Purpose: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. Observations: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. Conclusion: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.
, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, Ademola-Popoola DS, Adio A, Afshar AR, Aggarwal P, Aghaji AE, Ahmad A, Akib MNR, Al Harby L, Al Ani MH, Alakbarova A, Portabella SA, Al-Badri SAF, Alcasabas APA, Al-Dahmash SA, Alejos A, Alemany-Rubio E, Alfa Bio AI, Alfonso Carreras Y, Al-Haddad C, Al-Hussaini HHY, Ali AM, Alia DB, Al-Jadiry MF, Al-Jumaly U, Alkatan HM, All-Eriksson C, Al-Mafrachi AARM, Almeida AA, Alsawidi KM, Al-Shaheen AASM, Al-Shammary EH, Amiruddin PO, Antonino R, Astbury NJ, Atalay HT, Atchaneeyasakul L-O, Atsiaya R, Attaseth T, Aung TH, Ayala S, Baizakova B, Balaguer J, Balayeva R, Balwierz W, Barranco H, Bascaran C, Beck Popovic M, Benavides R, Benmiloud S, Bennani Guebessi N, Berete RC, Berry JL, Bhaduri A, Bhat S, Biddulph SJ, Biewald EM, Bobrova N, Boehme M, Boldt HC, Bonanomi MTBC, Bornfeld N, Bouda GC, Bouguila H, Boumedane A, Brennan RC, Brichard BG, Buaboonnam J, Calderón-Sotelo P, Calle Jara DA, Camuglia JE, Cano MR, Capra M, Cassoux N, Castela G, Castillo L, Català-Mora J, Chantada GL, Chaudhry S, Chaugule SS, Chauhan A, Chawla B, Chernodrinska VS, Chiwanga FS, Chuluunbat T, Cieslik K, Cockcroft RL, Comsa C, Correa ZM, Correa Llano MG, Corson TW, Cowan-Lyn KE, Csóka M, Cui X, Da Gama IV, Dangboon W, Das A, Das S, Davanzo JM, Davidson A, De Potter P, Delgado KQ, Demirci H, Desjardins L, Diaz Coronado RY, Dimaras H, Dodgshun AJ, Donaldson C, Donato Macedo CR, Dragomir MD, Du Y, Du Bruyn M, Edison KS, Eka Sutyawan WI, El Kettani A, Elbahi AM, Elder JE, Elgalaly D, Elhaddad AM, Elhassan MAM, Elzembely MM, Essuman VA, Evina TGA, Fadoo Z, Fandiño AC, Faranoush M, Fasina O, Fernández DDPG, Fernández-Teijeiro A, Foster A, Frenkel S, Fu LD, Fuentes-Alabi SL, Gallie BL, Gandiwa M, Garcia JL, García Aldana D, Gassant PY, Geel JA, Ghassemi F, Girón AV, Gizachew Z, Goenz MA, Gold AS, Goldberg-Lavid M, Gole GA, Gomel N, Gonzalez E, Gonzalez Perez G, González-Rodríguez L, Garcia Pacheco HN, Graells J, Green L, Gregersen PA, Grigorovski NDAK, Guedenon KM, Gunasekera SD, Gündüz AK, Gupta H, Gupta S, Hadjistilianou T, Hamel P, Hamid SA, Hamzah N, Hansen ED, Harbour WJ, Hartnett EM, Hasanreisoglu M, Hassan S, Hassan S, Hederova S, Hernandez J, Hernandez LMC, Hessissen L, Hordofa DF, Huang LC, Hubbard GB, Hummlen M, Husakova K, Hussein Al-Janabi AN, Ida R, Ilic VR, Jairaj V, Jeeva I, Jenkinson H, Ji X, Jo DH, Johnson KP, Johnson WJ, Jones MM, Kabesha TAB, Kabore RL, Kaliki S, Kalinaki A, Kantar M, Kao L-Y, Kardava T, Kebudi R, Kepak T, Keren-Froim N, Khan ZJ, Khaqan HA, Khauv P, Kheir WJ, Khetan V, Khodabande A, Khotenashvili Z, Kim JW, Kim JH, Kiratli H, Kivelä TT, Klett A, Komba Palet JEK, Krivaitiene D, Kruger M, Kulvichit K, Kuntorini MW, Kyara A, Lachmann ES, Lam CPS, Lam GC, Larson SA, Latinovic S, Laurenti KD, Le BHA, Lecuona K, Leverant AA, Li C, Limbu B, Long QB, López JP, Lukamba RM, Lumbroso L, Luna-Fineman S, Lutfi D, Lysytsia L, Magrath GN, Mahajan A, Majeed AR, Maka E, Makan M, Makimbetov EK, Manda C, Martín Begue N, Mason L, Mason JO, Matende IO, Materin M, Mattosinho CCDS, Matua M, Mayet I, Mbumba FB, McKenzie JD, Medina-Sanson A, Mehrvar A, Mengesha AA, Menon V, Mercado GJVD, Mets MB, Midena E, Mishra DKC, Mndeme FG, Mohamedani AA, Mohammad MT, Moll AC, Montero MM, Morales RA, Moreira C, Mruthyunjaya P, Msina MS, Msukwa G, Mudaliar SS, Muma KI, Munier FL, Murgoi G, Murray TG, Musa KO, Mushtaq A, Mustak H, Muyen OM, Naidu G, Nair AG, Naumenko L, Ndoye Roth PA, Nency YM, Neroev V, Ngo H, Nieves RM, Nikitovic M, Nkanga ED, Nkumbe H, Nuruddin M, Nyaywa M, Obono-Obiang G, Oguego NC, Olechowski A, Oliver SCN, Osei-Bonsu P, Ossandon D, Paez-Escamilla MA, Pagarra H, Painter SL, Paintsil V, Paiva L, Pal BP, Palanivelu MS, Papyan R, Parrozzani R, Parulekar M, Pascual Morales CR, Paton KE, Pawinska-Wasikowska K, Pe'er J, Peña A, Peric S, Pham CTM, Philbert R, Plager DA, Pochop P, Polania RA, Polyakov VG, Pompe MT, Pons JJ, Prat D, Prom V, Purwanto I, Qadir AO, Qayyum S, Qian J, Rahman A, Rahman S, Rahmat J, Rajkarnikar P, Ramanjulu R, Ramasubramanian A, Ramirez-Ortiz MA, Raobela Léa, Rashid R, Reddy AM, Reich E, Renner LA, Reynders D, Ribadu D, Riheia MM, Ritter-Sovinz P, Rojanaporn D, Romero L, Roy SR, Saab RH, Saakyan S, Sabhan AH, Sagoo MS, Said AMA, Saiju R, Salas B, San Román Pacheco S, Sánchez GL, Sayalith P, Scanlan TA, Schefler AC, Schoeman J, Sedaghat A, Seregard S, Seth R, Shah AS, Shakoor SA, Sharma MK, Sherief ST, Shetye NG, Shields CL, Siddiqui SN, Sidi Cheikh S, Silva S, Singh AD, Singh N, Singh U, Singha P, Sitorus RS, Skalet AH, Soebagjo HD, Sorochynska T, Ssali G, Stacey AW, Staffieri SE, Stahl ED, Stathopoulos C, Stirn Kranjc B, Stones DK, Strahlendorf C, Suarez MEC, Sultana S, Sun X, Sundy M, Superstein R, Supriyadi E, Surukrattanaskul S, Suzuki S, Svojgr K, Sylla F, Tamamyan G, Tan D, Tandili A, Tarrillo Leiva FF, Tashvighi M, Tateshi B, Tehuteru ES, Teixeira LF, Teh KH, Theophile T, Toledano H, Trang DL, Traoré F, Trichaiyaporn S, Tuncer S, Tyau-Tyau H, Umar AB, Unal E, Uner OE, Urbak SF, Ushakova TL, Usmanov RH, Valeina S, van Hoefen Wijsard M, Varadisai A, Vasquez L, Vaughan LO, Veleva-Krasteva NV, Verma N, Victor AA, Viksnins M, Villacís Chafla EG, Vishnevskia-Dai V, Vora T, Wachtel AE, Wackernagel W, Waddell K, Wade PD, Wali AH, Wang Y-Z, Weiss A, Wilson MW, Wime ADC, Wiwatwongwana A, Wiwatwongwana D, Wolley Dod C, Wongwai P, Xiang D, Xiao Y, Yam JC, Yang H, Yanga JM, Yaqub MA, Yarovaya VA, Yarovoy AA, Ye H, Yousef YA, Yuliawati P, Zapata López AM, Zein E, Zhang C, Zhang Y, Zhao J, Zheng X, Zhilyaeva K, Zia N, Ziko OAO, Zondervan M, Bowman R. Global Retinoblastoma Presentation and Analysis by National Income Level. JAMA Oncol 2020;Abstract
Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.
Immunotherapy has significantly advanced the field of oncology in recent decades. Understanding normal immunosurveillance, as well as the ways in which tumor cells have evolved to evade it, has provided the knowledge for development of drugs that allow one's own immune system to target and destroy malignant cells (immunotherapy). Cutaneous malignancies are particularly sensitive to this class of drugs. In a very sensitive anatomic region such as the periocular tissue, where surgical excision may come with significant morbidity, this technology has had a strong impact in the successful treatment of historically challenging tumors.
PURPOSE: To provide an update summarizing the biologic pathways governing von Hippel-Lindau (VHL) disease pathogenesis and to provide an overview of systemic manifestations as well as screening recommendations. METHODS: A PubMed search of the English language literature was reviewed using the following search terms: von Hippel-Lindau, von Hippel-Lindau disease, and VHL. Of 6,696 publications, the most current and pertinent information related to the pathogenesis and systemic aspects of VHL disease were included in this review. RESULTS: von Hippel-Lindau disease is one of the most frequently occurring multisystem familial cancer syndromes. The disease results from germline mutation in the VHL tumor suppressor gene on the short arm of chromosome 3. Mutation in the VHL gene affects multiple cellular processes including transcriptional regulation, extracellular matrix formation, apoptosis, and, in particular, the cellular adaptive response to hypoxia. As a result, there is widespread development of vascular tumors affecting the retina, brain, and spine, as well as a spectrum of benign and malignant tumors and/or cysts in visceral organs. CONCLUSION: The ophthalmologist plays a key role in VHL disease diagnosis, as retinal hemangioblastoma is frequently the first disease manifestation. Screening guidelines for individuals with known VHL disease, and those at risk of VHL disease, help to ensure early detection of potentially vision-threatening and life-threatening disease.
Merkel cell carcinoma (MCC) is a rare, aggressive tumor of both epithelial and neuroendocrine origin that carries a mortality rate of up to 40%. MCC tumors typically present as painless, expanding nodules on the sun-exposed skin areas of older, white patients. Eyelid and periocular tumors comprise approximately 2.5% of all cases of MCC and may be mistaken for chalazia or basal cell carcinomas. Immunosuppression is a significant risk factor, particularly in solid-organ transplant recipients, patients with chronic lymphocytic leukemia, and patients with HIV. Sentinel lymph node biopsy is often employed for accurate staging of head and neck MCC. Treatment includes wide-local excision, commonly with the addition of radiotherapy for improved locoregional disease control. Historically, adjuvant chemotherapy had been reserved for metastatic disease, but immunotherapy and targeted chemotherapies are currently being investigated for use in primary disease. The clinical characteristics of all available published cases of eyelid MCC are summarized .
PURPOSE: A case of a small benign storiform fibrous tumor of the conjunctival substantia propria is described to clarify the category of fibrous histiocytoma. In addition, a comparison of the various spindle cell tumors of the conjunctival substantia propria is explored. METHODS: The patient underwent a complete tumor excision, and the specimen was analyzed by histopathologic and immunohistochemical investigations. RESULTS: A cellular mass, composed solely of spindle cells in a storiform pattern without a component of histiocytic cells, was found beneath an undisturbed nonkeratinizing squamous epithelium and was separated from the epithelium by a grenz zone of uninvolved collagen. The lesion was sharply demarcated but not encapsulated. The Masson trichrome stain revealed scant deposition of intercellular collagen. The reticulin stain displayed numerous and delicate wiry fibers between the tumor cells and encircling capillaries. The Alcian blue stain demonstrated faint positivity in the interstitium. Immunohistochemistry revealed positivity for vimentin, factor XIIIa, smooth muscle actin, CD10, and CD45. Negative stains were obtained for CD34, CD56, S100, desmin, and Ki67. CONCLUSIONS: The broad term of fibrous histiocytoma should be reserved for deep fibroblastic spindle cell tumors (e.g., those of the orbit) that display an aggressive behavior. More benign superficial spindle cell tumors of the dermis are now preferentially characterized as dermatofibromas. It is suggested that equally benign epibulbar tumors should no longer be designated as fibrous histiocytomas but rather as benign storiform fibrous tumors. Tumors completely composed of polygonal histiocytoid (epithelioid) cells that are CD34+ should be excluded from the benign storiform fibrous tumor category. Positive smooth muscle actin and factor XIIIa staining in conjunction with negative staining for CD34 and desmin in the current spindled tumor cells are findings consistent with those of cutaneous dermatofibromas. Both the epibulbar and dermal spindle cell lesions have displayed an indolent and nonaggressive behavior. Microscopically they contain a high proportion of dendrocytic stellate cells that are either factor XIIIa+ or XIIIa-. Given the anatomic differences between the dermis and conjunctiva, the term dermatofibroma is inappropriate for the current tumor; instead the term benign storiform fibrous tumor has been proposed for superficial tumors of the conjunctiva.
The 2018 Ocular Oncogenesis and Oncology Conference was held through a partnership of the Association for Research in Vision and Ophthalmology (ARVO) and the Champalimaud Foundation. Twenty-one experts from international ocular oncology centers, from the Champalimaud Clinical Centre and the Champalimaud Foundation Cancer Research Program, and from patient advocacy organizations, delivered lectures on subjects that ranged from global ocular oncology, to basic research in mechanisms of ocular malignancy, to clinical research in ocular cancers, and to anticipated future developments in the area. The scientific program of the conference covered a broad range of ocular tumors-including uveal melanoma, retinoblastoma, ocular surface tumors, and adnexal and intraocular lymphomas-and pathogenesis and management were deliberated in the context of the broader systemic cancer discipline. In considering the latest basic and clinical research developments in ocular oncogenesis and oncology, and providing the opportunity for cross-talk between ocular cancer biologists, systemic cancer biologists, ocular oncologists, systemic oncologists, patients, and patient advocates, the forum generated new knowledge and novel insights for the field. This report summarizes the content of the invited talks at the 2018 ARVO-Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.
An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.
PURPOSE: Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia. DESIGN: Retrospective case series. METHODS: Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion. RESULTS: PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100%) of the tumors expressed PD-L1: 7 (39%) expressed a high level, 3 (17%) expressed a medium level, and 8 (44%) expressed a low level. Only 9 (50%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P < .01) and with the presence of CD8-positive cells in the surrounding stroma (P = .04). CONCLUSIONS: A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.
Duffy DL, Zhu G, Li X, Sanna M, Iles MM, Jacobs LC, Evans DM, Yazar S, Beesley J, Law MH, Kraft P, Visconti A, Taylor JC, Liu F, Wright MJ, Henders AK, Bowdler L, Glass D, Ikram AM, Uitterlinden AG, Madden PA, Heath AC, Nelson EC, Green AC, Chanock S, Barrett JH, Brown MA, Hayward NK, Macgregor S, Sturm RA, Hewitt AW, Hewitt AW, Kayser M, Hunter DJ, Newton Bishop JA, Spector TD, Montgomery GW, Mackey DA, Smith GD, Nijsten TE, Bishop TD, Bataille V, Falchi M, Han J, Martin NG. Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways. Nat Commun 2019;10(1):299.Abstract
The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
PURPOSE: To describe outcomes of globe-preserving surgery combined with high-dose proton beam radiation (PBR) in treating primary adenoid cystic carcinoma (ACC) of the lacrimal gland. DESIGN: Retrospective case series. METHODS: Twenty-nine patients with primary ACC of the lacrimal gland were identified in the records of a single institution between 1990 and 2017. Patients with nonorbital primary tumor origins or with inadequate follow-ups were excluded. Eighteen patients met inclusion criteria. Clinical data, imaging studies, histopathology, treatment modality, local recurrences, visual outcomes, metastases, and survivals were assessed. Disease-free survivals for the current patients were measured and compared to those of other studies. RESULTS: The eighteen patients (14 female, 4 male) were followed for a median of 12.9 years (range 0.6-22.3 years) after treatment completion. Their median age was 40 years. Four were children (median age 12 years). All were treated with globe-preserving tumor resection and radiation (median dose of 72 cobalt gray equivalents). Three adult patients died of metastatic disease (median of 4.2 years after treatment). Four had local recurrences. Useful vision (20/40 or better) was retained for a median 3 years (range 1-12.9 years). Radiation morbidity included brain injury, retinopathy, optic neuropathy, keratopathy, and cataract. Overall and disease-free survivals were significantly better compared to historical treatments, but did not differ statistically from other modern approaches. CONCLUSIONS: Globe-preserving surgery with PBR, although imperfect, has a favorable long-term survival compared to other modern modalities, and offers a variable period of useful vision.