Publications by authors named "Jerry A Shields"

618 Publications

Ten-year outcomes of uveal melanoma based on The Cancer Genome Atlas (TCGA) classification in 1001 cases.

Indian J Ophthalmol 2021 Jul;69(7):1839-1845

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To understand the prognostic value of The Cancer Genome Atlas (TCGA) for uveal melanoma metastasis, using a simplified 4-category classification, based on tumor DNA.

Methods: A retrospective cohort study of 1001 eyes with uveal melanoma at a single center, categorized according to TCGA as Group A, B, C, or D (by fine-needle aspiration biopsy for DNA analysis), and treated with standard methods, was studied for melanoma-related metastasis at 5 and 10 years.

Results: Of 1001 eyes with uveal melanoma, the TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). By comparison, increasing category (A vs. B vs. C vs. D) was associated with features of older age at presentation (56.8 vs. 52.8 vs. 61.1 vs. 63.5 years, P < 0.001), less often visual acuity of 20/20-20/50 (80% vs. 67% vs. 70% vs. 65%, P = 0.001), tumor location further from the optic disc (P < 0.001) and foveola (P < 0.001), and greater median tumor basal diameter (10.0 vs. 13.0 vs. 14.0 vs. 16.0 mm, P < 0.001) and tumor thickness (3.5 vs. 5.2 vs. 6.0 vs. 7.1 mm, P < 0.001). The Kaplan-Meier (5-year/10-year) rate of metastasis was 4%/6% for Group A, 12%/20% for Group B, 33%/49% for Group C, and 60%/not available for Group D.

Conclusion: A simplified 4-category classification of uveal melanoma using TCGA, based on tumor DNA, is highly predictive of risk for metastatic disease.
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http://dx.doi.org/10.4103/ijo.IJO_313_21DOI Listing
July 2021

Swiss Cheese-Appearing Cavitary Ciliochoroidal Melanoma.

Ophthalmol Retina 2021 Jun;5(6):592

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 840 Walnut Street, 14th Floor, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.oret.2021.02.016DOI Listing
June 2021

Retinocytoma/retinoma: comparative analysis of clinical features in 78 tumors and rate of transformation into retinoblastoma over 20 years.

J AAPOS 2021 May 26. Epub 2021 May 26.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To explore clinical features and long-term outcomes in patients with retinocytoma/retinoma.

Methods: The medical records of patients with retinocytoma/retinoma over a 20-year period were reviewed retrospectively to compare patient age at presentation (<4 vs ≥4 years), tumor type, and tumor focality (unifocal vs multifocal).

Results: Of 2,021 patients with retinoblastoma, 62 (3%; median age, 5 years; 85% white; 58% male) had 78 tumors: 54 retinocytoma (69%) and 24 retinoma (31%). Median basal tumor diameter was 6.0 mm; mean thickness, 2.3 mm. Younger patients (<4 years) were more likely Hispanic (19% vs 2%; P = 0.04), with leukocoria (24% vs 0%; P = 0.003), and with calcification in ≤50% of the tumor (96% vs 70%; P = 0.007). Compared with retinoma, retinocytoma was more prevalent in older patients (median age, 9 vs 2 years; P < 0.001), with fewer symptoms (38% vs 69%; P = 0.04), larger median basal diameter (7.0 vs 3.0 mm; P < 0.001), greater thickness (2.5 vs 1.6 mm; P = 0.02), and less frequently with additional retinoblastoma in either eye (9% vs 71%; P < 0.0001). Compared with multifocal tumors, unifocal tumors occurred more frequently with lack of symptoms (62% vs 25%; P = 0.03), greater median basal diameter (6.0 vs 3.3; P = 0.003), and greater thickness (2.5 vs 1.5 mm; P = 0.006). Tumor transformation into retinoblastoma was found in 2.7% by 2 years, 9.2% by 5 years, 15.3% by 10-20 years. The only factor predictive of transformation was increasing thickness (P = 0.003; hazard ratio of 2.83 per 1 mm increase).

Conclusions: In our study cohort, the rate of retinocytoma/retinoma transformation into retinoblastoma increased from 2 to 10-20 years of age. The only factor predictive of transformation was increasing tumor thickness.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.024DOI Listing
May 2021

Intra-arterial chemotherapy for retinoblastoma in 341 consecutive eyes (1,292 infusions): comparative analysis of outcomes based on patient age, race, and sex.

J AAPOS 2021 May 24. Epub 2021 May 24.

Department of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate tumor control and globe salvage following intra-arterial chemotherapy (IAC) for retinoblastoma based on International Classification of Retinoblastoma (ICRB) and patient demographics.

Methods: The medical records of 313 patients (341 eyes) treated with IAC were reviewed retrospectively. Chemotherapy agents included melphalan, topotecan, and carboplatin. Comparative analysis was performed for tumor control and globe salvage based on ICRB and patient demographics including age (≤12 vs >12 months), race (white vs nonwhite), and sex.

Results: Of the 341 eyes treated with 1,292 consecutive infusions of IAC as primary or secondary therapy for retinoblastoma, Kaplan-Meier 5-year estimates of globe salvage was 74%. Of those treated with IAC as primary therapy (n = 160 eyes; 655 infusions), 5-year globe salvage overall was 76%: and more specifically, 100% for groups B and C, 86% for group D, and 55% for group E. Of those treated with IAC as secondary therapy (n = 207 eyes; 859 infusions), 5-year globe salvage was 71%. Comparative analysis by race and sex demonstrated no differences in outcomes, but analysis by age revealed that younger patients had a higher rate of globe salvage (77% vs 72%; P < 0.001). Complications (per catheterization) included retina ischemia (1%), choroidal ischemia (1%), neovascularization of the disk, retina, iris (NVI), glaucoma (about 1% each), and central/peripheral systemic ischemia (<1%). Younger patients showed less NVI (P = 0.028), white patients showed less retinal ischemia (P = 0.037), and no difference by sex. There were no patients with metastatic disease or death.

Conclusions: Our results suggest that IAC provides substantial tumor control for advanced and/or recurrent retinoblastoma with a high rate of globe salvage and few complications. There was little difference in outcomes per age, race, and sex.
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http://dx.doi.org/10.1016/j.jaapos.2020.12.006DOI Listing
May 2021

Photodynamic Therapy (PDT) for Retinal Hemangioblastoma: Treatment Outcomes in 17 Consecutive Patients.

Ophthalmol Retina 2021 Apr 20. Epub 2021 Apr 20.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA. Electronic address:

Purpose: To report the efficacy of photodynamic therapy (PDT) for management of retinal hemangioblastoma.

Design: Retrospective case series.

Participants: Seventeen patients with retinal hemangioblastoma treated with PDT.

Methods: The medical records of 17 patients with retinal hemangioblastoma treated with PDT were reviewed and treatment outcomes were assessed. Photodynamic therapy was performed with verteporfin infusion intravenously at a dose of 6 mg/m body surface area over 10 minutes, followed by application of 50 J/cm laser light at 689 nm for 83 or 166 seconds.

Main Outcome Measures: Tumor control, subretinal/intraretinal fluid resolution, visual outcome.

Results: There were 18 retinal hemangioblastomas in 17 eyes treated with PDT. Median patient age was 31 years (mean 36 years, range 7-66 years), and median follow up was 51 months (mean 61 months, range 2-144 months). Genetic testing confirmed von Hippel-Lindau disease in 8/17 (47%) patients, and ocular symptoms were present in 12/17 (71%) patients. The tumors were unilateral in all patients and unifocal in the majority of patients (n=13/17, 76%). The tumor median basal diameter was 3.5 mm (mean 3.4 mm, range 1.5-6.0 mm) and median thickness was 2.1 mm (mean 2.3 mm, range 1.0-5.0 mm). The tumor location was juxtapapillary in 9/18 cases (50%). Associated findings included exudation (n=14/17, 82%), subretinal fluid (n=14/17, 82%), and macular edema (n=12/17, 71 %). The median number of PDT sessions was 1.5 (mean 1.8, range 1.0-4.0). Standard duration PDT (83 seconds) was used in all cases except 2, in which double duration (166 seconds) was used. Post-PDT transient exudative response occurred in 4/17 (24%) eyes. Outcomes revealed tumor control in 13/18 (72%) tumors, partial or complete resolution of subretinal fluid in 10/14 (71%) and macular edema in 7/12 (58%) eyes, and visual acuity stable or improved in 12/17 (71%) eyes. Photodynamic therapy-related transient exudative response was noted in 4/17 (24%) eyes.

Conclusion: Photodynamic therapy is an effective treatment for both juxtapapillary and peripheral retinal hemangioblastomas, providing satisfactory rates of tumor control and visual stabilization/improvement. Patients should be monitored for PDT-related transient exudative response.
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http://dx.doi.org/10.1016/j.oret.2021.04.007DOI Listing
April 2021

Conjunctival melanoma: outcomes based on tumour origin in 629 patients at a single ocular oncology centre.

Eye (Lond) 2021 Mar 26. Epub 2021 Mar 26.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To investigate clinical features and outcomes of conjunctival melanoma classified by tumour origin.

Methods: Retrospective review of conjunctival melanoma patients at a single ocular oncology centre between April 18, 1974 and September 9, 2019. Lesions were divided into three tumour origin groups (primary acquired melanosis [PAM], nevus, and de novo) and clinical features and outcomes were compared.

Results: There were 629 patients with conjunctival melanoma that arose from PAM (n = 476, 76%), nevus (n = 59, 9%), or de novo (n = 94, 15%). A comparison (PAM vs. nevus vs. de novo) revealed patients with tumours arising from PAM presented with older mean age (62 vs. 52 vs. 55 years, p < 0.001), worse initial logMAR visual acuity (Snellen equivalent 20/30 vs. 20/25 vs. 20/25, p = 0.03), and greater clock hour involvement (4.8 vs. 4.0 vs. 3.2, p < 0.001). Tumours arising from nevus had lower frequency of fornix (31% vs. 9% vs. 24%, p = 0.02) and tarsal involvement (29% vs. 9% vs. 26%, p = 0.046) and more frequent classification as AJCC category T1 (60% vs. 89% vs. 62%, p = 0.01). After follow-up of (57.2 vs. 68.2 vs. 51.7 months, p = 0.35), tumours arising from PAM had worse mean final visual acuity (20/50 vs. 20/40 vs. 20/40, p = 0.02) and greater frequency of visual acuity loss ≥3 lines (25% vs. 15% vs. 10%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by tumour origin for visual acuity loss ≥3 lines, local tumour recurrence, exenteration, metastasis, or death.

Conclusions: Conjunctival melanoma most often arose from PAM, and tumour origin did not affect clinical outcomes.
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http://dx.doi.org/10.1038/s41433-021-01508-yDOI Listing
March 2021

Primary treatment of ocular surface squamous neoplasia with topical interferon alpha-2b: Comparative analysis of outcomes based on original tumor configuration.

Indian J Ophthalmol 2021 03;69(3):563-567

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: The aim of this study was to evaluate tumor control of OSSN with topical IFNα2b alone based on tumor configuration (flat versus (vs.) dome-shaped).

Methods: Retrospective, nonrandomized, interventional cohort study on 64 consecutive tumors in 63 patients with OSSN treated with topical IFNα2b. Topical IFNα2b (1 million international units/cc) was compounded and provided by the Thomas Jefferson University Hospital Pharmacy to be refrigerated and applied 4 times daily until biomicroscopic evidence of tumor resolution was observed.

Results: The tumor configuration was flat (n = 15, 23%) or dome-shaped (n = 49, 77%). A comparison (flat vs. dome-shaped) revealed dome-shaped with older mean patient age at presentation (62 vs. 70 years, P = 0.04), greater patient history of smoking (13% vs. 42%, P = 0.04), greater corneal involvement (7% vs. 82%, P < 0.001), larger mean basal diameter (5.5 vs. 12.4 mm, P = 0.001) and mean thickness (1.9 vs. 4.3, P = 0.002), and longer mean duration IFNα2b therapy (3.7 vs. 6.3 months, P = 0.002). There was no difference in mean follow-up time (22.2 vs 23.1 months) or time to complete response (5.0 vs. 6.1 months). There was no difference in achievement of complete tumor control with IFNα2b alone (93% vs. 96%). There were no cases with metastasis or death.

Conclusion: Topical IFNα2b alone shows excellent overall tumor control of 95% with no difference in efficacy based on tumor configuration.
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http://dx.doi.org/10.4103/ijo.IJO_1665_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942118PMC
March 2021

Overlapping Immunohistochemical Features of Adenocarcinoma of the Nonpigmented Ciliary Body Epithelium and Renal Cell Carcinoma.

Am J Ophthalmol 2021 Jan 30;226:191-200. Epub 2021 Jan 30.

From the David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.

Purpose: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma.

Design: Retrospective case series.

Methods: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor.

Results: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors.

Conclusions: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis.
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http://dx.doi.org/10.1016/j.ajo.2021.01.020DOI Listing
January 2021

Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

Ophthalmol Retina 2021 Jan 7. Epub 2021 Jan 7.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Purpose: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures.

Design: Retrospective study.

Participants: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included.

Methods: Clinical records were reviewed retrospectively.

Main Outcome Measures: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death.

Results: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1).

Conclusions: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.
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http://dx.doi.org/10.1016/j.oret.2020.12.025DOI Listing
January 2021

Boom-Boom Radiotherapy for Choroidal Lymphoma-Two Days and Done.

Ophthalmol Retina 2021 01;5(1):15

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.oret.2020.09.002DOI Listing
January 2021

Conjunctival Melanoma: Outcomes based on the American Joint Committee on Cancer Clinical Classification (8th Edition) of 425 Patients at a Single Ocular Oncology Center.

Asia Pac J Ophthalmol (Phila) 2020 Dec 9;10(2):146-151. Epub 2020 Dec 9.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.

Purpose: The aim of this study was to evaluate outcomes of conjunctiva melanoma based on the American Joint Committee on Cancer Classification (AJCC) 8th edition.

Design: Retrospective interventional case series.

Methods: Outcomes analysis of 425 patients.

Results: In this analysis of 425 patients with conjunctival melanoma, there were 266 (63%) patients classified as T1, 75 (18%) as T2, 84 (20%) as T3, and 0 (0%) as T4. A comparison (T1 vs T2 vs T3) revealed that history of primary acquired melanosis was more common in T2 (81% vs 96% vs 81%; P = 0.01) and conjunctival nevus more common in T1 (20% vs 9% vs 11%; P = 0.03). Of 381 patients with follow-up (mean of 57.6 months), comparison revealed higher T category with increasing local recurrence/new tumor (30% vs 43% vs 49%; P = 0.004), increasing exenteration (3% vs 9% vs 28%; P < 0.001), increasing melanoma-related locoregional lymph node metastasis (2% vs 7% vs 12%; P = 0.001), increasing melanoma-related systemic metastasis (9% vs 25% vs 23%; P < 0.001), and increasing melanoma-related death (4% vs 12% vs 18%; P < 0.001). A comparison at 10 years revealed visual acuity loss of >3 lines (32% vs 42% vs 63%; P < 0.001), melanoma recurrence/new tumor (47% vs 70% vs 74%; P < 0.001), exenteration (4% vs 24% vs 46%; P < 0.001), melanoma-related locoregional lymph node metastasis (3% vs 13% vs 25%; P < 0.001), melanoma-related systemic metastasis (13% vs 45% vs 40%; P < 0.001), and melanoma-related death (8% vs 22% vs 37%; P < 0.001).

Conclusions: Based on the AJCC 8th edition of conjunctival melanoma, the 10-year risk per T category significantly increased for visual acuity loss of >3 lines, recurrence/new tumor, exenteration, locoregional and systemic melanoma-related metastasis, and melanoma-related death.
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http://dx.doi.org/10.1097/APO.0000000000000343DOI Listing
December 2020

Ocular Surface Squamous Neoplasia Managed With Primary Interferon α2b: A Comparative Analysis of 212 Tumors in Smokers Versus Nonsmokers.

Cornea 2020 Dec 3. Epub 2020 Dec 3.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA.

Purpose: To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status.

Methods: Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b.

Results: There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes.

Conclusions: Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence.
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http://dx.doi.org/10.1097/ICO.0000000000002615DOI Listing
December 2020

Conjunctival melanoma: Risk factors for recurrent or new tumor in 540 patients at a single ocular oncology center.

Eur J Ophthalmol 2020 Nov 11:1120672120970393. Epub 2020 Nov 11.

Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To investigate risk factors for recurrent or new tumor in patients with conjunctival melanoma.

Methods: Retrospective review of patients with conjunctival melanoma managed on the Ocular Oncology Service, Wills Eye Hospital from 1974 to 2019.

Results: There were 540 patients with mean follow-up of 57.6 months, of whom 176 (33%) had recurrent or new tumor formation. Risk factors for recurrent or new tumor on univariate analysis included presentation at older age (OR: 1.02 [1.01-1.03] per 1-year increase in age,  = 0.002), history of prior conjunctival surgery (OR: 1.62 [1.05-2.49],  = 0.03), worse visual acuity at presentation (OR: 1.76 [1.04-2.98] per 1 log-unit increase,  = 0.04), more advanced AJCC clinical T-subcategory (OR: 1.08 [1.02-1.14] per 1 subcategory increase,  = 0.01), tumor primary location in tarsal conjunctiva (OR: 1.80 [1.09-2.98],  = 0.02), and secondary tumor involvement of the fornix (OR: 1.68 [1.06-2.65],  = 0.03), and eyelid (OR: 1.92 [1.07-3.43],  = 0.03). Risk factors on multivariate analysis using all demographics, clinical features, and tumor location included presentation at older age (OR: 1.02 [1.00-1.03],  = 0.01), history of prior conjunctival surgery (OR: 1.84 [1.16-2.94],  = 0.01), and more advanced AJCC clinical T-subcategory (OR: 1.07 [1.01-1.13] per one subcategory increase,  = 0.03).

Conclusion: On multivariate analysis, the strongest predictors of recurrent or new tumor formation following treatment of conjunctival melanoma included older age, history of prior conjunctival surgery, and advanced AJCC T-subcategory. These results suggest that earlier detection and the first surgery in conjunctival melanoma management are critical for prevention of recurrent or new tumor, and we recommend prompt referral to an experienced surgeon.
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http://dx.doi.org/10.1177/1120672120970393DOI Listing
November 2020

Photodynamic Therapy in Ocular Oncology.

J Ophthalmic Vis Res 2020 Oct-Dec;15(4):547-558. Epub 2020 Oct 25.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, USA.

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.
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http://dx.doi.org/10.18502/jovr.v15i4.7793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591845PMC
October 2020

Muir-Torre Syndrome Associated Periocular Sebaceous Neoplasms: Screening Patterns in the Literature and in Clinical Practice.

Ocul Oncol Pathol 2020 Aug 15;6(4):226-237. Epub 2020 Jan 15.

Department of Ophthalmic Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines.

Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37-79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear.

Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.
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http://dx.doi.org/10.1159/000504984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506251PMC
August 2020

Usefulness of PAX8 Immunohistochemistry in Adult Intraocular Tumor Diagnosis.

Ophthalmology 2021 May 29;128(5):765-778. Epub 2020 Sep 29.

Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of intraocular tumors.

Design: Observational case series.

Participants: Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas.

Methods: Hematoxylin-eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed.

Main Outcome Measures: Distribution of PAX8 expression in normal and neoplastic tissue.

Results: Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic tumors (iris melanoma, ciliary-choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma.

Conclusions: PAX8 has proven to be a very useful diagnostic marker in a select group of adult intraocular tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging intraocular neoplasms.
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http://dx.doi.org/10.1016/j.ophtha.2020.09.033DOI Listing
May 2021

Immunohistochemical Profiling of Conjunctival Melanocytic Intraepithelial Lesions, Including SOX10, HMB45, Ki67, and P16.

Am J Ophthalmol 2021 02 28;222:148-156. Epub 2020 Sep 28.

Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Pathology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

Purpose: To determine the usefulness of melan-A, SOX10, HMB45, and p16 immunohistochemical stains in the distinction between the low-grade and high-grade conjunctival melanocytic intraepithelial lesions, either independently or as components of an immunohistochemical panel.

Design: Retrospective observational case series.

Methods: Institutional pathology records between 2014 and 2018 were searched for all patients with conjunctival melanocytic intraepithelial lesions. Biopsies without supporting clinical history or tissue available for review and immunohistochemical analysis were excluded. Clinical, histopathologic, and immunohistochemical (p16, SOX10, HMB45, and Ki-67) findings were recorded.

Results: Thirty-one patients underwent 47 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were low-grade conjunctival melanocytic intraepithelial lesion (n = 18, 38%) and high-grade conjunctival melanocytic intraepithelial lesion/melanoma in situ (n = 29, 62%). The addition of melan-A and SOX10 immunohistochemical stains resulted in an upgrade of conjunctival melanocytic intraepithelial lesion from low-grade to high-grade in 2 (4%) of 47 cases. The addition of melan-A and SOX10 immunohistochemical stains did not downgrade any of the histomorphologically high-grade lesions. In a clinical-pathologic multivariable model, the parameters most predictive of high-grade melanocytic intraepithelial lesion/melanoma in situ were involvement of the caruncle (odds ratio [OR] = 19, confidence interval [CI] 1.6-212; P = .02] and p16 cytoplasmic H-score >30 (OR = 81, CI 2.7 to >999; P = .01) CONCLUSION: Although the stains for melanocytic markers melan-A and SOX10 facilitate assessment of melanocytic intraepithelial lesions, the current immunohistochemical panels have limited value in distinction between the low-grade and high-grade intraepithelial melanocytic proliferations and need to be used judiciously.
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http://dx.doi.org/10.1016/j.ajo.2020.09.033DOI Listing
February 2021

Multimodal imaging of chorioretinal folds induced by orbital vascular malformation in two cases.

Eur J Ophthalmol 2020 Sep 19:1120672120957582. Epub 2020 Sep 19.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA USA.

Purpose: To investigate the alterations in the retinal pigment epithelium (RPE) in the crest and trough portions of chorioretinal folds (CRFs) induced by an orbital vascular tumor.

Methods: Review of multimodal imaging in two eyes of two patients with globe compression and CRFs from an orbital vascular tumor.

Results: Fundus photography demonstrated obliquely extending CRFs with alternating hyperpigmented and hypopigmented linear alterations in both eyes. Fundus autofluorescence (AF) imaging showed obliquely oriented hypoAF lines, incompletely alternating with hyperAF lines. In Case 1, the hyperAF lines had interspersed hypoAF segments and Case 2 had peripapillary mottling of AF. Fluorescein angiography (FA) showed alternating hyper and hypofluorescent lines in the late phase in Case 1. Optical coherence tomography (OCT) documented relative thinning of RPE at the folded crests in Case 1 and preservation of RPE in Case 2. Swept-source OCT angiography (SS-OCTA) demonstrated oblique hyporeflective lines in the outer retina and choriocapillaris layers in Case 2. These findings suggest that the crest of a CRF represents thinned or rarified RPE with hypoAF, transmission hyperfluorescence (FA), partially attenuated RPE layer (OCT), and isoreflectivity (SS-OCTA) while the trough represents compressed RPE with irregular hyperAF, transmission hypofluorescence (FA), thickened RPE layer (OCT), and hyporeflectivity (SS-OCTA).

Conclusion: The anatomic and functional status of the RPE in CRFs based on multimodal imaging reveals normal to attenuated RPE with hypofunctionality at the fold crest and compacted, thickened RPE at the trough with segmental functional impairment on AF imaging. Anatomic information regarding CRFs is evident on OCT, FA, and SS-OCTA while the functional status is depicted on AF.
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http://dx.doi.org/10.1177/1120672120957582DOI Listing
September 2020

Lacrimal drainage apparatus melanoma remotely following treatment and resolution of conjunctival melanoma.

Orbit 2020 Aug 18:1-8. Epub 2020 Aug 18.

Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Lacrimal drainage apparatus melanoma is a rare entity that may arise primarily or, more commonly, as secondary involvement from melanoma originating elsewhere. Conjunctival melanoma may involve the lacrimal drainage apparatus (LDA) via spread along the canalicular epithelium, separate in situ processes, or direct invasion. Only seven cases exist in the literature where conjunctival melanoma remotely recurred in the LDA. We report three additional patients, two with invasive conjunctival melanoma and one with primary acquired melanosis (PAM) with severe atypia/melanoma in situ, who developed LDA melanoma at 5, 8, and 16 years after initial treatment of conjunctival melanoma. This report confirms the ability of conjunctival melanoma to give rise to spatially and temporally remote LDA melanoma despite adequate local treatment, and reviews the proposed mechanisms and associated characteristics of LDA recurrence in conjunctival melanoma.
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http://dx.doi.org/10.1080/01676830.2020.1808020DOI Listing
August 2020

Ophthalmic Manifestations of Rosai-Dorfman Disease in Five Patients.

J Curr Ophthalmol 2020 Jul-Sep;32(3):238-243. Epub 2020 Jul 4.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

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 ( = 3), idiopathic orbital inflammation ( = 2), or pterygium ( = 1). The disease was unilateral ( = 4) or bilateral ( = 1). The mean duration of symptoms was 9 months (median 8, range 5-24 months). The disease produced nodules in the conjunctiva ( = 4) or orbit ( = 2). Two patients with conjunctival involvement had corneal involvement. One patient with bilateral conjunctiva lesions demonstrated bilateral orbital involvement and bilateral anterior uveitis. The mean tumor basal dimension was 13 mm (median 9, range 6-27 mm) for conjunctiva lesions and 37 mm (median 37, range 34-40 mm) for orbital lesions. The main symptom (per patient) included proptosis ( = 2), palpable mass ( = 1), and foreign body sensation ( = 2). No patient experienced pain or tenderness. Palpable, nontender lymphadenopathy was detectable in two patients in the cervical and inguinal lymph nodes. Systemic involvement with paranasal sinusitis and mediastinal/pulmonary lymphadenopathy occurred in two patients, both with orbital involvement. Surgical resection was performed for all patients. At a mean follow-up of 31 months (median 12, range, 10-76 months) after the surgery, tumor control was achieved in all six eyes without local recurrence.

Conclusion: In this series of six eyes with RDD, patients with orbital and/or intraocular disease were more likely to demonstrate lymphadenopathy and systemic involvement, while those with unilateral perilimbal conjunctival tumors remained localized.
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http://dx.doi.org/10.4103/JOCO.JOCO_84_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382521PMC
July 2020

Conjunctival Melanoma: Outcomes Based on Age at Presentation in 629 Patients at a Single Ocular Oncology Center.

Cornea 2021 May;40(5):554-563

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA. Dr. Dalvin has an appointment with the Department of Ophthalmology, Mayo Clinic, Rochester, MN.

Purpose: To investigate the clinical features and outcomes for conjunctival melanoma based on patient age.

Methods: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Clinical features and outcomes were compared by patient age category at presentation (young ≤45 years, middle-aged 46-69 years, and older ≥70 years), with Kaplan-Meier and Cox proportional hazard analysis [hazard ratio (95% confidence interval)].

Results: There were 629 patients categorized as young in 130 (21%), middle-aged in 278 (44%), and older in 221 (35%). A comparison by age category (young vs. middle-aged vs. older) revealed that older patients had melanoma with greater number of affected quadrants (1.7 vs. 1.8 vs. 2.0, P = 0.001) and clock hours (3.9 vs. 4.2 vs. 5.2, P = 0.001). All patients were treated with surgical excision, with no difference in requirement for additional medical or radiation therapy. By 10-year Kaplan-Meier outcomes, older patients had more frequent visual acuity loss ≥3 lines (11% vs. 28% vs. 64%, P < 0.001) and local tumor recurrence (38% vs. 46% vs. 70%, P < 0.001). Hazard ratio for the oldest age group (age ≥70) revealed a 7.76-fold (3.33-18.09) increased risk for visual acuity loss (P < 0.001), and a 2.08-fold (1.32-3.28) increased risk of local tumor recurrence (P = 0.002). There was no difference by age in risk for enucleation, exenteration, locoregional lymph node involvement, distant systemic metastasis, or death.

Conclusions: Older patients with conjunctival melanoma present with more extensive disease and have increased risk for visual acuity loss and local tumor recurrence.
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http://dx.doi.org/10.1097/ICO.0000000000002449DOI Listing
May 2021

Eye cancer in a young male with a vaping history.

Indian J Ophthalmol 2020 Aug;68(8):1699-1701

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

We report a new observation of conjunctival intraepithelial neoplasia (CIN) in a young man following years of electronic cigarette use. A 22-year-old man with a 5-year electronic cigarette use (vaping) developed painless unilateral blurred vision in the right eye from mild superficial corneal opacification, unresponsive to topical antiviral therapy. Corneal scraping documented no infectious etiology. The abnormality persisted for 1 year and superficial keratectomy revealed high-grade CIN with enlarged pleomorphic and dyskeratotic cells. Interferon-alpha-2b was instituted. In this case, chronic exposure to electronic cigarette vapors (vaping) could have been associated with CIN in this young patient.
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http://dx.doi.org/10.4103/ijo.IJO_27_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640851PMC
August 2020

Conjunctival nevi and melanoma: multiparametric immunohistochemical analysis, including p16, SOX10, HMB45, and Ki-67.

Hum Pathol 2020 09 21;103:107-119. Epub 2020 Jul 21.

Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, 19107, USA; Department of Pathology, Wills Eye Hospital, Philadelphia, PA, 19107, USA.

The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4-457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2-77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.
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http://dx.doi.org/10.1016/j.humpath.2020.07.020DOI Listing
September 2020

Unique Geospatial Accumulations of Uveal Melanoma.

Am J Ophthalmol 2020 12 16;220:102-109. Epub 2020 Jul 16.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Purpose: The main purpose of this paper was to describe the unique accumulation of cases of uveal melanoma (UM). All patients were white and did not have known occupational risk factors. From the authors' standpoint, there were no lifestyle factors in common in the reported cases. Results of more extensive analyses, including geospatial analysis, are currently being conducted and will be presented in a separate paper.

Design: Observational case series.

Methods: Descriptive data from medical records, patient interviews, and questionnaires were obtained from 5 patients from North Carolina, 6 patients from Alabama, and 14 patients from New York. Standard incidence ratio (SIR) calculations were provided by the respective states' cancer registries. UM is the most common primary malignant eye tumor in adults, although it is rare, with 2,500 cases diagnosed annually in the United States. Despite a growing understanding of the molecular characteristics, there remains uncertainty regarding epidemiologic trends and environmental risk factors. This study identified 3 geographic accumulations of UM: 1) Huntersville, NC; 2) Auburn, AL; and 3) Broome and Tioga Counties, New York. Investigation of these groups will guide ongoing efforts to discover potential risk factor and assist with future treatment and prevention.

Results: In North Carolina, 5 females who were identified as living in Huntersville, NC, were diagnosed with UM at ages 20, 22, 24, 30, and 31. The SIR calculations considering the observed and expected incidence ratios was 0.7 (95% confidence interval [CI], 0.5-0.9) in Mecklenburg County. In Alabama, 6 individuals who were identified as either attending Auburn University or employed there from 1989 to 1993 had diagnoses of UM. Initial SIR calculations for white females of all ages was 1.15 (95% CI, 0.989-1.328). In New York, SIR for Broome and Tioga counties were 0.93 and not significant. However, in Tioga county, for males and females and females alone, SIRs were 2.00 (P = .04) and 3.33 (P = .006).

Conclusions: Although most of the conclusions that the SIR does not meet statistical criteria that defines these accumulations as true "cancer clusters," considering the incidence and demographics of UM, these accumulations of cases is unexpected and worth additional exploration. Further investigation into these cases with additional geospatial analyses and blood and tumor testing is ongoing. Information learned from the study of these unique populations may inform a better understanding of the pathogenesis of UM.
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http://dx.doi.org/10.1016/j.ajo.2020.07.012DOI Listing
December 2020

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

Ophthalmology 2020 11 22;127(11):1567-1577. Epub 2020 Apr 22.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course.

Design: Multicenter retrospective observational case series.

Participants: Sixty-three patients with SIC in 1 eye.

Methods: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography.

Main Outcome Measures: Standardized grading of imaging features.

Results: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution.

Conclusions: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.018DOI Listing
November 2020

ASSOCIATION OF VITREORETINAL LYMPHOMA WITH SYSTEMIC LYMPHOMA.

Retina 2021 Feb;41(2):259-265

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Dr. Dalvin is now with the Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.

Purpose: To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL).

Methods: Single-center retrospective review of medical records.

Results: Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate.

Conclusion: We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.
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http://dx.doi.org/10.1097/IAE.0000000000002855DOI Listing
February 2021

Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium: A Review of 51 Consecutive Patients.

Ophthalmol Retina 2020 08 18;4(8):829-839. Epub 2020 Mar 18.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Purpose: To describe the clinical and imaging characteristics, pathologic features, and management options of retinal pigment epithelium (RPE) adenoma/adenocarcinoma.

Design: Retrospective case series.

Participants: Fifty-one patients with RPE adenoma/adenocarcinoma.

Methods: Treatment options for the patients included observation, partial lamellar sclerouvectomy (PLSU), enucleation, and others.

Main Outcome Measures: Factors related to visual acuity (VA) outcomes (>2 Snellen lines loss, poor final VA [≤20/200], good final vision [≥20/40]), tumor growth, and need for enucleation.

Results: The mean patient age at diagnosis was 51 years, and the majority of patients were white (40/51, 78%) and female (34/51, 67%). Primary management included observation (29/51, 57%), PLSU (9/51, 18%), enucleation (4/51, 8%), or others (9/51, 18%). Outcomes revealed decreased VA (10/32, 31%), poor final VA (17/32, 53%), good final VA (11/32, 34%), tumor growth (12/25, 48%), and need for enucleation (7/51, 14%). By multivariable analysis, features predictive of decreased VA included increasing baseline tumor thickness (P = 0.01) and presence of vitreous hemorrhage (P = 0.05). Factors predictive of poor final VA included presence of exudative retinal detachment (P = 0.004), baseline VA 20/50 to 20/150 (P = 0.008), and baseline VA ≤20/200 (P = 0.01). Absence of feeding and/or draining vessel was predictive of good VA (P = 0.004). Tumor growth was associated with multiple treatments (P = 0.02). Increased tumor thickness (P = 0.03) and presence of exudative retinal detachment (P = 0.01) were predictive of enucleation.

Conclusion: RPE adenoma/adenocarcinoma can simulate choroidal melanoma. Greater tumor thickness, vitreous hemorrhage, exudative retinal detachment, and poor baseline VA predict worse visual outcome and greater risk for enucleation.
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http://dx.doi.org/10.1016/j.oret.2020.03.008DOI Listing
August 2020

Lacrimal Gland Hamartoma (Formerly Termed Dacryoadenoma).

Am J Ophthalmol 2020 09 29;217:189-197. Epub 2020 Apr 29.

Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: Since the original description of "dacryadenoma" by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion.

Design: Retrospective observational case series.

Methods: Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded.

Results: Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%).

Conclusion: Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.
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http://dx.doi.org/10.1016/j.ajo.2020.04.015DOI Listing
September 2020

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

Retina 2021 Feb;41(2):249-258

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL).

Methods: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019.

Results: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression.

Conclusion: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.
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http://dx.doi.org/10.1097/IAE.0000000000002819DOI Listing
February 2021

Intraocular schwannoma with extrascleral extension.

Eur J Ophthalmol 2020 Apr 28:1120672120920211. Epub 2020 Apr 28.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.

Purpose: To report a rare case of intraocular schwannoma with extrascleral extension in a patient with juvenile idiopathic arthritis and to review the literature for this topic.

Methods: Case report.

Results: A 19-year-old male with a history of juvenile idiopathic arthritis was referred for diagnosis and management of an episcleral mass, initially thought to be focal nodular scleritis. The ocular surface of the right eye revealed an elevated amelanotic episcleral nodule inferonasally, with thin strands of overlying sclera, feeding episcleral vessels, and measuring 11 mm × 11 mm in diameter and 5 mm in thickness. Ophthalmoscopic examination revealed a minimally pigmented ciliochoroidal tumor measuring 13 mm in diameter and 11.4 mm in total thickness and without associated subretinal fluid, orange pigment, or drusen. Ultrasound biomicroscopy and anterior-segment optical coherence tomography confirmed a solid mass with scleral disruption and extraocular extension. Shave biopsy revealed palisading spindle cells and interspersed eosinophilic fibrillary cytoplasmic processes, forming Verocay bodies. The specimen stained positive for S-100 and negative for Melan-A, consistent with benign schwannoma. Observation was recommended.

Conclusion: Intraocular schwannoma is a rare, benign uveal tumor that can demonstrate extrascleral extension, mimicking inflammatory and malignant neoplastic processes. Clinical diagnosis is challenging, and tissue biopsy is required for definite diagnosis.
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http://dx.doi.org/10.1177/1120672120920211DOI Listing
April 2020