utility of fluorescence in situ hybridization for diagnosis. METHODS: This is a case report. RESULTS: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2 -rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88 , IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2 -rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. CONCLUSION: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.