Ophthalmology Commons^™

A Multicenter Study Validates The Who 2022 Classification For Conjunctival Melanocytic Intraepithelial Lesions With Clinical And Prognostic Relevance, Hardeep Singh Mudhar, Yamini Krishna, Simon Cross, Claudia Auw-Haedrich, Raymond Barnhill, Svetlana Cherepanoff, Ralph Eagle, James Farmer, Robert Folberg, Hans Grossniklaus, Martina C. Herwig-Carl, Martin Hyrcza, Sandra Lassalle, Karin U. Loeffler, Alexandre Moulin, Tatyana Milman, Robert M. Verdijk, Steffen Heegaard, Sarah E. Coupland

Wills Eye Hospital Papers

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology …

Intrinsic Disorder In Prame And Its Role In Uveal Melanoma, Michael Antonietti, David J. Taylor Gonzalez, Mak Djulbegovic, Guy W. Dayhoff, Vladimir N. Uversky, Carol L. Shields, Carol L. Karp

Wills Eye Hospital Papers

Introduction

The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME( +) Class 1 UM.

Methods

A bioinformatics study to characterize PRAME’s propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the …

Psychometric Results Of A New Patient-Reported Outcome Measure For Uveal Melanoma Post-Brachytherapy Treatment: The Prom-Um, Ezekiel Weis, Jing Jiang, Alison H. Skalet, Carol L. Shields, R. Trafford Crump

Wills Eye Hospital Papers

The objective of this study was to evaluate the psychometric properties of a new patient-reported outcome instrument intended for use with patients who have undergone brachytherapy for uveal melanoma (PROM-UM). Classical test theory and item response theory were used to evaluate the performance of individual items and domains. A convenience sample of 439 participants who had undergone brachytherapy for uveal melanoma from one of three North American ocular oncology treatment centers were included in this cross-sectional study. Exploratory factor analysis identified three domains which were labelled “Symptom Impairment”, “Worry”, and “Discomfort”. The acceptability of the instrument was supported by little …

Intratumoral Bacteria In Uveal Melanoma: A Case Report, Katherine Vega Escobar, Paola Ordonez Armijos, Tatyana Milman, Carol L. Shields, Ralph C. Eagle Jr.

Wills Eye Hospital Papers

Purpose Intratumoral bacteria and their potential application to cancer immunotherapy have been a topic of interest in recent studies. To our knowledge, bacteria in uveal melanoma have not been previously reported.

Observations We describe a patient with a large choroidal melanoma, measuring 18 × 16 mm in basal dimension and 15 mm in ultrasonographic thickness, managed by plaque brachytherapy. At the time of plaque removal, a prophylactic scleral patch graft was placed to protect from anticipated scleral necrosis. Progressive ocular ischemia led to a blind and painful eye. The enucleated eye demonstrated an extensively necrotic and heavily pigmented mushroom-shaped regressed …

Vitreoretinal Lymphoma Presenting As Frosted Branch Angiitis In A Patient With Diffuse Large B-Cell Lymphoma, Tomas Anderson, Charles G. Miller, Tian Xia, Jose S. Pulido, Alexander J. Brucker, Albert M. Maguire

Wills Eye Hospital Papers

Purpose: To describe the evaluation, diagnosis, and treatment of vitreoretinal lymphoma presenting as frosted branch angiitis in a patient with diffuse large B-cell lymphoma (DLBCL).

Observations: A 57-year-old woman with a history of non-Hodgkin lymphoma and recent DLBCL relapse presented with frosted branch angiitis that raised suspicion for an infectious retinitis but was found to be vitreoretinal lymphoma.

Conclusions and Importance: This case primarily highlights the importance of considering vitreoretinal lymphoma on the differential diagnosis of etiologies of frosted branch angiitis. Despite suspicion for vitreoretinal lymphoma, it is also important to treat empirically for infectious etiologies of retinitis in cases …

Ocular Adnexal Lymphoma: A Single-Institution Retrospective Study, César A. Fernández, Roger K. Henry, Carol L. Shields, Jurij R. Bilyk, Sara E. Lally, Ralph C. Eagle, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: To characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution. METHODS: Retrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020. RESULTS: There were 133 patients with OAL, with a median age of 65 years (range 23-97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = …

Hyperreflective Band On Anterior Segment Optical Coherence Tomography, Zaynab Sajjadi, Zeynep Bas, Carol L Shields

Wills Eye Hospital Papers

No abstract provided.

Conditional Analysis On New Tumor Formation With Solitary Unilateral Retinoblastoma In 482 Consecutive Patients, Carol L Shields, Philip W Dockery, Megan Ruben, Madalyne A Sunday, Martin Calotti, Antonio Yaghy

Wills Eye Hospital Papers

PURPOSE: The objective of the study was to understand dynamic risk (conditional analysis based on patient age) for new tumor development in patients with solitary unilateral retinoblastoma.

METHODS: This was a retrospective analysis.

RESULTS: Of 482 patients with solitary unilateral retinoblastoma, 55 new tumors developed in 20 patients (4%). Comparison (new tumor vs. no new tumor development) revealed those with new tumor demonstrated younger mean age at presentation (10 vs. 36 months,

CONCLUSION: Children (≤24 months) with solitary unilateral retinoblastoma showed decreasing risk for new tumors up to 24 months of life. Later onset of new tumor was more likely …

A Pilot Exploration Using Optical Coherence Tomography Angiography Analysis Of Capillary Vascular Density And Foveal Avascular Zone For The Diagnosis Of Uveal Melanoma, Jason Chien, Alicia Valverde-Megías, Gwo Farn Chien, Carol L Shields

Wills Eye Hospital Papers

No abstract provided.

Here Comes The Sun … For Retinoblastoma, Carol L Shields, Jerry A Shields

Wills Eye Hospital Papers

No abstract provided.

Photopsia And Visual Loss In A Patient With Lung Cancer., Eric Shiuey, Sara E. Lally, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Photodynamic Therapy In Ocular Oncology., Mehdi Mazloumi, Lauren A Dalvin, Seyed-Hossein Abtahi, Negin Yavari, Antonio Yaghy, Arman Mashayekhi, Jerry A Shields, Carol L Shields

Wills Eye Hospital Papers

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Clinical Features, Pathology, And Surgical Management Of Periocular Giant Basal Cell Carcinoma, Oxana Madalina Grosu, Vladimir Poroch, Natalia Velenciuc, Sorinel Lunca

Journal of Mind and Medical Sciences

Objectives. Basal cell carcinomas (BCCs) are malignant tumors which rarely metastasize, are slow-growing, and extensively locally destructive. BCCs more than 5 cm in diameter are defined as giant. Most often they arise as a result of neglect, as the patient avoids, delays, or refuses to see a doctor. The large tumor diameter and consequently of the post-excisional defect make these lesions difficult to treat surgically with respect to selecting the surgical reconstruction technique. Method. We studied a group of 9 patients, aged 60 to 85 years, diagnosed with giant basal cell carcinomas (GBCCs) with periocular location in which surgery was …

Ophthalmic Manifestations Of Rosai-Dorfman Disease In Five Patients, Babak Masoomian, Sara E. Lally, Jerry A Shields, Carol L Shields

Wills Eye Hospital Papers

Purpose: To report clinical features, pathology characteristics, and treatment outcomes of five patients with Rosai-Dorfman disease (RDD).

Methods: A retrospective case series of patients with RDD from the Ocular Oncology Service of Wills Eye Hospital between 1974 and 2018.

Results: There were six eyes of five patients (3 males, 2 females) with ophthalmic manifestations of RDD. The mean age at the initial presentation was 33 years (median 35, range 10-52 years). Before referral, the tumor was initially suspected to be lymphoma (n = 3), idiopathic orbital inflammation (n = 2), or pterygium (n = 1). The disease was unilateral (n …

Organ Preservation For Advanced Laryngeal Cancer: Experience With Concurrent Chemoradiation Therapy, Asif Ali Arain, Muhammad Shaheryar Ahmed Rajput, Shabbir Akhtar, Arsalan A. Rajput, Mohammad Adeel, Ahmad Hatem, Ahmed Nadeem Abbasi

Section of Otolaryngology, Head & Neck Surgery

Introduction: The larynx is a part of the upper respiratory tract that performs many essential functions including breathing, speaking, and swallowing. For this reason, the quality of life is significantly affected by laryngeal cancer and its treatment. Therefore, the focus of management for the last few decades has been on preserving the function of a larynx without compromising survival. This study was done with the purpose of reviewing our experience of organ preservation approach with concurrent chemoradiation therapy (CCRT) for locally advanced cancers of larynx.
Methods: A retrospective chart review was carried out for the data of pathology reports and …

Conjunctival Melanoma: Features Based On The Fitzpatrick Skin Type (Fst) In 540 Patients At A Single Ocular Oncology Center, Sunihidi Ramesh, Antonio Yaghy, Lauren A. Dalvin, Sara E. Lally, Jerry A. Shields, Carol L. Shields

Phase 1

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma.

Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average …

Tumors Of The Conjunctiva And Cornea., Carol L. Shields, Jerry A. Shields

Wills Eye Hospital Papers

Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary acquired melanosis, melanoma, and other ocular surface conditions like ocular melanocytosis and secondary pigmentary deposition. The most frequent nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma, both of which have typical features appreciated on clinical examination. …

Prognostication Of Uveal Melanoma Is Simple And Highly Predictive Using The Cancer Genome Atlas (Tcga) Classification: A Review., Carol L. Shields, Lauren A. Dalvin, Pornpattana Vichitvejpaisal, Mehdi Mazloumi, Arupa Ganguly, Jerry A. Shields

Wills Eye Hospital Papers

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus …

From Lepidoptera To Uveal Melanoma: Finding My Career In Ocular Oncology., Jerry A Shields

Wills Eye Hospital Papers

No abstract provided.

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Prechemotherapy And Intravenous Chemotherapy Eras., Evan B. Selzer, R. Joel Welch, Pascal Jabbour, Ann M. Leahey, Carol L. Shields

Wills Eye Hospital Papers

Purpose: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB) however, little information exists regarding its use in older patients (>5 years). In the present study, we evaluate the use of IAC (2008-2018) for RB in older patients and compare the outcomes to those in the prechemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Methods: A retrospective analysis of all patients older than 5 years treated with IAC for RB from 2008-2018. Comparisons were made to 26 active RB cases in older children treated in the prechemotherapy era and to 12 active RB cases treated in the IVC era.

Results: There were …

Changes In Ultraviolet Radiation Exposure To The Ocular Region: A Population-Based Study., Ezekiel Weis, Sebastian Q. Vrouwe, David B. Lebaron, Matthew B. Parliament, Jerry A Shields, Carol L. Shields

Wills Eye Hospital Papers

In contrast to the well-established association between ultraviolet radiation (UVR) exposure and skin cancers, the relationship between UVR and uveal malignant melanoma (UM) remains controversial. To address this controversy, we evaluated the incidence rates of cutaneous malignancies in the eyelids as a proxy for UVR exposure in the ocular region using a population-based cancer registry. Overall, 74,053 cases of eyelid basal cell carcinoma (BCC) and 7890 cases of melanoma over a 26-year period (1982–2007) were analyzed. The incidence of eyelid basal cell carcinoma and uveal melanoma remained stable, whereas other cutaneous areas demonstrated an increase in the rates. A comparability …

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Pre-Chemotherapy And Intravenous Chemotherapy Eras, Evan Selzer, Ms, R. Joel Welch, Md, Pascal Jabbour, Md, Ann Leahey, Md, Carol L. Shields, Md

Phase 1

Introduction: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB), but little information exists regarding its use in older patients (>5 years). We evaluate the use of IAC (2008-2018) for RB in older patients and compare outcomes to those in the pre-chemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Objective: To evaluate the hypothesis that IAC is effective in managing RB in older patients.

Methods: We performed a retrospective analysis of all patients older than 5 years who were treated with IAC for RB from 2008-2018 on the Ocular Oncology Service at the Wills Eye Hospital. Comparisons were made to historic, …

Bilateral Acute Ocular Ischemic Syndrome Following Head And Neck Radiation, Dipali Nemade, Paul Ferguson, Vikram Shivkumar, Dennis Cole

Marshall Journal of Medicine

Previous literature has established a clear correlation between radiation therapy (RT) to the head and neck leading to aggressive atherosclerosis of the carotid arteries and subsequent increased risk for ischemic stroke. Stenosis of carotid arteries can lead to Ocular Ischemic syndrome (OIS). We present a case of acute bilateral OIS following head and neck RT for left tonsillar squamous cell carcinoma (SCC) in a 64 year-old Caucasian male. Routine large vessel cerebrovascular screening following head and neck radiotherapy should be considered as a means of potentially mitigating future stroke risk through initiation of medical therapy and interventional modalities as a …

Comparison Of Germline Versus Somatic Bap1 Mutations For Risk Of Metastasis In Uveal Melanoma., K. G. Ewens, E. Lalonde, J. Richards-Yutz, C. L. Shields, A. Ganguly

Wills Eye Hospital Papers

BACKGROUND: Germline mutations in BAP1 have been associated with BAP1-Tumor Predisposition Syndrome (BAP1-TPDS), a predisposition to multiple tumors within a family that includes uveal melanoma (UM), cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. Alternatively, somatic mutations in BAP1 in UM have been associated with high risk for metastasis. In this study, we compare the risk of metastasis in UM that carry germline versus somatic BAP1 mutations and mutation-negative tumors.

METHODS: DNA extracted from 142 UM and matched blood samples was sequenced using Sanger or next generation sequencing to identify BAP1 gene mutations.

RESULTS: Eleven of 142 UM (8%) carried …

Long-Term Visual Outcomes In Optic Nerve Sheath Meningiomas Following Fractionated Stereotactic Radiotherapy, Sana Dastgheyb, Christian Fernandez, Md, Maria Werner-Wasik, Md, Voichita Bar-Ad, Md, David Andrews Md, James Evans, Md, Kevin Judy, Md, Sara Lally, Md, Carol Shields, Md, Arman Mashayekhi, Md, Wenyin Shi, Md, Phd, Christopher Farrell, Md

Sigma Xi Student Research Day

Introduction

Radiation therapy is often used for tumors of the optic nerve. The challenge with irradiating tumors surrounding structures associated with the eye is the risk of exposing the optic nerve, or other structures important to maintaining vision to potentially damaging radiation.

Fractionated stereotactic radiotherapy (FSRT) is commonly used for the treatment of optic nerve sheath meningiomas (ONSMs) for vision preservation. However, long term visual data in the literature is limited. We investigated visual outcomes in 27 patients with ONSMs after FSRT.

Uveal Effusion Syndrome In 104 Eyes: Response To Corticosteroids - The 2017 Axel C. Hansen Lecture., Carol L. Shields, Kelsey Roelofs, Maura Di Nicola, Kareem Sioufi, Arman Mashayekhi, Jerry A. Shields

Wills Eye Hospital Papers

PURPOSE: The purpose of the study was to investigate the corticosteroids for uveal effusion syndrome (UES).

METHODS: Retrospective series of 104 eyes with UES treated with oral corticosteroids (OCS), periocular corticosteroids (PCS), topical corticosteroids (TCS), or observation (OBS). Main outcome measure was UES resolution.

RESULTS: Of 104 eyes, treatment included OCS (n = 27), PCS (n = 12), TCS (n = 11), and OBS (n = 54). A comparison of the four groups (OCS vs. PCS vs. TCS vs. OBS) revealed differences in those managed with OCS versus OBS as younger (66 vs. 72 years, P = 0.049), PCS versus …

Phosphorylation Of Prb: Mechanism For Rb Pathway Inactivation In Mycn-Amplified Retinoblastoma., Kathryn G. Ewens, Tricia R. Bhatti, Kimberly A. Moran, Jennifer Richards-Yutz, Carol L. Shields, Ralph C. Eagle Jr., Arupa Ganguly

Wills Eye Hospital Papers

A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) …

Advancing Vibrational Spectroscopy For Cellular And Sub Cellular Analysis: Raman Spectroscopy As An In Vitro Chemotherapeutic Screeening And Assessment Protocol, Zeineb Farhane

Doctoral

Vibrational spectroscopy, including Raman micro-spectroscopy, has attracted considerable attention over the last few years, as a powerful, non-invasive tool for clinical applications, especially in cancer diagnosis, in vivo and ex vivo. As a molecular fingerprinting technique with optical resolution, Raman micro-spectroscopy is able to monitor biochemical processes, drug uptake, efficacy and mode of action and mechanisms of interaction of chemotherapeutic drugs at a subcellular level. In vitro applications may be more strategically achievable, and can help guide drug design and discovery, and eventually evaluate To this end, different lung cell lines were used and Raman micro-spectroscopy was coupled to valuable …

Choroidal Metastasis From Leiomyosarcoma In Two Cases, Eric Feinstein, Swathi Kaliki, Carol L Shields, Hormoz Ehya, Jerry A Shields

Wills Eye Hospital Papers

Leiomyosarcoma is a malignant tumor of mesenchymal cells and is the most common soft-tissue sarcoma. Leiomyosarcoma is a notably rare tumor in the ophthalmic region and can be of primary, secondary or metastatic origin. To the best of our knowledge, there has only been one published case of leiomyosarcoma metastasis to the choroid. In this case study, we report two cases of primary leiomyosarcoma with metastasis to the choroid of the eye. Both cases displayed systemic metastasis and showed response to high dose plaque radiotherapy. Despite its prevalence as the leading form of sarcoma, leiomyosarcoma rarely metastasizes to the ocular …

Breast Cancer Medications And Vision: Effects Of Treatments For Early-Stage Disease, Alvin Eisner, Shiuh-Wen Luoh

Community Health Faculty Publications and Presentations

This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve …