Publications by authors named "Miguel A Materin"

63 Publications

Choroidal nevus with retinal invasion, clinical and imaging features.

Am J Ophthalmol Case Rep 2021 Jun 14;22:101059. Epub 2021 Mar 14.

Department of Ophthalmology, Duke University, Durham, NC, USA.

Purpose: To report a clinically challenging case of a choroidal nevus with retinal invasion with accompanying ancillary testing.

Observations: A 60-year-old Caucasian female was referred for a suspicious melanocytic choroidal lesion in her left eye. Ophthalmoscopic examination revealed a melanocytic choroidal lesion, measuring 10 mm × 10 mm in basal diameter. The lesion had a clinically evident area of retinal invasion seen as a protruding choroidal mass at its center, darker in appearance compared to the rest of the lesion, obscuring retinal vessels. The choroidal nevus had associated chronic retinal changes and the absence of overlying orange pigment or subretinal fluid. On fundus autofluorescence, there was a hypoautofluorescent area showing the site of retinal invasion. Fluorescein angiography at the lesion site exhibited central blocked perfusion corresponding to the area of retinal invasion. Ultrasonography showed a dome-shaped choroidal lesion that was optically dense with a medium-high internal reflectivity measuring 3.3mm in thickness. The optical coherence tomography showed a choroidal mass extruding through a break in Bruch's membrane with inner retinal invasion. A watchful waiting strategy was adopted, and at 28 months follow-up, the choroidal lesion did not show growth or presence of new suspicious features of malignant transformation.

Conclusion And Importance: This case highlights the importance of recognizing the key features of choroidal nevi with retinal invasion, which can prevent the treatment of a benign condition and assist in the arrival of a correct diagnosis. These lesions should be monitored for long-term.
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http://dx.doi.org/10.1016/j.ajoc.2021.101059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985462PMC
June 2021

Microvascular Features of Treated Retinoblastoma Tumors in Children Assessed Using OCTA.

Ophthalmic Surg Lasers Imaging Retina 2019 12;51(1):43-49

Background And Objective: To describe the microvascular features of treated, clinically regressed, or reactivated retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system.

Patients And Methods: Single-center, prospective, cross-sectional, consecutive case-series of children with previously treated retinoblastoma who underwent portable OCTA of posterior retinoblastoma lesions.

Results: Eight tumors from seven eyes of five children with retinoblastoma were included. Tumors with types 1 (calcified remnant, n = 3), 2 (non-calcified remnant, n = 1), and 3 (both calcified and noncalcified remnants, n = 1) regression revealed persistent intrinsic superficial vasculature on OCTA (five of five lesions; 100%). Lesions with type 4 regression (atrophic scar, n = 2) had complete vascular flow voids in the involved retina and underlying choriocapillaris. A reactivated tumor (n = 1) showed a distinct area of vascularity with prominent feeder/draining vessels.

Conclusions: OCTA revealed that significant vascularity exists in inactive retinoblastoma lesions. Dilated feeder vessels may suggest continued disease activity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:43-49.].
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http://dx.doi.org/10.3928/23258160-20191211-06DOI Listing
December 2019

HPV16-associated squamous cell carcinoma of the tongue metastatic to the ciliary body, iris, and lacrimal gland.

Can J Ophthalmol 2019 12 3;54(6):e294-e297. Epub 2019 Apr 3.

Department of Ophthalmology, University of North Carolina, Chapel Hill, N.C.. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2019.02.009DOI Listing
December 2019

Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography.

Ophthalmology 2019 12 15;126(12):1703-1711. Epub 2019 Jul 15.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Purpose: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA).

Design: Prospective cross-sectional study.

Participants: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center.

Methods: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes.

Main Outcome Measures: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC.

Results: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00).

Conclusions: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.
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http://dx.doi.org/10.1016/j.ophtha.2019.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875602PMC
December 2019

A Translucent Cystic Iris Lesion.

JAMA Ophthalmol 2019 Jun 20. Epub 2019 Jun 20.

Duke Eye Center, Department of Ophthalmology, Duke University, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.1651DOI Listing
June 2019

Vascular Findings in a Small Retinoblastoma Tumor Using OCT Angiography.

Ophthalmol Retina 2019 02 29;3(2):194-195. Epub 2018 Sep 29.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2018.09.018DOI Listing
February 2019

Imaging Infant Retinal Vasculature with OCT Angiography.

Ophthalmol Retina 2019 01 26;3(1):95-96. Epub 2018 Jul 26.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2018.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816267PMC
January 2019

Ophthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series.

Ophthalmology 2019 07 6;126(7):1058-1062. Epub 2019 Feb 6.

Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut; Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2019.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933747PMC
July 2019

Successive Uveal Melanomas with Different Gene Expression Profiles in an Eye with Ocular Melanocytosis.

Ocul Oncol Pathol 2018 Jun 17;4(4):236-239. Epub 2018 Jan 17.

Department of Ophthalmology, Duke University, Durham, NC, USA.

Ocular melanocytosis portends a higher risk of uveal melanoma. Multifocal uveal melanoma has been described previously and has been associated with ocular melanocytosis. Historically, histopathology has been used to differentiate tumors; however, molecular profiling now allows for better prognostication and determination of metastatic risk. The present case describes a patient with ocular melanocytosis who developed two sequential uveal melanomas in the same eye separated by 4 years. The uveal melanoma-specific gene expression profile (GEP) testing for the first tumor was class 1A and the second tumor was class 2. While the first tumor had low metastatic risk, the second tumor had a higher risk of metastasis, demonstrating the importance of GEP testing in cases of multifocal disease.
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http://dx.doi.org/10.1159/000484937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322218PMC
June 2018

Hyperreflective Vitreous Opacities on Optical Coherence Tomography in a Patient With Bilateral Retinoblastoma.

Ophthalmic Surg Lasers Imaging Retina 2019 01;50(1):50-52

An investigational, portable spectral-domain optical coherence tomography (SD-OCT) unit revealed small hyperreflective opacities in both eyes of a patient with bilateral retinoblastoma. There was no evidence of vitreous seeding on ophthalmoscopy of either eye. Although the opacities may initially raise concern for potential vitreous seeding, this report suggests alternate potential etiologies for such opacities, which were also seen on imaging of a cohort of normal eyes in pediatric patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:50-52.].
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http://dx.doi.org/10.3928/23258160-20181212-08DOI Listing
January 2019

Acute Presentation of Mesectodermal Leiomyoma of the Ciliary Body.

Ocul Oncol Pathol 2017 Nov 21;3(4):304-309. Epub 2017 Apr 21.

Yale New Haven Hospital, New Haven, Connecticut, USA.

Purpose: We report a case of acutely presenting mesectodermal leiomyoma of the ciliary body in a 29-year-old female who reported waking up with swollen eyelids of the right eye and light-perception vision. The affected eye had elevated intraocular pressure, a flat anterior chamber, and a pale, round mass arising from the nasal ciliary body, invading the angle and protruding into the visual axis posterior to the lens. Within days, the visual acuity decreased to no light perception. The eye was enucleated.

Methods: The enucleated eye harbored a tumor arising from the ciliary body, measuring 18 mm in the greatest dimension. Spindled cells with fibrillary cytoplasmic processes suggested a neural origin though negative for S-100, Melan-A, and HMB-45. The cells stained strongly positive for smooth muscle actin and vimentin, leading to the diagnosis of mesectodermal leiomyoma of the ciliary body.

Results: We review the literature to expand upon the clinical findings, diagnostic methods, and histopathologic and immunohistochemistry characteristics of mesectodermal leiomyoma.

Conclusion: Leiomyoma must be in the differential diagnosis for ciliary body mass, especially in women of reproductive age. Diagnosis relies on histopathology and immunohistochemistry. The mechanism of acute symptom onset may be multifactorial. This case emphasizes the possibility of acute presentation of a rare, benign intraocular tumor.
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http://dx.doi.org/10.1159/000464466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757584PMC
November 2017

CHOROIDAL TUMOR BIOPSY: A Review of the Current State and a Glance Into Future Techniques.

Retina 2018 09;38 Suppl 1:S79-S87

Departments of Vitreoretinal and Macular diseases and Orbital and Ocular Oncology, Byers Eye Institute, Stanford University, Palo Alto, California.

Purpose: To review the indications for and the methods of obtaining biopsies in eyes with uveal melanoma. In addition, this review provides recommendations for avoiding biopsy-related complications and discusses the future directions of biopsy techniques for uveal melanoma.

Methods: This review is based on a presentation by the authors (PM and MM) at the 2017 Duke Advanced Vitreoretinal Surgery Course and an extensive literature review using PubMed.

Results: Transscleral and transvitreal fine-needle aspiration biopsy, and transvitreal vitrectomy-assisted biopsy techniques are described. The use of 25- and 27-gauge needles and vitreous cutters through a transvitreal approach are most commonly used. Complications are uncommon but may include vitreous hemorrhage, retinal detachment, and rarely, extraocular extension. Proper technique and precautions will minimize the occurrence of these rare complications.

Conclusion: Biopsy of uveal melanoma either using a needle or vitrectomy-assisted procedures is safe and these techniques continue to improve with new vitreoretinal surgical advances.
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http://dx.doi.org/10.1097/IAE.0000000000001997DOI Listing
September 2018

A 71-year-old woman with decreased vision, nyctalopia, and peripheral vision loss.

Digit J Ophthalmol 2016;22(4):85-90. Epub 2016 Dec 31.

Department of Ophthalmology and Visual Science, Yale University, New Haven, Connecticut.

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http://dx.doi.org/10.5693/djo.02.2016.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596905PMC
June 2018

Venous Loop Reveals an Occult Retinoblastoma Tumor.

Ophthalmic Surg Lasers Imaging Retina 2017 09;48(9):768-770

A 14-day-old girl presented with bilateral hereditary retinoblastoma. At 3 months, a slight bend in the superotemporal arcade was observed to have developed into a venous loop. With concern for an occult lesion along the arcade, handheld optical coherence tomography (hhOCT) confirmed a small tumor and helped to guide prompt laser treatment while sparing the venous arcade. A venous loop is a previously unrecognized clinical finding that preceded the clinical detection and hhOCT confirmation of the tumor. The authors hypothesize that the venous loop was induced by pro-angiogenic factors secreted by the tumor. Portable hhOCT is a valuable adjunct imaging modality in the diagnosis and management of small retinoblastoma tumors. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:768-770.].
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http://dx.doi.org/10.3928/23258160-20170829-14DOI Listing
September 2017

An international survey of classification and treatment choices for group D retinoblastoma.

Int J Ophthalmol 2017 18;10(6):961-967. Epub 2017 Jun 18.

Ophthalmology Service, Hospital Infantil de Mexico Federico Gomez, Mexico City 01020, Mexico.

Aim: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region.

Methods: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism.

Results: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children's Hospital of Los Angeles (CHLA) version, 33% used the Children's Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (<0.0001).

Conclusion: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.
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http://dx.doi.org/10.18240/ijo.2017.06.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515152PMC
June 2017

Anterior Chamber Non-Hodgkin Lymphoma of the Iris Masquerading as Uveitis-Glaucoma-Hyphema Syndrome.

Ocul Oncol Pathol 2016 Oct 12;2(4):230-233. Epub 2016 May 12.

Department of Ophthalmology and Visual Science, New Haven, Conn., USA; Department of Ophthalmic Oncology, Smilow Cancer Hospital, New Haven, Conn., USA.

Purpose: To report a case of iris non-Hodgkin lymphoma initially thought to be uveitis-glaucoma-hyphema (UGH) syndrome.

Methods: We reviewed the clinical, radiographic, and histopathologic findings in a patient with recurrent hyphemas and increased ocular pressure who eventually was found to have a rapidly growing iris mass.

Results: An 89-year-old man with a history of cataract extraction and mantle cell lymphoma developed recurrent hyphema, which was subsequently revealed to be due to an iris mass. A biopsy revealed non-Hodgkin lymphoma that could not be formally subclassified but was suspicious for mantle cell lymphoma. The tumor showed a partial response to ibrutinib.

Conclusion: Iris lymphoma can masquerade as a cause of recurrent hyphema after cataract extraction. Ophthalmologists should be aware of this presentation, especially in patients with a history of lymphoma.
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http://dx.doi.org/10.1159/000445119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091236PMC
October 2016

NCCN Guidelines Insights: Melanoma, Version 3.2016.

J Natl Compr Canc Netw 2016 08;14(8):945-58

From Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; UCSF Helen Diller Family Comprehensive Cancer Center; Huntsman Cancer Institute at the University of Utah; University of Michigan Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; UC San Diego Moores Cancer Center; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The University of Tennessee Health Science Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; University of Colorado Cancer Center; Aim at Melanoma; Vanderbilt-Ingram Cancer Center; Mayo Clinic Cancer Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Yale Cancer Center/Smilow Cancer Hospital; Fox Chase Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; The University of Texas MD Anderson Cancer Center; Duke Cancer Institute; Roswell Park Cancer Institute; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; Moffitt Cancer Center; City of Hope Comprehensive Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network.

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.
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http://dx.doi.org/10.6004/jnccn.2016.0101DOI Listing
August 2016

Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2016 Apr;14(4):450-73

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.
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http://dx.doi.org/10.6004/jnccn.2016.0051DOI Listing
April 2016

BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION: A CASE REPORT.

Retin Cases Brief Rep 2017 Winter;11(1):71-74

*Department of Ophthalmology, Ophthalmic Oncology Program, Smilow Cancer Hospital at Yale New Haven, Yale University School of Medicine, New Haven, Connecticut; and †Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.

Purpose: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) in the setting of metastatic ovarian cancer.

Methods: In this observational case report, a 59-year-old woman presented with bilateral worsening vision and photophobia. She had been diagnosed with metastatic ovarian cancer 5 years prior for which she received Tamoxifen. Ophthalmic examination was completed followed by fluorescein angiography and optical coherence tomography (Spectralis OCT; Heidelberg Engineering).

Results: The visual acuity was 20/150 in both eyes. Exam demonstrated an iris pigmented lesion in the right eye, bilateral nuclear sclerotic cataracts, multiple orange lesions in the fundus, elevated pigmented uveal melanocytic tumors with diffuse choroidal thickening and multifocal early hyperfluorescence of these lesions (giraffe-like pattern) on fluorescein angiography, and exudative retinal detachment on OCT. The patient was diagnosed with BDUMP in the setting of metastatic ovarian carcinoma. Further metastatic workup demonstrated enlarged lymphadenopathy in the right axilla and inguinal regions. The patient declined chemotherapy and was initiated on plasmapheresis.

Conclusions: BDUMP is a peculiar paraneoplastic syndrome in the setting of metastatic ovarian cancer, where antigens from the retinal pigment epithelium, iris and choroidal melanocytes cross-react with ovarian tumor cell antibodies that are circulating in the serum. Plasmapheresis can decrease the concentrations of the antibodies, maintain reasonable functional vision and improve the quality of life.
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http://dx.doi.org/10.1097/ICB.0000000000000292DOI Listing
April 2017

Cyclosporine for Dry Eye Associated With Nivolumab: A Case Progressing to Corneal Perforation.

Cornea 2016 Mar;35(3):399-401

*Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT; and †Department of Internal Medicine, Yale School of Medicine, Smilow Cancer Hospital at Yale-New Haven Hospital, New Haven, CT.

Purpose: To present the clinical outcome of 2 cases of severe dry eye associated with Nivolumab, with 1 case progressing to corneal perforation.

Design: Case report.

Case 1: : A 58-year-old man with metastatic melanoma was referred for the management of severe bilateral dry eyes after undergoing his sixth cycle of Nivolumab. The right eye progressed to corneal perforation 4 weeks after referral, after which Nivolumab was discontinued. When metastatic disease recurred, Nivolumab was continued with an ocular surface stabilized with an intensive regimen that included topical cyclosporine.

Case 2: : A 46-year-old woman with metastatic melanoma was referred for severe dry eye symptoms around the timing of her third cycle of Nivolumab. Improvement of symptoms and surface staining was achieved with a regimen that included aggressive lubrication and topical cyclosporine. On follow-up after completing Nivolumab therapy, metastatic melanoma has remained regressed.

Conclusions: Nivolumab can cause or worsen dry eye disease to the point of corneal perforation. Given that its antitumor effect is immune-mediated, therapies targeting ocular surface inflammation can be effective for stabilizing dry eye disease in patients who continue treatment with Nivolumab.
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http://dx.doi.org/10.1097/ICO.0000000000000724DOI Listing
March 2016

Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.

Ophthalmic Plast Reconstr Surg 2017 Jan/Feb;33(1):e21-e23

*Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut; †Morgenstern Center for Orbital and Facial Plastic Surgery, Wayne, Pennsylvania; ‡Oculofacial Plastic Surgeons of Georgia, Atlanta, Georgia; and §Department of Ophthalmic Oncology, Smilow Cancer Hospital, Yale University School of Medicine, New Haven, Connecticut, U.S.A.

Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.
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http://dx.doi.org/10.1097/IOP.0000000000000432DOI Listing
March 2017

Clinical and histologic findings in patients with uveal melanomas after taking tumor necrosis factor-α inhibitors.

Mayo Clin Proc 2014 Nov 3;89(11):1481-6. Epub 2014 Nov 3.

Department of Ophthalmology, Mayo Clinic, Rochester, MN; Department of Molecular Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To describe the progression of uveal melanocytic lesions to melanomas after initiation of tumor necrosis factor-α (TNF-α) inhibitors.

Patients And Methods: We report 3 cases of uveal melanoma occurring after treatment with TNF-α inhibitors, 2 from Mayo Clinic and 1 from Yale University. The study took place from February 27, 2009, through July 15, 2013.

Results: Two women and one man with inflammatory disease who received TNF-α inhibitors had subsequent development of uveal melanomas. The 2 women had inflammatory bowel disease and had been followed up for melanocytic tumors that grew markedly within 1 year after beginning treatment with TNF-α inhibitors to the point of requiring treatment. One had histologic confirmation of the melanoma. The male patient had rheumatoid arthritis that was being treated with TNF-α inhibitors. Serial ultrasonography was performed to monitor bilateral diffuse scleritis, and within 16 months of initiation of TNF-α inhibitor therapy, a choroidal mass was detected that continued to grow over the next 3 months. The patient elected to have enucleation, which revealed uveal melanoma and thinning of the sclera from the previous scleritis.

Conclusion: Our 3 cases of uveal melanocytic tumors occurring after the use of TNF-α inhibitors add to the growing literature suggesting a correlation between TNF-α inhibitors and the development of malignant neoplasms. Considering the association between cutaneous melanoma and TNF-α inhibitors, we recommend that patients have an eye examination before initiation of TNF-α inhibitors, and those with preexisting nevi should be followed up at regular intervals.
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http://dx.doi.org/10.1016/j.mayocp.2014.08.012DOI Listing
November 2014

Verification of supraselective drug delivery for retinoblastoma using intra-arterial gadolinium.

J Neurointerv Surg 2013 Nov 27;5(6):e42. Epub 2012 Nov 27.

Department of Ophthalmology and Visual Sciences, Yale School of Medicine, New Haven, Connecticut, USA.

We present a description of retinoblastoma treated with supraselective intra-arterial chemotherapy, demonstrating selective delivery of the infused chemotherapeutic agent into the tumor bed by MRI. A 7-month-old presented with group E (international classification) unilateral retinoblastoma. We treated the patient with several rounds of intra-ophthalmic artery melphalan. Gadolinium was infused along with melphalan to visualize the distribution of this chemotherapeutic drug. Intraoperative MRI was obtained within 15 min after treatment and showed increased enhancement of the tumor and subretinal space. We demonstrate here that supraselective administration of chemotherapy into the ophthalmic artery appears to result in drug delivery to the tumor and subretinal space.
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http://dx.doi.org/10.1136/neurintsurg-2012-010508.repDOI Listing
November 2013

Verification of supraselective drug delivery for retinoblastoma using intra-arterial gadolinium.

BMJ Case Rep 2012 Nov 15;2012. Epub 2012 Nov 15.

Department of Ophthalmology and Visual Sciences, Yale School of Medicine, New Haven, Connecticut, USA.

We present a description of retinoblastoma treated with supraselective intra-arterial chemotherapy, demonstrating selective delivery of the infused chemotherapeutic agent into the tumor bed by MRI. A 7-month-old presented with group E (international classification) unilateral retinoblastoma. We treated the patient with several rounds of intra-ophthalmic artery melphalan. Gadolinium was infused along with melphalan to visualize the distribution of this chemotherapeutic drug. Intraoperative MRI was obtained within 15 min after treatment and showed increased enhancement of the tumor and subretinal space. We demonstrate here that supraselective administration of chemotherapy into the ophthalmic artery appears to result in drug delivery to the tumor and subretinal space.
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http://dx.doi.org/10.1136/bcr-2012-010508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545047PMC
November 2012

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.

Nat Genet 2012 Sep 29;44(9):1006-14. Epub 2012 Jul 29.

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1(P29S)) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1(P29S) showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.
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http://dx.doi.org/10.1038/ng.2359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432702PMC
September 2012

Sector laser photocoagulation for the prevention of macular edema after plaque radiotherapy for uveal melanoma: a pilot study.

Retina 2012 Sep;32(8):1601-7

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

Objective: To investigate the role of sector laser photocoagulation for prevention of macular edema after plaque radiotherapy for uveal melanoma.

Methods: Noncomparative, pilot interventional case series. The main outcome measure was optical coherence tomography-evident macular edema.

Results: A total of 29 patients had sector laser photocoagulation (sector panretinal photocoagulation) and sub-Tenon triamcinolone injection. The median tumor thickness and base was 3.3 mm and 10.0 mm. The median radiation dose and rate to the macula was 2,944 cGy and 31.0 cGy/hour. At the 12-month and 24-months follow-up, cystoid macular edema was found in 17% and 24% of the sector panretinal photocoagulation group. There were no major side effects registered.

Conclusion: Sector panretinal photocoagulation in combination with sub-Tenon triamcinolone appears to show potential as a safe and beneficial intervention for the prevention of macular edema after plaque radiotherapy for uveal melanoma in this series.
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http://dx.doi.org/10.1097/IAE.0b013e3182437e70DOI Listing
September 2012

Ocular neoplastic disease.

Semin Ultrasound CT MR 2011 Feb;32(1):28-37

Department of Diagnostic Radiology, Yale New Haven Hospital, New Haven, CT, USA.

Ocular neoplasms, both primary and metastatic, may present with visual disturbance or vision loss and often are asymptomatic. Clinical ophthalmologic examination may demonstrate leukocoria, abnormal pupillary light reflex, or a mass lesion with or without retinal detachment or hemorrhage. Retinoblastoma in children and uveal melanoma and ocular metastases in adults are the most important ocular malignant neoplasms referred for imaging to aid with diagnosis and staging. Familiarity with their common imaging appearances, the common patterns of spread, and the diagnostic findings of greatest concern to the ocular oncologist will enhance accuracy of imaging interpretation. Clinical ophthalmologic examination and imaging using B-scan ultrasound, A-scan ultrasound, fluorescein angiography, computed tomography and magnetic resonance imaging have complementary roles in ocular tumor staging and treatment assessment.
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http://dx.doi.org/10.1053/j.sult.2010.12.001DOI Listing
February 2011

Small choroidal melanoma with monosomy 3.

Middle East Afr J Ophthalmol 2010 Jul;17(3):268-9

Department of Ocular Oncology Service, Wills Eye Institute, Philadelphia, PA, USA.

Purpose: To report a patient with small juxtapapillary choroidal melanoma with chromosome 3 monosomy treated with I(125) plaque and transpupillary thermotherapy (TTT). A 64-year-old Caucasian male presented with painless blurred vision of the left eye. Ocular examination disclosed a small juxtapapillary choroidal melanocytic tumor with overlying subretinal fluid and orange pigment. Ultrasound showed an elevated choroidal mass of 2 mm thickness with low reflectivity on A-scan and hollowness on B scan, consistent with a small choroidal melanoma. The patient was treated with plaque I(125) radiotherapy combined with one session of TTT. Genetic testing of the tumor cells obtained by fine needle aspiration biopsy showed chromosome 3 monosomy. At 1 year after treatment, the tumor was regressed with resolution of subretinal fluid and 20/40 visual acuity. A small choroidal melanoma can manifest monosomy of chromosome 3, a known predictive factor for the development of systemic metastasis.
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http://dx.doi.org/10.4103/0974-9233.65487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934721PMC
July 2010

Fundus autofluorescence and optical coherence tomography findings in choroidal melanocytic lesions.

Middle East Afr J Ophthalmol 2010 Jul;17(3):201-6

Ophthalmic Oncology Section, Department of Ophthalmology, Yale University School of Medicine, New Haven, CT, USA.

Purpose: To establish the characteristics of secondary retinal and retinal pigment epithelial (RPE) changes associated with the presence of choroidal melanoma and choroidal nevus as documented by optical coherence tomography (OCT) and fundus autofluorescence (FAF).

Materials And Methods: PubMed review of major English publications examining the correlation between clinical characteristics of choroidal melanoma and nevus with OCT and FAF findings.

Results: The intrinsic properties of choroidal melanoma, as well as overlying RPE changes, drusen, and lipofuscin are best characterized by FAF, while OCT is more sensitive for the identification of subretinal and intraretinal fluid as well as atrophy, degeneration, and photoreceptor loss in the neurosensory retina.

Conclusions: Secondary retinal changes associated with choroidal melanocytic lesions can be documented by OCT and FAF. OCT-evident changes are observed more often with choroidal melanoma than choroidal nevus. OCT is better suited to identify the overlying retinal detachment and edema, even before these findings are clinically apparent. FAF is most useful in documenting the presence of lipofuscin, a finding that represents one of the important criteria in differentiating small choroidal melanoma from benign choroidal nevus.
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http://dx.doi.org/10.4103/0974-9233.65489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934710PMC
July 2010