Abstract
The proliferation of targeted anticancer agents over the last two decades has revolutionized cancer treatment and improved survival in many previously refractory malignancies. However, many agents are associated with characteristic ophthalmic adverse effects. It is important that ophthalmologists recognize and maintain a high index of suspicion for these side effects in patients on targeted therapy. Most ophthalmic adverse effects can be treated with specific ocular therapy without discontinuation of cancer treatment, although it is important to be aware of the life-threatening and vision-threatening circumstances that would require therapy cessation in conjunction with the patient’s oncologist. This review aims to summarize the ophthalmic adverse effects of targeted and hormonal anticancer agents and briefly describe their management.
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Change history
15 February 2022
A Correction to this paper has been published: https://doi.org/10.1007/s40265-022-01686-3
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.
Rehman FU, Al-Waeel M, Naz SS, Shah KU. Anticancer therapeutics: a brief account on wide refinements. Am J Cancer Res. 2020;10(11):3599–621.
Dembic Z. Antitumor drugs and their targets. Molecules. 2020. https://doi.org/10.3390/molecules25235776.
Dalvin LA, Shields CL, Orloff M, Sato T, Shields JA. CHECKPOINT INHIBITOR IMMUNE THERAPY: systemic indications and ophthalmic side effects. Retina. 2018;38(6):1063–78. https://doi.org/10.1097/iae.0000000000002181.
Fortes BH, Liou H, Dalvin LA. Ophthalmic adverse effects of immune checkpoint inhibitors: the Mayo Clinic experience. Br J Ophthalmol. 2020. https://doi.org/10.1136/bjophthalmol-2020-316970.
Services USDoHaH. Common terminology criteria for adverse events (CTCAE). 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf. Accessed 24 Feb 2021.
Braicu B, Busuioc D, Gulei R, et al. A comprehensive review on MAPK: a promising therapeutic target in cancer. Cancers. 2019;11(10):1618. https://doi.org/10.3390/cancers11101618.
Novartis Pharmaceuticals Corporation. Mekinist (Trametinib) [Prescribing Information]. East Hanover: Novartis Pharmaceuticals Corporation; 2018.
Genentech USA, Inc. Cotellic (Cobimetinib) [Prescribing Information]. San Francisco: Genentech USA, Inc.; 2015.
AstraZeneca Pharmaceuticals LP. Koselugo (Selumetinib) [Prescribing Information]. Wilmington: AstraZeneca Pharmaceuticals LP; 2020.
Array BioPharma Inc.. Mektovi (Binimetinib) [Prescribing Information]. Boulder: Array BioPharma Inc.; 2018.
Méndez-Martínez S, Calvo P, Ruiz-Moreno O, Pardiñas Barón N, Leciñena Bueno J, Gil Ruiz MDR, et al. Ocular adverse events associated with MEK inhibitors. Retina. 2019;39(8):1435–50. https://doi.org/10.1097/iae.0000000000002451.
Stjepanovic N, Velazquez-Martin JP, Bedard PL. Ocular toxicities of MEK inhibitors and other targeted therapies. Ann Oncol. 2016;27(6):998–1005. https://doi.org/10.1093/annonc/mdw100.
de la Cruz-Merino L, Di Guardo L, Grob JJ, Venosa A, Larkin J, McArthur GA, et al. Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. J Transl Med. 2017;15(1):146. https://doi.org/10.1186/s12967-017-1246-0.
Urner-Bloch U, Urner M, Jaberg-Bentele N, Frauchiger AL, Dummer R, Goldinger SM. MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: long-term ophthalmic effects. Eur J Cancer. 2016;65:130–8. https://doi.org/10.1016/j.ejca.2016.06.018.
Urner-Bloch U, Urner M, Stieger P, Galliker N, Winterton N, Zubel A, et al. Transient MEK inhibitor-associated retinopathy in metastatic melanoma. Ann Oncol. 2014;25(7):1437–41. https://doi.org/10.1093/annonc/mdu169.
van Dijk EH, van Herpen CM, Marinkovic M, Haanen JB, Amundson D, Luyten GP, et al. Serous retinopathy associated with mitogen-activated protein kinase kinase inhibition (Binimetinib) for metastatic cutaneous and uveal melanoma. Ophthalmology. 2015;122(9):1907–16. https://doi.org/10.1016/j.ophtha.2015.05.027.
Weber ML, Liang MC, Flaherty KT, Heier JS. Subretinal fluid associated with MEK inhibitor use in the treatment of systemic cancer. JAMA Ophthalmol. 2016;134(8):855–62. https://doi.org/10.1001/jamaophthalmol.2016.0090.
Albertini GC, Corbelli E, Battaglia Parodi M, Bandello F. Choroidal neovascularization in multifocal choroiditis after dabrafenib and trametinib. Eur J Ophthalmol. 2017;27(6):e184–6. https://doi.org/10.5301/ejo.5001013.
Boutros A, Schiavi C, Cecchi F, Spagnolo F, Guadagno A, Tanda ET, et al. Case report: immune-related toxicity during adjuvant treatment with BRAF plus MEK inhibitors in a melanoma patient. Front Immunol. 2020;11:579523. https://doi.org/10.3389/fimmu.2020.579523.
Brambati M, Giuffrè C, Marchese A, Bandello F, Modorati GM, Miserocchi E. A case of Vogt-Koyanagi-Harada-like uveitis secondary to dabrafenib/trametinib therapy for advanced melanoma. Eur J Ophthalmol. 2020:1120672120962044. https://doi.org/10.1177/1120672120962044.
Diamantopoulos PT, Stoungioti S, Anastasopoulou A, Papaxoinis G, Gogas H. Incomplete Vogt–Koyanagi–Harada disease following treatment with encorafenib and binimetinib for metastatic melanoma. Melanoma Res. 2018;28(6):648–51. https://doi.org/10.1097/cmr.0000000000000505.
Draganova D, Kerger J, Caspers L, Willermain F. Severe bilateral panuveitis during melanoma treatment by Dabrafenib and Trametinib. J Ophthalmic Inflamm Infect. 2015;5:17. https://doi.org/10.1186/s12348-015-0049-9.
Fujimura T, Kambayashi Y, Tanita K, Sato Y, Hidaka T, Otsuka A, et al. HLA-DRB1*04:05 in two cases of Vogt-Koyanagi-Harada disease-like uveitis developing from an advanced melanoma patient treated by sequential administration of nivolumab and dabrafenib/trametinib therapy. J Dermatol. 2018;45(6):735–7. https://doi.org/10.1111/1346-8138.14273.
Joshi L, Karydis A, Gemenetzi M, Shao EH, Taylor SR. Uveitis as a result of MAP kinase pathway inhibition. Case Rep Ophthalmol. 2013;4(3):279–82. https://doi.org/10.1159/000357060.
Lim J, Lomax AJ, McNeil C, Harrisberg B. Uveitis and papillitis in the setting of dabrafenib and trametinib therapy for metastatic melanoma: a case report. Ocul Immunol Inflamm. 2018;26(4):628–31. https://doi.org/10.1080/09273948.2016.1246666.
Mozo Cuadrado M, Tabuenca Del Barrio L, Compains SE. Bilateral drug-induced uveitis and epiretinal membrane during the treatment of a metastatic cutaneous melanoma. Ocul Immunol Inflamm. 2019. https://doi.org/10.1080/09273948.2019.1685111.
Niro A, Recchimurzo N, Sborgia A, Guida M, Alessio G. Bilateral ischemic retinal vasculitis in metastatic cutaneous melanoma patient treated with dabrafenib and trametinib: a case report. Ocul Immunol Inflamm. 2018;26(5):783–5. https://doi.org/10.1080/09273948.2016.1261166.
Sarny S, Neumayer M, Kofler J, El-Shabrawi Y. Ocular toxicity due to trametinib and dabrafenib. BMC Ophthalmol. 2017;17(1):146. https://doi.org/10.1186/s12886-017-0541-0.
Genentech USA, Inc. Zelboraf (Vemurafenib) [Prescribing Information]. San Francisco: Genentech USA, Inc.; 2016.
Novartis Pharmaceuticals Corporation. Tafinlar (Dabrafenib) [Prescribing Information]. East Hanover: Novartis Pharmaceuticals Corporation; 2018.
Array BioPharma Inc. Braftovi (Encorafenib) [Prescribing Information]. Boulder: Array BioPharma Inc.; 2020.
Choe CH, McArthur GA, Caro I, Kempen JH, Amaravadi RK. Ocular toxicity in BRAF mutant cutaneous melanoma patients treated with vemurafenib. Am J Ophthalmol. 2014;158(4):831-7.e2. https://doi.org/10.1016/j.ajo.2014.07.003.
Agemy SA, Mehta AN, Pachydaki SI, Tewari A. Bilateral panuveitis in a patient on vemurafenib BRAF inhibitor therapy for stage IV melanoma. Eur J Ophthalmol. 2014;24(4):629–32. https://doi.org/10.5301/ejo.5000423.
Apivatthakakul A, Kunavisarut P, Rothova A, Pathanapitoon K. Development of Acute Vogt-Koyanagi-Harada-like syndrome during the treatment course with vemurafenib for metastatic melanoma. Ocul Immunol Inflamm. 2020;28(3):505–8. https://doi.org/10.1080/09273948.2019.1597896.
Eser Öztürk H, Süllü Y. Sarcoid-like granulomatous intraocular inflammation caused by vemurafenib treatment for metastatic melanoma. Turk J Ophthalmol. 2020;50(1):50–2. https://doi.org/10.4274/tjo.galenos.2019.79026.
Fusumae T, Kamiya K, Maekawa T, Komine M, Murata S, Inoda S, et al. Vogt-Koyanagi-Harada disease-like uveitis induced by vemurafenib for metastatic cutaneous malignant melanoma. J Dermatol. 2018;45(6):e159–60. https://doi.org/10.1111/1346-8138.14200.
Guedj M, Quéant A, Funck-Brentano E, Kramkimel N, Lellouch J, Monnet D, et al. Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib. JAMA Ophthalmol. 2014;132(12):1421–5. https://doi.org/10.1001/jamaophthalmol.2014.3024.
Sızmaz S, Görkemli N, Esen E, Demircan N. A rare cause of uveitis: vemurafenib. Turk J Ophthalmol. 2018;48(6):323–5. https://doi.org/10.4274/tjo.95914.
Wolf SE, Meenken C, Moll AC, Haanen JB, van der Heijden MS. Severe pan-uveitis in a patient treated with vemurafenib for metastatic melanoma. BMC Cancer. 2013;13:561. https://doi.org/10.1186/1471-2407-13-561.
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30–9. https://doi.org/10.1056/NEJMoa1412690.
Tyagi P, Santiago C. New features in MEK retinopathy. BMC Ophthalmol. 2018;18(Suppl 1):221. https://doi.org/10.1186/s12886-018-0861-8.
Anforth R, Fernandez-Peñas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. 2013;14(1):e11–8. https://doi.org/10.1016/s1470-2045(12)70413-8.
Yin VT, Wiraszka TA, Tetzlaff M, Curry JL, Esmaeli B. Cutaneous eyelid neoplasms as a toxicity of vemurafenib therapy. Ophthalmic Plast Reconstr Surg. 2015;31(4):e112–5. https://doi.org/10.1097/iop.0000000000000140.
Torres-Navarro I, de Unamuno-Bustos B, Botella-Estrada R. Systematic review of BRAF/MEK inhibitors-induced severe cutaneous adverse reactions (SCARs). J Eur Acad Dermatol Venereol. 2020. https://doi.org/10.1111/jdv.16894.
Bristol-Myers Squibb Company. Yervoy (Ipilimumab) Injection [Prescribing Information]. Princeton: Bristol-Myers Squibb Company; 2020.
Merck & Company Inc. Keytruda (Pembrolizumab) for Injection [Prescribing Information]. Whitehouse Station: Merck & Co, Inc; 2020.
Bristol-Myers Squibb Company. Opdivo (Nivolumab) Injection [Prescribing Information]. Princeton: Bristol-Myers Squibb Company; 2020.
Genentech Inc. Tecentriq (Atezolizumab) Injection [Prescribing Information]. South San Francisco: Genentech, Inc; 2019.
EMD Serono Inc. Bavencio (Avelumab) Injection, for Intravenous Use [Prescribing Information]. Rockland: EMD Serono, Inc and Pfizer, Inc; 2019.
AstraZeneca Pharmaceuticals LP. Imfinzi (Durvalumab) Injection, for Intravenous Use [Prescribing Information]. Wilmington: AstraZeneca Pharmaceuticals LP; 2020.
Regeneron. Libtayo (Cemiplimab) Injection [Prescribing Information]. Tarrytown: Regeneron 2020.
Abdel-Rahman O, Oweira H, Petrausch U, Helbling D, Schmidt J, Mannhart M, et al. Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review. Expert Rev Anticancer Ther. 2017;17(4):387–94. https://doi.org/10.1080/14737140.2017.1296765.
Cappelli LC, Gutierrez AK, Bingham CO 3rd, Shah AA. Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature. Arthritis Care Res (Hoboken). 2017;69(11):1751–63. https://doi.org/10.1002/acr.23177.
Gibney GT, Kudchadkar RR, DeConti RC, Thebeau MS, Czupryn MP, Tetteh L, et al. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin Cancer Res. 2015;21(4):712–20. https://doi.org/10.1158/1078-0432.Ccr-14-2468.
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–44. https://doi.org/10.1056/NEJMoa1305133.
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50. https://doi.org/10.1016/s0140-6736(15)01281-7.
Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, et al. Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res. 2014;2(7):632–42. https://doi.org/10.1158/2326-6066.Cir-14-0053.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32. https://doi.org/10.1056/NEJMoa1503093.
Weber J, Gibney G, Kudchadkar R, Yu B, Cheng P, Martinez AJ, et al. Phase I/II study of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab. Cancer Immunol Res. 2016;4(4):345–53. https://doi.org/10.1158/2326-6066.Cir-15-0193.
Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691–7. https://doi.org/10.1200/jco.2012.41.6750.
Zimmer L, Vaubel J, Mohr P, Hauschild A, Utikal J, Simon J, et al. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma. PLoS ONE. 2015;10(3):e0118564. https://doi.org/10.1371/journal.pone.0118564.
Baughman DM, Lee CS, Snydsman BE, Jung HC. Bilateral uveitis and keratitis following nivolumab treatment for metastatic melanoma. Med Case Rep (Wilmington). 2017. https://doi.org/10.21767/2471-8041.100044.
Kim JM, Materin MA, Sznol M, Kluger HM, Weiss S, Chow J, et al. Ophthalmic immune-related adverse events of immunotherapy: a single-site case series. Ophthalmology. 2019;126(7):1058–62. https://doi.org/10.1016/j.ophtha.2019.01.031.
Le Fournis S, Gohier P, Urban T, Jeanfaivre T, Hureaux J. Corneal graft rejection in a patient treated with nivolumab for primary lung cancer. Lung Cancer. 2016;102:28–9. https://doi.org/10.1016/j.lungcan.2016.10.008.
Losonczy G, Gijs M, Nuijts R. Nivolumab-induced ulcerative keratitis-a case report. Cornea. 2020. https://doi.org/10.1097/ico.0000000000002460.
Nguyen AT, Elia M, Materin MA, Sznol M, Chow J. Cyclosporine for dry eye associated with nivolumab: a case progressing to corneal perforation. Cornea. 2016;35(3):399–401. https://doi.org/10.1097/ico.0000000000000724.
Oh JY. Autoimmune keratitis after atezolizumab treatment. N Engl J Med. 2020;383(15):1468. https://doi.org/10.1056/NEJMicm1910925.
Papavasileiou E, Prasad S, Freitag SK, Sobrin L, Lobo AM. Ipilimumab-induced ocular and orbital inflammation–a case series and review of the literature. Ocul Immunol Inflamm. 2016;24(2):140–6. https://doi.org/10.3109/09273948.2014.1001858.
Parker JS, Feagin W, Wang C, Heersink M, Parker JS. Corneal ulceration associated with nivolumab use. Am J Ophthalmol Case Rep. 2019;14:26–7. https://doi.org/10.1016/j.ajoc.2019.01.013.
Vanhonsebrouck E, Van De Walle M, Lybaert W, Kruse V, Roels D. Bilateral corneal graft rejection associated with pembrolizumab treatment. Cornea. 2020;39(11):1436–8. https://doi.org/10.1097/ico.0000000000002372.
Voskens C, Cavallaro A, Erdmann M, Dippel O, Kaempgen E, Schuler G, et al. Anti-cytotoxic T-cell lymphocyte antigen-4-induced regression of spinal cord metastases in association with renal failure, atypical pneumonia, vision loss, and hearing loss. J Clin Oncol. 2012;30(33):e356–7. https://doi.org/10.1200/jco.2011.41.4359.
Weng CC, Wu CC, Lin PY. Corneal melting in a case undergoing treatment with pembrolizumab. Clin Exp Optom. 2020;103(3):379–81. https://doi.org/10.1111/cxo.12973.
Bitton K, Michot JM, Barreau E, Lambotte O, Haigh O, Marabelle A, et al. Prevalence and clinical patterns of ocular complications associated with anti-PD-1/PD-L1 anticancer immunotherapy. Am J Ophthalmol. 2019;202:109–17. https://doi.org/10.1016/j.ajo.2019.02.012.
Andrade RA, Moll-Udina A, Martin R, Cilveti E, Subirà O, Disfetano L, et al. Retinal vasculitis secondary to durvalumab. Case Rep Ophthalmol. 2020;11(2):161–6. https://doi.org/10.1159/000507609.
Aaberg MT, Aaberg TM Jr. Pembrolizumab administration associated with posterior uveitis. Retin Cases Brief Rep. 2017;11(4):348–51. https://doi.org/10.1097/icb.0000000000000368.
Abu Samra K, Valdes-Navarro M, Lee S, Swan R, Foster CS, Anesi SD. A case of bilateral uveitis and papillitis in a patient treated with pembrolizumab. Eur J Ophthalmol. 2016;26(3):e46–8. https://doi.org/10.5301/ejo.5000724.
Conrady CD, Larochelle M, Pecen P, Palestine A, Shakoor A, Singh A. Checkpoint inhibitor-induced uveitis: a case series. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):187–91. https://doi.org/10.1007/s00417-017-3835-2.
Dow ER, Yung M, Tsui E. Immune checkpoint inhibitor-associated uveitis: review of treatments and outcomes. Ocul Immunol Inflamm. 2020. https://doi.org/10.1080/09273948.2020.1781902.
Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12. https://doi.org/10.1016/s1470-2045(14)70189-5.
Manusow JS, Khoja L, Pesin N, Joshua AM, Mandelcorn ED. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma. J Immunother Cancer. 2014;2(1):41. https://doi.org/10.1186/s40425-014-0041-1.
Moorthy RS, Moorthy MS, Cunningham ET Jr. Drug-induced uveitis. Curr Opin Ophthalmol. 2018;29(6):588–603. https://doi.org/10.1097/icu.0000000000000530.
Numata S, Iwata Y, Okumura R, Arima M, Kobayashi T, Watanabe S, et al. Bilateral anterior uveitis and unilateral facial palsy due to ipilimumab for metastatic melanoma in an individual with human leukocyte antigen DR4: a case report. J Dermatol. 2018;45(1):113–4. https://doi.org/10.1111/1346-8138.13779.
Parikh RA, Chaon BC, Berkenstock MK. Ocular complications of checkpoint inhibitors and immunotherapeutic agents: a case series. Ocul Immunol Inflamm. 2020. https://doi.org/10.1080/09273948.2020.1766082.
Sun MMP, Levinson RM, Filipowicz AD, Anesi SM, Kaplan HM, Wang WMP, et al. Uveitis in patients treated with CTLA-4 and PD-1 checkpoint blockade inhibition. Ocul Immunol Inflamm. 2020;28(2):217–27. https://doi.org/10.1080/09273948.2019.1577978.
Tsui E, Madu A, Belinsky I, Yannuzzi LA, Freund KB, Modi YS. Combination ipilimumab and nivolumab for metastatic melanoma associated with ciliochoroidal effusion and exudative retinal detachment. JAMA Ophthalmol. 2017;135(12):1455–7. https://doi.org/10.1001/jamaophthalmol.2017.4872.
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33. https://doi.org/10.1056/NEJMoa1302369.
Yu CW, Yau M, Mezey N, Joarder I, Micieli JA. Neuro-ophthalmic complications of immune checkpoint inhibitors: a systematic review. Eye Brain. 2020;12:139–67. https://doi.org/10.2147/eb.S277760.
Betrains A, Blockmans DE. Immune checkpoint inhibitor-associated polymyalgia rheumatica/giant cell arteritis occurring in a patient after treatment with nivolumab. J Clin Rheumatol. 2019. https://doi.org/10.1097/rhu.0000000000001012.
Goldstein BL, Gedmintas L, Todd DJ. Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4. Arthritis Rheumatol. 2014;66(3):768–9. https://doi.org/10.1002/art.38282.
Chow KL, Perju-Dumbrava L, Malhotra A, Olesen I, Briggs P. Giant cell arteritis secondary to combined nivolumab and ipilimumab in metastatic pleural mesothelioma. Neurol Asia. 2020;25(1):87–8.
Micaily I, Chernoff M. An unknown reaction to pembrolizumab: giant cell arteritis. Ann Oncol. 2017;28(10):2621–2. https://doi.org/10.1093/annonc/mdx306.
Narala R, Reddy SA, Mruthyunjaya P. Giant cell arteritis manifesting as retinal arterial occlusion and paracentral acute middle maculopathy in a patient on pembrolizumab for metastatic uveal melanoma. Am J Ophthalmol Case Rep. 2020;20:100891. https://doi.org/10.1016/j.ajoc.2020.100891.
Touat M, Maisonobe T, Knauss S, Ben Hadj Salem O, Hervier B, Auré K et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology. 2018;91(10):e985–94. https://doi.org/10.1212/wnl.0000000000006124.
Maloney NJ, Ravi V, Cheng K, Bach DQ, Worswick S. Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review. Int J Dermatol. 2020;59(6):e183–8. https://doi.org/10.1111/ijd.14811.
Tremont A, Lu J, Cole JT. Endocrine therapy for early breast cancer: updated review. Ochsner J. 2017;17(4):405–11.
Krauss K, Stickeler E. Endocrine therapy in early breast cancer. Breast Care. 2020;15(4):337–46. https://doi.org/10.1159/000509362.
An KC. Selective estrogen receptor modulators. Asian Spine J. 2016;10(4):787–91. https://doi.org/10.4184/asj.2016.10.4.787.
Midatech Pharma US Inc. Soltamox (Tamoxifen) [Prescribing Information]. Raleigh: Midatech Pharma US Inc; 2018.
Eli Lilly and Company. Evista (Raloxifene) [Prescribing Information]. Indianapolis: Eli Lilly and Company; 2020.
Kyowa Kirin Inc. Fareston (Toremifene) [Prescribing Information]. Bedminster: Kyowa Kirin Inc; 2017.
Dulley P. Ocular adverse reactions to tamoxifen–a review. Ophthalmic Physiol Opt. 1999;19(Suppl 1):S2-9. https://doi.org/10.1016/s0275-5408(98)00084-2.
Noureddin BN, Seoud M, Bashshur Z, Salem Z, Shamseddin A, Khalil A. Ocular toxicity in low-dose tamoxifen: a prospective study. Eye (Lond). 1999;13(Pt 6):729–33. https://doi.org/10.1038/eye.1999.217.
Pavlidis NA, Petris C, Briassoulis E, Klouvas G, Psilas C, Rempapis J et al. Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients. Cancer. 1992;69(12):2961-4. https://doi.org/10.1002/1097-0142(19920615)69:12<2961::aid-cncr2820691215>3.0.co;2-w.
Muftuoglu O, Uçakhan OO, Kanpolat A. Clinical and in vivo confocal microscopy findings in patients receiving tamoxifen citrate. Eye Contact Lens. 2006;32(5):228–32. https://doi.org/10.1097/01.icl.0000201396.74294.85.
Tang R, Shields J, Schiffman J, Li H, Locher D, Hampton J, et al. Retinal changes associated with tamoxifen treatment for breast cancer. Eye (Lond). 1997;11(Pt 3):295–7. https://doi.org/10.1038/eye.1997.64.
Kim HA, Lee S, Eah KS, Yoon YH. Prevalence and risk factors of tamoxifen retinopathy. Ophthalmology. 2020;127(4):555–7. https://doi.org/10.1016/j.ophtha.2019.10.038.
Demirci NS, Erdem GU, Uçgun N, Bozkaya Y, Ozdemir NY, Dogan M, et al. A rare case: branch retinal vein occlusion associated with the use of tamoxifen. J Cancer Res Ther. 2019;15(3):722–4. https://doi.org/10.4103/0973-1482.204888.
Onder H, Kilic AC, Kose SA, Karatas A, Kaya E, Kaya M, et al. Branch retinal vein occlusion associated with tamoxifen use. Semin Ophthalmol. 2013;28(2):88–90. https://doi.org/10.3109/08820538.2012.760618.
Gorin MB, Day R, Costantino JP, Fisher B, Redmond CK, Wickerham L, et al. Long-term tamoxifen citrate use and potential ocular toxicity. Am J Ophthalmol. 1998;125(4):493–501. https://doi.org/10.1016/s0002-9394(99)80190-1.
Parkkari M, Paakkala AM, Salminen L, Holli K. Ocular side-effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow-up study. Acta Ophthalmol Scand. 2003;81(5):495–9. https://doi.org/10.1034/j.1600-0420.2003.00116.x.
AstraZeneca Pharmaceuticals LP. Faslodex (Fulvestrant) [Prescribing Information]. Wilmington: AstraZeneca Pharmaceuticals LP; 2020.
Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299-309. https://doi.org/10.1093/jnci/djr242.
(EBCTCG) EBCTCG. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–52. https://doi.org/10.1016/S0140-6736(15)61074-1.
AstraZenaca Pharmaceuticals LP. ARIMIDEX (Anastrozole) [Prescribing Information]. Wilmington: AstraZenaca Pharmaceuticals LP; 2020.
Novartis Pharmaceuticals Corporation. Femara (Letrozole) [Prescribing Information]. East Hanover: Novartis Pharmaceuticals Corporation; 2020.
Pharmacia & Upjohn Co. Aromasin (Exemestane) [Prescribing Information]. New York: Pharmacia & Upjohn Co; 2020.
Chatziralli I, Sergentanis T, Zagouri F, Chrysikos D, Ladas I, Zografos GC, et al. Ocular surface disease in breast cancer patients using aromatase inhibitors. Breast J. 2016;22(5):561–3. https://doi.org/10.1111/tbj.12633.
Inglis H, Boyle FM, Friedlander ML, Watson SL. Dry eyes and AIs: If you don’t ask you won’t find out. Breast. 2015;24(6):694–8. https://doi.org/10.1016/j.breast.2015.08.008.
Turaka K, Nottage JM, Hammersmith KM, Nagra PK, Rapuano CJ. Dry eye syndrome in aromatase inhibitor users. Clin Exp Ophthalmol. 2013;41(3):239–43. https://doi.org/10.1111/j.1442-9071.2012.02865.x.
Eisner A, Falardeau J, Toomey MD, Vetto JT. Retinal hemorrhages in anastrozole users. Optom Vis Sci. 2008;85(5):301–8. https://doi.org/10.1097/OPX.0b013e31816bea3b.
Karagöz B, Ayata A, Bilgi O, Uzun G, Unal M, Kandemir EG, et al. Hemicentral retinal artery occlusion in a breast cancer patient using anastrozole. Onkologie. 2009;32(7):421–3. https://doi.org/10.1159/000218369.
Bhatti MT, Salama AKS. Neuro-ophthalmic side effects of molecularly targeted cancer drugs. Eye (Lond). 2018;32(2):287–301. https://doi.org/10.1038/eye.2017.222.
Ho WL, Wong H, Yau T. The ophthalmological complications of targeted agents in cancer therapy: what do we need to know as ophthalmologists? Acta Ophthalmol. 2013;91(7):604–9. https://doi.org/10.1111/j.1755-3768.2012.02518.x.
Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. J Hematol Oncol. 2018;11(1):84. https://doi.org/10.1186/s13045-018-0624-2.
Breccia M, Gentilini F, Cannella L, Latagliata R, Carmosino I, Frustaci A, et al. Ocular side effects in chronic myeloid leukemia patients treated with imatinib. Leuk Res. 2008;32(7):1022–5. https://doi.org/10.1016/j.leukres.2007.10.016.
Schlemmer M, Bauer S, Schutte R, Hartmann JT, Bokemeyer C, Hosius C, et al. Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a German multicenter trial. Eur J Med Res. 2011;16(5):206–12. https://doi.org/10.1186/2047-783x-16-5-206.
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001;358(9291):1421–3. https://doi.org/10.1016/s0140-6736(01)06535-7.
Esmaeli B, Prieto VG, Butler CE, Kim SK, Ahmadi MA, Kantarjian HM, et al. Severe periorbital edema secondary to STI571 (Gleevec). Cancer. 2002;95(4):881–7. https://doi.org/10.1002/cncr.10729.
Fraunfelder FW, Solomon J, Druker BJ, Esmaeli B, Kuyl J. Ocular side-effects associated with imatinib mesylate (Gleevec). J Ocul Pharmacol Ther. 2003;19(4):371–5. https://doi.org/10.1089/108076803322279426.
McClelland CM, Harocopos GJ, Custer PL. Periorbital edema secondary to imatinib mesylate. Clin Ophthalmol. 2010;4:427–31. https://doi.org/10.2147/opth.s8521.
Qiu HB, Zhuang W, Wu T, Xin S, Lin CZ, Ruan HL, et al. Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1. Pharmacogenom J. 2018;18(3):460–6. https://doi.org/10.1038/tpj.2017.40.
Masood I, Negi A, Dua HS. Imatinib as a cause of cystoid macular edema following uneventful phacoemulsification surgery. J Cataract Refract Surg. 2005;31(12):2427–8. https://doi.org/10.1016/j.jcrs.2005.10.029.
Kusumi E, Arakawa A, Kami M, Kato D, Yuji K, Kishi Y, et al. Visual disturbance due to retinal edema as a complication of imatinib. Leukemia. 2004;18(6):1138–9. https://doi.org/10.1038/sj.leu.2403364.
Georgalas I, Pavesio C, Ezra E. Bilateral cystoid macular edema in a patient with chronic myeloid leukaemia under treatment with imanitib mesylate: report of an unusual side effect. Graefes Arch Clin Exp Ophthalmol. 2007;245(10):1585–6. https://doi.org/10.1007/s00417-007-0600-y.
Govind Babu K, Attili VS, Bapsy PP, Anupama G. Imatinib-induced optic neuritis in a patient of chronic myeloid leukemia. Int Ophthalmol. 2007;27(1):43–4. https://doi.org/10.1007/s10792-007-9038-9 (Epub 2007 Apr 5).
Rotstein DL, Sawicka K, Bharatha A, Montalban X, Lipton JH. CNS demyelination after initiating the tyrosine kinase inhibitor imatinib: A report of two cases. Mult Scler. 2020;26(9):1121–4. https://doi.org/10.1177/1352458519892914 (Epub 2019 Dec 17).
Rafei H, Jabbour EJ, Kantarjian H, Sinicrope KD, Kamiya-Matsuoka C, Mehta RS, et al. Neurotoxic events associated with BCR-ABL1 tyrosine kinase inhibitors: a case series. Leuk Lymphoma. 2019;60(13):3292–5. https://doi.org/10.1080/10428194.2019.1633635.
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–9. https://doi.org/10.1056/NEJMoa0912614.
Moore DC, Muslimani A, Sinclair P. Nilotinib-induced ocular toxicity: a case report. Am J Ther. 2018;25(5):e570–1. https://doi.org/10.1097/MJT.0000000000000650.
Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531–41. https://doi.org/10.1056/NEJMoa055229.
Monge KS, Galvez-Ruiz A, Alvarez-Carron A, Quijada C, Matheu A. Optic neuropathy secondary to dasatinib in the treatment of a chronic myeloid leukemia case. Saudi J Ophthalmol. 2015;29(3):227–31. https://doi.org/10.1016/j.sjopt.2014.12.004.
Sharma S, Garg N, Ghiuzeli CM. Unusual case of dasatinib-associated acute bilateral hyphemas leading to blindness in a patient with chronic myeloid leukaemia. BMJ Case Rep. 2018. https://doi.org/10.1136/bcr-2018-225705.
Leroy E, Constantinescu SN. Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition. Leukemia. 2017;31(12):2853. https://doi.org/10.1038/leu.2017.158.
Wathes R, Moule S, Milojkovic D. Progressive multifocal leukoencephalopathy associated with ruxolitinib. N Engl J Med. 2013;369(2):197–8. https://doi.org/10.1056/NEJMc1302135.
Reoma LB, Trindade CJ, Monaco MC, Solis J, Montojo MG, Vu P, et al. Fatal encephalopathy with wild-type JC virus and ruxolitinib therapy. Ann Neurol. 2019;86(6):878–84. https://doi.org/10.1002/ana.25608.
Ballesta B, Gonzalez H, Martin V, Ballesta JJ. Fatal ruxolitinib-related JC virus meningitis. J Neurovirol. 2017;23(5):783–5. https://doi.org/10.1007/s13365-017-0558-4.
Goldberg RA, Reichel E, Oshry LJ. Bilateral toxoplasmosis retinitis associated with ruxolitinib. N Engl J Med. 2013;369(7):681–3. https://doi.org/10.1056/NEJMc1302895.
von Hofsten J, Johnsson Forsberg M, Zetterberg M. Cytomegalovirus retinitis in a patient who received ruxolitinib. N Engl J Med. 2016;374(3):296–7. https://doi.org/10.1056/NEJMc1413918.
Eyal O, Flaschner M, Ben Yehuda A, Rund D. Varicella-zoster virus meningoencephalitis in a patient treated with ruxolitinib. Am J Hematol. 2017;92(5):E74–5. https://doi.org/10.1002/ajh.24688.
Moruno-Rodriguez A, Sanchez-Vicente JL, Rueda-Rueda T, Lechon-Caballero B, Munoz-Morales A, Lopez-Herrero F. Invasive aspergillosis manifesting as retinal necrosis in a patient treated with ruxolitinib. Arch Soc Esp Oftalmol. 2019;94(5):237–41. https://doi.org/10.1016/j.oftal.2018.12.006.
FDA. Highlights of prescribing information.
Liu LY, King BA. Response to tofacitinib therapy of eyebrows and eyelashes in alopecia areata. J Am Acad Dermatol. 2019;80(6):1778–9. https://doi.org/10.1016/j.jaad.2018.11.037.
Winthrop KL, Melmed GY, Vermeire S, Long MD, Chan G, Pedersen RD, et al. Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflamm Bowel Dis. 2018;24(10):2258–65. https://doi.org/10.1093/ibd/izy131.
Cugley DR, Darby J, Lim LL. Tofacitinib-associated cytomegalovirus retinitis. Rheumatology (Oxford). 2020;59(9):e35–7. https://doi.org/10.1093/rheumatology/kez681.
Yanagisawa K, Ogawa Y, Hosogai M, Todokoro D, Mitsui T, Yokohama A, et al. Cytomegalovirus retinitis followed by immune recovery uveitis in an elderly patient with rheumatoid arthritis undergoing administration of methotrexate and tofacitinib combination therapy. J Infect Chemother. 2017;23(8):572–5. https://doi.org/10.1016/j.jiac.2017.03.002.
Kobak S. Tofacitinib-induced Ramsay-Hunt syndrome in a patient with rheumatoid arthritis. Curr Drug Saf. 2020. https://doi.org/10.2174/1574886315999200819153827.
Eli Lilly and Company. Olumiant (Baricitinib) [package insert]. U.S. Food and Drug Administration. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207924s000lbl.pdf. Accessed 1 Jan 2021.
Lee JY, Gallo RA, Vu DM, Anagnostopoulos AG, Rong AJ. Fedratinib-induced orbital inflammation. Orbit. 2020. https://doi.org/10.1080/01676830.2020.1852263.
Winthrop K, Nash P, Yamaoka K, Mysler E, Calabrese L, Khan N, et al. THU0218 incidence and risk factors for herpes zoster in rheumatoid arthritis patients receiving upadacitinib. Ann Rheum Dis. 2020;79(Suppl 1):335. https://doi.org/10.1136/annrheumdis-2020-eular.2744.
Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299–312. https://doi.org/10.1038/s41375-018-0357-9.
Wu M, Li C, Zhu X. FLT3 inhibitors in acute myeloid leukemia. J Hematol Oncol. 2018;11(1):133. https://doi.org/10.1186/s13045-018-0675-4.
Fraunfelder FT, Fraunfelder FW. Oral anti-vascular endothelial growth factor drugs and ocular adverse events. J Ocul Pharmacol Ther. 2018;34(6):432–5. https://doi.org/10.1089/jop.2018.0019.
Li ZY, Fan XX, Wang YJ, Yao K, Liu ZW, Pan WT, et al. Metastatic renal cell carcinoma: the first report of unilateral fundus hemorrhage induced by sorafenib. Oncotarget. 2016;7(23):35181–7. https://doi.org/10.18632/oncotarget.9285.
Szczepanik S, Kecik D. Bilateral central retinal vein occlusion in a patient with disseminated metastatic renal cell carcinoma treated with sorafenib. Retin Cases Brief Rep. 2012;6(2):148–50. https://doi.org/10.1097/ICB.0b013e3182160965.
Bhatia S, Moon J, Margolin KA, Weber JS, Lao CD, Othus M, et al. Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. PLoS ONE. 2012;7(11):e48787. https://doi.org/10.1371/journal.pone.0048787.
Kapiteijn E, Brand A, Kroep J, Gelderblom H. Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome. Ann Oncol. 2007;18(10):1745–7. https://doi.org/10.1093/annonc/mdm454.
Chen A, Agarwal N. Reversible posterior leucoencephalopathy syndrome associated with sunitinib. Intern Med J. 2009;39(5):341–2. https://doi.org/10.1111/j.1445-5994.2009.01908.x.
Padhy BM, Shanmugam SP, Gupta YK, Goyal A. Reversible posterior leucoencephalopathy syndrome in an elderly male on sunitinib therapy. Br J Clin Pharmacol. 2011;71(5):777–9. https://doi.org/10.1111/j.1365-2125.2010.03893.x.
Na S, Kim T. Optic neuritis associated with sunitinib. Neurol Sci. 2020. https://doi.org/10.1007/s10072-020-04713-x.
Yoong J, Chong G, Hamilton K. Bilateral papilledema on sunitinib therapy for advanced renal cell carcinoma. Med Oncol (Northwood, London, England). 2011;28(Suppl 1):S395–7. https://doi.org/10.1007/s12032-010-9719-5.
Wegner A, Khoramnia R. Neurosensory retinal detachment due to sunitinib treatment. Eye (Lond). 2011;25(11):1517–8. https://doi.org/10.1038/eye.2011.200 ((Epub 2011 Aug 19)).
Novartis Pharmaceuticals Corp. Rydapt (Midostaurin) [package insert]. U.S. Food and Drug Administration website. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997s000lbl.pdf. Accessed 1 Jan 2021.
Astellas Pharma US, Inc. Xospata (Gilteritinib) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211349s001lbl.pdf. Accessed 1 Jan 2021.
Bayer HealthCare Pharmaceuticals Inc. Stivarga (Regorafenib) [package insert]. U.S. Food and Drug Administration Website. 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204369lbl.pdf. Accessed 1 Jan 2021.
Joussen AM, Wolf S, Kaiser PK, Boyer D, Schmelter T, Sandbrink R, et al. The Developing regorafenib eye drops for neovascular age-related macular degeneration (DREAM) study: an open-label phase II trial. Br J Clin Pharmacol. 2019;85(2):347–55. https://doi.org/10.1111/bcp.13794 ((Epub 2018 Nov 25)).
Wen T, Wang J, Shi Y, Qian H, Liu P. Inhibitors targeting Bruton’s tyrosine kinase in cancers: drug development advances. Leukemia. 2020. https://doi.org/10.1038/s41375-020-01072-6.
Byrd JC, Brown JR, O’Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23. https://doi.org/10.1056/NEJMoa1400376.
Kunkler AL, Binkley EM, Mantopoulos D, Hendershot AJ, Ohr MP, Kendra KL, et al. Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics. Graefes Arch Clin Exp Ophthalmol. 2019;257(8):1771–81. https://doi.org/10.1007/s00417-019-04337-8.
Mosna K, Ladicka M, Drgona L, Vranovska M, Hojsikova I, Tomasova R, et al. Ibrutinib treatment of mantle cell lymphoma complicated by progressive multifocal leukoencephalopathy. Int J Clin Pharmacol Ther. 2020;58(6):343–50. https://doi.org/10.5414/CP203663.
Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, et al. Treatment of patients with relapsed or refractory mantle-cell lymphoma with zanubrutinib, a selective inhibitor of Bruton’s tyrosine kinase. Clin Cancer Res. 2020;26(16):4216–24. https://doi.org/10.1158/1078-0432.CCR-19-3703 (Epub 2020 May 27).
Ayati A, Moghimi S, Salarinejad S, Safavi M, Pouramiri B, Foroumadi A. A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy. Bioorg Chem. 2020;99:103811. https://doi.org/10.1016/j.bioorg.2020.103811.
Hager T, Seitz B. Ocular side effects of biological agents in oncology: what should the clinician be aware of? Onco Targets Ther. 2013;7:69–77. https://doi.org/10.2147/OTT.S54606.
Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003;21(12):2237–46. https://doi.org/10.1200/JCO.2003.10.038.
Tullo AB, Esmaeli B, Murray PI, Bristow E, Forsythe BJ, Faulkner K. Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (“Iressa”, ZD1839) in Phase I and II clinical trials. Eye (Lond). 2005;19(7):729–38. https://doi.org/10.1038/sj.eye.6701630.
Schütte W, Nagel S, Schaedlich S, Brust D, Blankenburg T. Clinical benefit in NSCLC: advanced-stage patients require symptom-improving palliation. Experiences from the “Iressa” expanded access program. Onkologie. 2005;28(4):195–8. https://doi.org/10.1159/000084204 (Epub 2005 Mar 31).
Ibrahim E, Dean WH, Price N, Gomaa A, Ayre G, Guglani S, et al. Perforating corneal ulceration in a patient with lung metastatic adenocarcinoma treated with gefitinib: a case report. Case Rep Ophthalmol Med. 2012;2012:379132. https://doi.org/10.1155/2012/379132 (Epub 2012 Dec 18).
Shin E, Lim DH, Han J, Nam D-H, Park K, Ahn M-J, et al. Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors. BMC Ophthalmol. 2020;20(1):19. https://doi.org/10.1186/s12886-019-1285-9.
Huang JJ, Ma SX, Hou X, Wang Z, Zeng YD, Qin T, et al. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer. Chin J Cancer. 2015;34(2):94–8. https://doi.org/10.5732/cjc.014.10151 (Epub 2014 Nov 21).
Choi HD, Chang MJ. Eye, hepatobiliary, and renal disorders of erlotinib in patients with non-small-cell lung cancer: a meta-analysis. PLoS ONE. 2020;15(7):e0234818. https://doi.org/10.1371/journal.pone.0234818.
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–32. https://doi.org/10.1056/NEJMoa050753.
Lee SM, Khan I, Upadhyay S, Lewanski C, Falk S, Skailes G, et al. First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2012;13(11):1161–70. https://doi.org/10.1016/S1470-2045(12)70412-6.
Papadopoulos R, Chasapi V, Bachariou A. Trichomegaly induced by erlotinib. Orbit. 2008;27(4):329–30. https://doi.org/10.1080/01676830802222936.
Borkar DS, Lacouture ME, Basti S. Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors and their intermediate-term follow-up: a five-year review. Support Care Cancer. 2013;21(4):1167–74. https://doi.org/10.1007/s00520-012-1645-y.
Lane K, Goldstein SM. Erlotinib-associated trichomegaly. Ophthalmic Plast Reconstr Surg. 2007;23(1):65–6. https://doi.org/10.1097/IOP.0b013e31802d9802.
Carser JE, Summers YJ. Trichomegaly of the eyelashes after treatment with erlotinib in non-small cell lung cancer. J Thorac Oncol. 2006;1(9):1040–1.
Desai RU, Rachakonda LP, Saffra NA. Trichomegaly secondary to erlotinib. Can J Ophthalmol. 2009;44(6):e65. https://doi.org/10.3129/i09-158.
Tamura M, Takai Y, Nakamura S, Ohira A. A case report of pseudo-exfoliation syndrome with prolonged corneal epithelial regeneration because of erlotinib-induced unilateral corneal ulcer and anterior uveitis. Acta Ophthalmol. 2020. https://doi.org/10.1111/aos.14454.
Sobol EK, Ahmad S, Ibrahim K, Alfaro C, Pakett J, Esquenazi K, et al. Rapidly progressive streptococcus dysgalactiae corneal ulceration associated with erlotinib use in stage IV lung cancer. Am J Ophthalmol Case Rep. 2020;18:100630. https://doi.org/10.1016/j.ajoc.2020.100630.
Guarnieri A, Alfonso-Bartolozzi B, Ciufo G, Moreno-Montanes J, Gil-Bazo I. Plasma rich in growth factors for the treatment of rapidly progressing refractory corneal melting due to erlotinib in nonsmall cell lung cancer. Medicine (Baltimore). 2017;96(22):e7000. https://doi.org/10.1097/MD.0000000000007000.
Saint-Jean A, Sainz de la Maza M, Morral M, Torras J, Quintana R, Molina JJ, et al. Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases. Ophthalmology. 2012;119(9):1798–802. https://doi.org/10.1016/j.ophtha.2012.03.002.
Yoshioka H, Hotta K, Kiura K, Takigawa N, Hayashi H, Harita S, et al. A phase II trial of erlotinib monotherapy in pretreated patients with advanced non-small cell lung cancer who do not possess active EGFR mutations: Okayama Lung Cancer Study Group trial 0705. J Thorac Oncol. 2010;5(1):99–104. https://doi.org/10.1097/JTO.0b013e3181c20063.
Zhou Z, Sambhav K, Chalam KV. Erlotinib-associated severe bilateral recalcitrant keratouveitis after corneal EDTA chelation. Am J Ophthalmol Case Rep. 2016;4:1–3. https://doi.org/10.1016/j.ajoc.2016.06.003.
Hollhumer R, Moloney G, Jacob K. Corneal edema with a systemic epidermal growth factor receptor inhibitor. Can J Ophthalmol. 2017;52(3):e96–7. https://doi.org/10.1016/j.jcjo.2016.11.018.
Asai N, Ohkuni Y, Yamaguchi E, Kaneko N. Successful treatment of non-small cell lung cancer with gefitinib after erlotinib-induced severe eyelid erosion: two case reports. J Cancer Res Ther. 2015;11(3):653. https://doi.org/10.4103/0973-1482.139392.
Kau HC, Tsai CC. Erlotinib-related keratopathy in a patient underwent laser in situ keratomileusis. Cutan Ocul Toxicol. 2016;35(3):257–9. https://doi.org/10.3109/15569527.2015.1072546 (Epub 2015 Aug 12).
Morishige N, Hatabe N, Morita Y, Yamada N, Kimura K, Sonoda KH. Spontaneous healing of corneal perforation after temporary discontinuation of erlotinib treatment. Case Rep Ophthalmol. 2014;5(1):6–10. https://doi.org/10.1159/000358082.
Li M, Xiang J, Zhang C. When EGFR inhibitor meets autoimmune disease: severe corneal complications in a patient with Sjogren syndrome after erlotinib treatment. Eur J Ophthalmol. 2020. https://doi.org/10.1177/1120672120958300.
Rao V, Schneider E, Proia AD, Fekrat S. Development of bilateral acquired toxoplasmic retinochoroiditis during erlotinib therapy. JAMA Ophthalmol. 2014;132(9):1150–2. https://doi.org/10.1001/jamaophthalmol.2014.1088.
Salman A, Cerman E, Seckin D, Kanitez M. Erlotinib induced ectropion following papulopustular rash. J Dermatol Case Rep. 2015;9(2):46–8. https://doi.org/10.3315/jdcr.2015.1203(eCollection 2015 Jun 30).
Boehringer Ingelheim Pharmaceuticals, Inc. Gilotrif (Afatinib) [package insert]. U.S. Food and Drug Administration Website. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201292s014lbl.pdf. Accessed 1 Jan 2021.
Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013;31(27):3335–41. https://doi.org/10.1200/JCO.2012.45.0981.
McKelvie J, McLintock C, Elalfy M. Bilateral ulcerative keratitis associated with afatinib treatment for non-small-cell lung carcinoma. Cornea. 2019;38(3):384–5. https://doi.org/10.1097/ICO.0000000000001808.
Seiwert TY, Fayette J, Cupissol D, Del Campo JM, Clement PM, Hitt R, et al. A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. Ann Oncol. 2014;25(9):1813–20. https://doi.org/10.1093/annonc/mdu216.
Todokoro D, Itakura H, Ibe T, Kishi S. Anterior uveitis caused by ocular side effects of afatinib: a case report. Case Rep Ophthalmol. 2016;7(1):74–8. https://doi.org/10.1159/000444047.
Ariad Pharmaceuticals Inc. Alunbrig (Brigatinib) [package insert]. U.S. Food and Drug Administration Website. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208772s008lbl.pdf. Accessed 1 Jan 2021.
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020;38(31):3592–603. https://doi.org/10.1200/JCO.20.00505.
Huber RM, Hansen KH, Paz-Ares Rodriguez L, West HL, Reckamp KL, Leighl NB, et al. Brigatinib in crizotinib-refractory ALK+ NSCLC: 2-year follow-up on systemic and intracranial outcomes in the phase 2 ALTA trial. J Thorac Oncol. 2020;15(3):404–15. https://doi.org/10.1016/j.jtho.2019.11.004.
Kawakami H, Sugioka K, Yonesaka K, Satoh T, Shimomura Y, Nakagawa K. Human epidermal growth factor eyedrops for cetuximab-related filamentary keratitis. J Clin Oncol. 2011;29(23):e678–9. https://doi.org/10.1200/JCO.2011.35.0694 (Epub 2011 Jun 20).
Kurosaki T, Mitani S, Tanaka K, Suzuki S, Kanemura H, Haratani K, et al. Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study. Anticancer Drugs. 2020. https://doi.org/10.1097/CAD.0000000000001006.
Foerster CG, Cursiefen C, Kruse FE. Persisting corneal erosion under cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody). Cornea. 2008;27(5):612–4. https://doi.org/10.1097/ICO.0b013e318166f483.
Aomatsu K, Sugioka K, Kodama-Takahashi A, Fukuda M, Mishima H, Kusaka S. Corneal perforation during combination chemotherapy including cetuximab in a patient with a history of herpetic keratitis. Case Rep Oncol Med. 2020;2020:6802408. https://doi.org/10.1155/2020/6802408.
Vano-Galvan S, Rios-Buceta L, Ma DL, Fernandez-Chacon C, Viera JC, Jaen P. Cetuximab-induced hypertrichosis of the scalp and eyelashes. J Am Acad Dermatol. 2010;62(3):531–3. https://doi.org/10.1016/j.jaad.2009.02.023.
Matos LV, Pissarra A, Malheiro M, Placido AN. Trichomegaly of the eyelashes induced by the epidermal growth factor receptor inhibitor cetuximab in the treatment of metastatic colorectal cancer. BMJ Case Rep. 2019. https://doi.org/10.1136/bcr-2018-228968.
Melichar B, Nemcova I. Eye complications of cetuximab therapy. Eur J Cancer Care (Engl). 2007;16(5):439–43. https://doi.org/10.1111/j.1365-2354.2006.00763.x.
Rodriguez NA, Ascaso FJ. Trichomegaly and poliosis of the eyelashes during cetuximab treatment of metastatic colorectal cancer. J Clin Oncol. 2011;29(18):e532–3. https://doi.org/10.1200/JCO.2011.34.6858 (Epub 2011 Apr 11).
Koksal UI, Pilanci KN, Ordu C, Okutur K, Saglam S, Demir G. Trichomegaly induced by cetuximab: case series and review the literature. Am J Ther. 2016;23(5):e1226–9. https://doi.org/10.1097/MJT.0000000000000189.
Bouche O, Brixi-Benmansour H, Bertin A, Perceau G, Lagarde S. Trichomegaly of the eyelashes following treatment with cetuximab. Ann Oncol. 2005;16(10):1711–2. https://doi.org/10.1093/annonc/mdi300 (Epub 2005 Jun 21).
Cohen PR, Escudier SM, Kurzrock R. Cetuximab-associated elongation of the eyelashes: case report and review of eyelash trichomegaly secondary to epidermal growth factor receptor inhibitors. Am J Clin Dermatol. 2011;12(1):63–7. https://doi.org/10.2165/11531920-000000000-00000.
Scofield-Kaplan S, Todaro J, Winn BJ. Reversible cicatricial ectropion associated with EGFR inhibitors. Orbit. 2018;37(5):364–7. https://doi.org/10.1080/01676830.2017.1423342.
AstraZeneca Pharmaceuticals LP. Tagrisso (Osimertinib) [package insert]. U.S. Food and Drug Administration Website. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf. Accessed 1 Jan 2021.
Shin E, Lim DH, Han J, Nam DH, Park K, Ahn MJ, et al. Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors. BMC Ophthalmol. 2020;20(1):19. https://doi.org/10.1186/s12886-019-1285-9.
Chia PL, John T. Vortex keratopathy presumed secondary to AZD9291. J Thorac Oncol. 2015;10(12):1807–8. https://doi.org/10.1097/JTO.0000000000000634.
Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454–66. https://doi.org/10.1016/S1470-2045(17)30608-3.
Amgen, Inc. Vectibix (Panitumumab) [package insert]. U.S. Food and Drug Administration Website. 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125147s080lbl.pdf. Accessed 1 Jan 2021.
Jin HD, Blessing NW. Cicatricial ectropion and madarosis associated with panitumumab treatment of metastatic colorectal cancer. Am J Ophthalmol Case Rep. 2020;19:100810. doi:https://doi.org/10.1016/j.ajoc.2020.100810(eCollection 2020 Sep).
Eli Lilly and Company. Portrazza (Necitumumab) [package insert]. U.S. Food and Drug Administration Website. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125547s000lbl.pdf. Accessed 1 Jan 2021.
Markham A. Erdafitinib: first global approval. Drugs. 2019;79(9):1017–21. https://doi.org/10.1007/s40265-019-01142-9.
Dai S, Zhou Z, Chen Z, Xu G, Chen Y. Fibroblast growth factor receptors (FGFRs): structures and small molecule inhibitors. Cells. 2019. https://doi.org/10.3390/cells8060614.
Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338–48. https://doi.org/10.1056/NEJMoa1817323.
Bahleda R, Italiano A, Hierro C, Mita A, Cervantes A, Chan N, et al. Multicenter phase I study of erdafitinib (JNJ-42756493), oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced or refractory solid tumors. Clin Cancer Res. 2019;25(16):4888–97. https://doi.org/10.1158/1078-0432.CCR-18-3334 (Epub 2019 May 14).
Bauters G, Paques M, Borderie V, Bouheraoua N. Reversible corneal stromal thinning, acute-onset white cataract and angle-closure glaucoma due to erdafitinib, a fibroblast growth factor receptor inhibitor: report of three cases. J Fr Ophtalmol. 2020. https://doi.org/10.1016/j.jfo.2020.03.018.
Awad MM, Shaw AT. ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014;12(7):429–39.
Ishii T, Iwasawa S, Kurimoto R, Maeda A, Takiguchi Y, Kaneda M. Crizotinib-induced abnormal signal processing in the retina. PLoS ONE. 2015;10(8):e0135521. https://doi.org/10.1371/journal.pone.0135521.
Pfizer Inc. Xalkori (Crizotinib) [package insert]. U.S. Food and Drug Administration Website. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202570s021lbl.pdf. Accessed 1 Jan 2021.
Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13(10):1011–9. https://doi.org/10.1016/S1470-2045(12)70344-3.
Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94. https://doi.org/10.1056/NEJMoa1214886.
Chelala E, Hoyek S, Arej N, Kattan J, Kourie HR, Baakliny J, et al. Ocular and orbital side effects of ALK inhibitors: a review article. Future Oncol. 2019;15(16):1939–45. https://doi.org/10.2217/fon-2018-0608.
Chun SG, Iyengar P, Gerber DE, Hogan RN, Timmerman RD. Optic neuropathy and blindness associated with crizotinib for non-small-cell lung cancer with EML4-ALK translocation. J Clin Oncol. 2015;33(5):e25–6. https://doi.org/10.1200/JCO.2013.49.1985 (Epub 2014 Mar 10).
Das J, Das N. Chronic conjunctival chemosis-a new ocular side effect of crizotinib. Ophthalmic Plast Reconstr Surg. 2020. https://doi.org/10.1097/IOP.0000000000001710.
Solomon BJ, Kim EE, Winter M, Monti K, Tang Y, Wilner KD, et al. Ophthalmological assessment of crizotinib in advanced non-small-cell lung cancer. Lung Cancer. 2020;145:167–72. https://doi.org/10.1016/j.lungcan.2020.04.010 (Epub 2020 Apr 28).
Raedler LA. Zykadia (Ceritinib) approved for patients with crizotinib-resistant ALK-positive non-small-cell lung cancer. am health drug benefits. 2015;8(Spec Feature):163–6.
Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–38. https://doi.org/10.1056/NEJMoa1704795.
Genentech USA, Inc. Alecensa (Alectinib) [package insert]. U.S. Food and Drug Administration Website. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202570s021lbl.pdf. Accessed 1 Jan 2021.
Pfizer, Inc. Lorbrena (Lorlatinib) [package insert]. U.S. Food and Drug Administration Website. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210868s000lbl.pdf. Accessed 1 Jan 2021.
Genentech USA, Inc. Rozlytrek (Entrectinib) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212725s000lbl.pdf. Accessed 1 Jan 2021.
Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Devel Ther. 2016;10:2443–59. https://doi.org/10.2147/DDDT.S89114.
Heinrich MC, Jones RL, von Mehren M, Schoffski P, Serrano C, Kang YK, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020;21(7):935–46. https://doi.org/10.1016/S1470-2045(20)30269-2.
Cocorocchio E, Pala L, Conforti F, Guerini-Rocco E, De Pas T, Ferrucci PF. Successful treatment with avapritinib in patient with mucosal metastatic melanoma. Ther Adv Med Oncol. 2020;12:1758835920946158. https://doi.org/10.1177/1758835920946158.
Costa RLB, Czerniecki BJ. Clinical development of immunotherapies for HER2(+) breast cancer: a review of HER2-directed monoclonal antibodies and beyond. NPJ Breast Cancer. 2020;6:10. https://doi.org/10.1038/s41523-020-0153-3.
Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28(12):2024–31. https://doi.org/10.1200/JCO.2009.23.8451 (Epub 2010 Mar 22).
Saleh M, Bourcier T, Noel G, Speeg-Schatz C, Gaucher D. Bilateral macular ischemia and severe visual loss following trastuzumab therapy. Acta Oncol. 2011;50(3):477–8. https://doi.org/10.3109/0284186X.2011.555781 (Epub 2011 Feb 8).
Sridhar MS, Laibson PR, Rapuano CJ, Cohen EJ. Infectious crystalline keratopathy in an immunosuppressed patient. CLAO J. 2001;27(2):108–10.
Orlandi A, Fasciani R, Cassano A, Agresta A, Calegari MA, Caporossi A, et al. Trastuzumab-induced corneal ulceration: successful no-drug treatment of a “blind” side effect in a case report. BMC Cancer. 2015;15:973. https://doi.org/10.1186/s12885-015-1969-3.
Huillard O, Bakalian S, Levy C, Desjardins L, Lumbroso-Le Rouic L, Pop S, et al. Ocular adverse events of molecularly targeted agents approved in solid tumours: a systematic review. Eur J Cancer. 2014;50(3):638–48. https://doi.org/10.1016/j.ejca.2013.10.016.
Genentech USA, Inc. Perjeta (Pertuzumab) [package insert]. U.S. Food and Drug Administration Website. 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125409s051lbl.pdf. Accessed 1 Jan 2021.
Qin S, Li A, Yi M, Yu S, Zhang M, Wu K. Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy. J Hematol Oncol. 2019;12(1):27. https://doi.org/10.1186/s13045-019-0718-5.
Singh R, Wurzelmann JI, Ye L, Henderson L, Hossain M, Trivedi T, et al. Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration. Retina. 2014;34(9):1787–95. https://doi.org/10.1097/IAE.0000000000000179.
Lifton J, Chow A, Moshfeghi AA. Failed laser retinopexy in a patient undergoing pazopanib therapy. RETINAL Cases Brief Rep. 2019. https://doi.org/10.1097/icb.0000000000000877.
Csaky KG, Dugel PU, Pierce AJ, Fries MA, Kelly DS, Danis RP, et al. Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration. Ophthalmology. 2015;122(3):579–88. https://doi.org/10.1016/j.ophtha.2014.09.036.
AstraZeneca Pharmaceuticals LP. Caprelsa (Vandetanib) [package insert]. U.S. Food and Drug Administration Website. 2011. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022405s007lbl.pdf. Accessed 1 Jan 2021.
Ahn J, Wee WR, Lee JH, Hyon JY. Vortex keratopathy in a patient receiving vandetanib for non-small cell lung cancer. Korean J Ophthalmol. 2011;25(5):355–7. https://doi.org/10.3341/kjo.2011.25.5.355.
Yeh S, Fine HA, Smith JA. Corneal verticillata after dual anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor 2 therapy (vandetanib) for anaplastic astrocytoma. Cornea. 2009;28(6):699–702. https://doi.org/10.1097/ICO.0b013e3181922146.
Kimura M, Kusuhara S, Tagami M, Nakamura M. Impaired retinal circulation during axitinib treatment for metastatic renal cell carcinoma. Case Rep Ophthalmol. 2019;10(1):5–10. https://doi.org/10.1159/000496197.
Jenkins TL, Aderman CM, Ho AC. Reversible retinal toxicity in a patient taking axitinib. Retin Cases Brief Rep. 9000;Publish Ah.
Sherman JH, Aregawi DG, Lai A, Fathallah-Shaykh HM, Bierman PJ, Linsky K, et al. Optic neuropathy in patients with glioblastoma receiving bevacizumab. Neurology. 2009;73(22):1924–6. https://doi.org/10.1212/WNL.0b013e3181c3fd00.
Seet RC, Rabinstein AA. Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. QJM. 2012;105(1):69–75. https://doi.org/10.1093/qjmed/hcr139.
Eli Lilly and Company. Cyramza (Ramucirumab) [package insert]. U.S. Food and Drug Administration Website. 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477s002lbl.pdf. Accessed 1 Jan 2021.
Exelixis, Inc. Cabometyx (Cabozantinib) [package insert]. U.S. Food and Drug Administration Website. 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208692s003lbl.pdf. Accessed 1 Jan 2021.
Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F. State-of-the-art strategies for targeting RET-dependent cancers. J Clin Oncol. 2020;38(11):1209–21. https://doi.org/10.1200/JCO.19.02551.
Blueprint Medicines Corporation. Gavreto (Pralsetinib) [package insert]. U.S. Food and Drug Administration Website. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213721s000lbl.pdf. Accessed 1 Jan 2021.
Eli Lilly and Company. Retevmo (Selpercatinib) [package insert]. U.S. Food and Drug Administration Website. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213246s000lbl.pdf. Accessed 1 Jan 2021.
Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer. 2019;18(1):26. https://doi.org/10.1186/s12943-019-0954-x.
Gilead Sciences, Inc. Zydelig (Idelalisib) [package insert]. U.S. Food and Drug Administration Website. 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf. Accessed 1 Jan 2021.
Verastem, Inc. Copiktra (Duvelisib) [package insert]. U.S. Food and Drug Administration Website. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211155s000lbl.pdf. Accessed 1 Jan 2021.
Novartis Pharmaceuticals Corporation. Piqray (Alpelisib) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf. Accessed 1 Jan 2021.
Zou Z, Tao T, Li H, Zhu X. mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci. 2020;10:31. https://doi.org/10.1186/s13578-020-00396-1.
Touhami S, Arzouk N, Darugar A, Heron E, Clarençon F, Bodaghi B et al. Everolimus-induced posterior reversible encephalopathy syndrome and bilateral optic neuropathy after kidney transplantation. Lippincott Williams and Wilkins; 2014. p. e102-e4.
Pascual J, Marcén R, Ortuño J. Clinical experience with everolimus (Certican): optimizing dose and tolerability. Transplantation. 2005. https://doi.org/10.1097/01.TP.0000162433.34739.61.
Schear MJ, Rodgers R. A case of everolimus-induced eyelid edema. Ophthalmic Plast Reconstr Surg. 2018;34(1):e21–2. https://doi.org/10.1097/IOP.0000000000000974.
Ratta R, Guida A, Scotte F, Neuzillet Y, Teillet AB, Lebret T, et al. PARP inhibitors as a new therapeutic option in metastatic prostate cancer: a systematic review. Prostate Cancer Prostatic Dis. 2020;23(4):549–60. https://doi.org/10.1038/s41391-020-0233-3.
Clovis Oncology, Inc. Rubraca (rucaparib) [package insert]. U.S. Food and Drug Administration Website. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209115s004lbl.pdf. Accessed 1 Jan 2021.
Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015;14(2):130–46. https://doi.org/10.1038/nrd4504.
Pfizer Inc. Ibrance (Palbociclib) [package insert]. U.S. Food and Drug Administration Website. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207103s004lbl.pdf. Accessed 1 Jan 2021.
Novartis Pharmaceuticals Corporation. Kisqali (Ribociclib) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209092s004lbl.pdf. Accessed 1 Jan 2021.
Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017;14(7):417–33. https://doi.org/10.1038/nrclinonc.2016.206.
Sklar BA, Gervasio KA, Leng S, Ghosh A, Chari A, Wu AY. Management and outcomes of proteasome inhibitor associated chalazia and blepharitis: a case series. BMC Ophthalmol. 2019. https://doi.org/10.1186/s12886-019-1118-x.
Dennis M, Maoz A, Hughes D, Sanchorawala V, Sloan JM, Sarosiek S. Bortezomib ocular toxicities: outcomes with ketotifen. Wiley-Liss Inc.; 2019. p. E80–2.
Fraunfelder FW, Yang HK. Association between bortezomib therapy and eyelid chalazia. JAMA Ophthalmol. 2016;134(1):88–90. https://doi.org/10.1001/jamaophthalmol.2015.3963.
Veys MC, Delforge M, Mombaerts I. Treatment with doxycycline for severe bortezomib-associated blepharitis. Clin Lymphoma Myeloma Leuk. 2016;16(7):e109–12. https://doi.org/10.1016/j.clml.2016.04.013.
Chacko JG, Behbehani R, Hundley KN, Al-Fanek Y. Bortezomib-associated optic atrophy in two patients with multiple myeloma. J Neuroophthalmol. 2018;38(4):473–5. https://doi.org/10.1097/WNO.0000000000000657.
Seggewiss-Bernhardt R, Bargou RC, Goh YT, Stewart AK, Spencer A, Alegre A et al., editors. Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma 2015/07//: John Wiley and Sons Inc.
Amgen Medical. Kyprolis (Carfilzomib) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202714s025lbl.pdf. Accessed 1 Jan 2021.
Takeda Pharmaceuticals America, Inc. Ninlaro (ixazomib) [package insert]. U.S. Food and Drug Administration Website. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdf. Accessed 1 Jan 2021.
Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-drug conjugates: a comprehensive review. Mol Cancer Res. 2020;18(1):3–19. https://doi.org/10.1158/1541-7786.MCR-19-0582.
Daiichi Sankyo, Inc. Enhertu (Trastuzumab Deruxtecan) [package insert]. U.S. Food and Drug Administration Website. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761139s000lbl.pdf. Accessed 1 Jan 2021.
Farooq AV, Degli Esposti S, Popat R, Thulasi P, Lonial S, Nooka AK, et al. Corneal epithelial findings in patients with multiple myeloma treated with antibody-drug conjugate belantamab mafodotin in the pivotal, randomized, DREAMM-2 study. Ophthalmol Ther. 2020. https://doi.org/10.1007/s40123-020-00280-8.
Richardson PG, Lee HC, Abdallah AO, Cohen AD, Kapoor P, Voorhees PM, et al. Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study. Blood Cancer J. 2020. https://doi.org/10.1038/s41408-020-00369-0.
Popat R, Warcel D, O’Nions J, Cowley A, Smith S, Tucker WR, et al. Characterization of response and corneal events with extended follow-up after belantamab mafodotin (GSK2857916) monotherapy for patients with relapsed multiple myeloma: a case series from the first-time-in-human clinical trial. Haematologica. 2020;105(5):e261–3. https://doi.org/10.3324/haematol.2019.235937.
GlaxoSmithKline. Blenrep (belantamab mafodotin-blmf) [package insert]. U.S. Food and Drug Administration Website. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761158s000lbl.pdf. Accessed 1 Jan 2021.
Kreps EO, Derveaux T, Denys H. Corneal changes in trastuzumab emtansine treatment. Clin Breast Cancer. 2018;18(4):e427–9. https://doi.org/10.1016/j.clbc.2018.03.005.
Tsuda M, Takano Y, Shigeyasu C, Imoto S, Yamada M. Abnormal corneal lesions induced by trastuzumab emtansine: an antibody-drug conjugate for breast cancer. Cornea. 2016;35(10):1378–80. https://doi.org/10.1097/ICO.0000000000000868.
Deklerck E, Denys H, Kreps EO. Corneal features in trastuzumab emtansine treatment: not a rare occurrence. Breast Cancer Res Treat. 2019;175(2):525–30. https://doi.org/10.1007/s10549-019-05179-y.
Kim CY, Kim N, Choung HK, In KS. Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla(R), T-DM1) administration: a case report. BMC Cancer. 2019;19(1):774. https://doi.org/10.1186/s12885-019-5986-5.
Astellas Pharma US, Inc. PADCEV (enfortumab vedotin-ejfv) [package insert]. U.S. Food and Drug Administration Website. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761137s000lbl.pdf. Accessed 1 Jan 2021.
Francis JH, Habib LA, Abramson DH, Yannuzzi LA, Heinemann M, Gounder MM, et al. Clinical and morphologic characteristics of MEK inhibitor-associated retinopathy: differences from central serous chorioretinopathy. Ophthalmology. 2017;124(12):1788–98. https://doi.org/10.1016/j.ophtha.2017.05.038.
Giuffrè C, Miserocchi E, Modorati G, Carnevali A, Marchese A, Querques L, et al. Central serous chorioretinopathylike mimicking multifocal vitelliform macular dystrophy: an ocular side effect of mitogen/extracellular signal-regulated kinase inhibitors. Retin Cases Brief Rep. 2018;12(3):172–6. https://doi.org/10.1097/icb.0000000000000491.
Schoenberger SD, Kim SJ. Bilateral multifocal central serous-like chorioretinopathy due to MEK inhibition for metastatic cutaneous melanoma. Case Rep Ophthalmol Med. 2013;2013:673796. https://doi.org/10.1155/2013/673796.
Sheyman AT, Scarinci F, Fawzi AA, Gill MK. Long-term evaluation of MEK inhibitor retinal toxicity with multimodal imaging. Ophthalmic Surg Lasers Imaging Retina. 2016;47(1):76–7. https://doi.org/10.3928/23258160-20151214-12.
Siedlecki J, Mackert M, Wolf A, Berking C, Priglinger SG, Eibl-Lindner K. Bilateral visual field defects in a patient treated with the mek and braf inhibitors trametinib and dabrafenib for melanoma of unknown origin. Retin Cases Brief Rep. 2019;13(3):215–9. https://doi.org/10.1097/icb.0000000000000585.
Zaloum A, Falet JR, Elkrief A, Chalk C. Myasthenia gravis following dabrafenib and trametinib for metastatic melanoma. Neurology. 2020;94(7):322–3. https://doi.org/10.1212/wnl.0000000000008860.
Niro A, Strippoli S, Alessio G, Sborgia L, Recchimurzo N, Guida M. Ocular toxicity in metastatic melanoma patients treated with mitogen-activated protein kinase kinase inhibitors: a case series. Am J Ophthalmol. 2015;160(5):959-67.e1. https://doi.org/10.1016/j.ajo.2015.07.035.
Asfuroglu M, Asfuroğlu Y. A novel side effect of mitogen-activated protein kinase inhibitor cobimetinib: acute corneal decompensation. Indian J Ophthalmol. 2019;67(12):2073–5. https://doi.org/10.4103/ijo.IJO_2025_18.
Avery RA, Trimboli-Heidler C, Kilburn LB. Separation of outer retinal layers secondary to selumetinib. J aapos. 2016;20(3):268–71. https://doi.org/10.1016/j.jaapos.2016.01.012.
Fonollosa A, Mesquida M, Adan A. Uveitic macular oedema after treatment with vemurafenib. Acta Ophthalmol. 2015;93(8):e686–7. https://doi.org/10.1111/aos.12678.
Klein O, Ribas A, Chmielowski B, Walker G, Clements A, Long GV, et al. Facial palsy as a side effect of vemurafenib treatment in patients with metastatic melanoma. J Clin Oncol. 2013;31(12):e215–7. https://doi.org/10.1200/jco.2012.45.7028.
Shailesh FN, Singh M, Tiwari U, Hutchins LF. Vemurafenib-induced bilateral facial palsy. J Postgrad Med. 2014;60(2):187–8. https://doi.org/10.4103/0022-3859.132339.
Taylor SC, Hrisomalos F, Linette GP, Rao PK. A case of recurrent bilateral uveitis independently associated with dabrafenib and pembrolizumab therapy. Am J Ophthalmol Case Rep. 2016;2:23–5. https://doi.org/10.1016/j.ajoc.2016.04.004.
Gogas HJ, Flaherty KT, Dummer R, Ascierto PA, Arance A, Mandala M, et al. Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. Eur J Cancer. 2019;119:97–106. https://doi.org/10.1016/j.ejca.2019.07.016.
Tsui E, Gonzales JA. Retinal vasculitis associated with ipilimumab. Ocul Immunol Inflamm. 2020;28(6):868–70. https://doi.org/10.1080/09273948.2019.1610460.
Francis JH, Jaben K, Santomasso BD, Canestraro J, Abramson DH, Chapman PB, et al. Immune checkpoint inhibitor-associated optic neuritis. Ophthalmology. 2020;127(11):1585–9. https://doi.org/10.1016/j.ophtha.2020.05.003.
Hahn L, Pepple KL. Bilateral neuroretinitis and anterior uveitis following ipilimumab treatment for metastatic melanoma. J Ophthalmic Inflamm Infect. 2016;6(1):14. https://doi.org/10.1186/s12348-016-0082-3.
Wilson MA, Guld K, Galetta S, Walsh RD, Kharlip J, Tamhankar M, et al. Acute visual loss after ipilimumab treatment for metastatic melanoma. J Immunother Cancer. 2016;4:66. https://doi.org/10.1186/s40425-016-0170-9.
Sun MM, Seleme N, Chen JJ, Zekeridou A, Sechi E, Walsh RD, et al. Neuro-ophthalmic complications in patients treated with CTLA-4 and PD-1/PD-L1 checkpoint blockade. J Neuroophthalmol. 2020. https://doi.org/10.1097/wno.0000000000001148.
Modjtahedi BS, Maibach H, Park S. Multifocal bilateral choroidal neovascularization in a patient on ipilimumab for metastatic melanoma. Cutan Ocul Toxicol. 2013;32(4):341–3. https://doi.org/10.3109/15569527.2013.781618.
Crews J, Agarwal A, Jack L, Xu D, Do DV, Nguyen QD. Ipilimumab-associated retinopathy. Ophthalmic Surg Lasers Imaging Retina. 2015;46(6):658–60. https://doi.org/10.3928/23258160-20150610-10.
Mantopoulos D, Kendra KL, Letson AD, Cebulla CM. Bilateral choroidopathy and serous retinal detachments during ipilimumab treatment for cutaneous melanoma. JAMA Ophthalmol. 2015;133(8):965–7. https://doi.org/10.1001/jamaophthalmol.2015.1128.
Miyakubo T, Mukai R, Nakamura K, Matsumoto H, Akiyama H. A case of ipilimumab-induced unusual serous retinal detachment in bilateral eyes. Int Med Case Rep J. 2019;12:355–61. https://doi.org/10.2147/imcrj.S225173.
Maller B, Peguero E, Tanvetyanon T. Ipilimumab/nivolumab-related opsoclonus-myoclonus-ataxia syndrome variant in a patient with malignant pleural mesothelioma. J Immunother (Hagerstown, Md: 1997). 2018;41(9):411–2. https://doi.org/10.1097/cji.0000000000000228.
Hassanzadeh B, DeSanto J, Kattah JC. Ipilimumab-induced adenohypophysitis and orbital apex syndrome: importance of early diagnosis and management. Neuroophthalmology. 2018;42(3):176–81. https://doi.org/10.1080/01658107.2017.1368090.
Voskens CJ, Goldinger SM, Loquai C, Robert C, Kaehler KC, Berking C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS ONE. 2013;8(1):e53745. https://doi.org/10.1371/journal.pone.0053745.
Alnabulsi R, Hussain A, DeAngelis D. Complete ophthalmoplegia in Ipilmumab and Nivolumab combination treatment for metastatic melanoma. Orbit. 2018;37(5):381–4. https://doi.org/10.1080/01676830.2017.1423349.
Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315(15):1600–9. https://doi.org/10.1001/jama.2016.4059.
Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18. https://doi.org/10.1016/s1470-2045(15)00083-2.
Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–17. https://doi.org/10.1016/s0140-6736(14)60958-2.
Basilious A, Lloyd JC. Posterior subcapsular cataracts and hypotony secondary to severe pembrolizumab induced uveitis: case report. Can J Ophthalmol. 2016;51(1):e4-6. https://doi.org/10.1016/j.jcjo.2015.09.008.
Golash V, Almeida G. Pembrolizumab-related bilateral ocular hypotony, uveitis, cataracts, exudative retinal, and choroidal detachments: an unusual success story. J Immunother (Hagerstown, Md: 1997). 2020;43(9):283–5. https://doi.org/10.1097/cji.0000000000000328.
Thomas M, Armenti ST, Ayres MB, Demirci H. Uveal effusion after immune checkpoint inhibitor therapy. JAMA Ophthalmol. 2018;136(5):553–6. https://doi.org/10.1001/jamaophthalmol.2018.0920.
Shimada T, Hoshino Y, Tsunemi T, Hattori A, Nakagawa E, Yokoyama K, et al. Neuromyelitis optica spectrum disorder after treatment with pembrolizumab. Multiple Scler Relat Disord. 2020;37:101447. https://doi.org/10.1016/j.msard.2019.101447.
Roberts P, Fishman GA, Joshi K, Jampol LM. Chorioretinal lesions in a case of melanoma-associated retinopathy treated with pembrolizumab. JAMA Ophthalmol. 2016;134(10):1184–8. https://doi.org/10.1001/jamaophthalmol.2016.2944.
Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74(10):1216–22. https://doi.org/10.1001/jamaneurol.2017.1912.
Seki M, Uruha A, Ohnuki Y, Kamada S, Noda T, Onda A, et al. Inflammatory myopathy associated with PD-1 inhibitors. J Autoimmun. 2019;100:105–13. https://doi.org/10.1016/j.jaut.2019.03.005.
Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology. 2017;89(11):1127–34. https://doi.org/10.1212/wnl.0000000000004359.
Nakatani Y, Tanaka N, Enami T, Minami S, Okazaki T, Komuta K. Lambert-eaton myasthenic syndrome caused by nivolumab in a patient with squamous cell lung cancer. Case Rep Neurol. 2018;10(3):346–52. https://doi.org/10.1159/000494078.
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro Oncol. 2018;20(5):674–86. https://doi.org/10.1093/neuonc/nox208.
Mancone S, Lycan T, Ahmed T, Topaloglu U, Dothard A, Petty WJ, et al. Severe neurologic complications of immune checkpoint inhibitors: a single-center review. J Neurol. 2018;265(7):1636–42. https://doi.org/10.1007/s00415-018-8890-z.
Miyamoto R, Nakashizuka H, Tanaka K, Wakatsuki Y, Onoe H, Mori R, et al. Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report. BMC Ophthalmol. 2020;20(1):221. https://doi.org/10.1186/s12886-020-01495-w.
Reddy M, Chen JJ, Kalevar A, Terribilini R, Agarwal A. Immune retinopathy associated with nivolumab administration for metastatic non-small cell lung cancer. Retin Cases Brief Rep. 2020;14(2):120–6. https://doi.org/10.1097/icb.0000000000000675.
Garibaldi M, Calabrò F, Merlonghi G, Pugliese S, Ceccanti M, Cristiano L, et al. Immune checkpoint inhibitors (ICIs)-related ocular myositis. Neuromusc Disord. 2020;30(5):420–3. https://doi.org/10.1016/j.nmd.2020.02.013.
Khoo A, Zhuang Y, Boundy K, Frasca J. Immune checkpoint inhibitor-related myositis associated with atezolizumab therapy. Neurol Clin Pract. 2019;9(3):e25–6. https://doi.org/10.1212/cpj.0000000000000597.
Sengul Samanci N, Ozan T, Çelik E, Demirelli FH. Optic neuritis related to atezolizumab treatment in a patient with metastatic non-small-cell lung cancer. JCO Oncol Pract. 2020;16(2):96–8. https://doi.org/10.1200/jop.19.00438.
Becquart O, Lacotte J, Malissart P, Nadal J, Lesage C, Guillot B et al. Myasthenia gravis induced by immune checkpoint inhibitors. J Immunother (Hagerstown, Md: 1997). 2019;42(8):309–12. https://doi.org/10.1097/cji.0000000000000278.
Carrera W, Baartman BJ, Kosmorsky G. A case report of drug-induced myopathy involving extraocular muscles after combination therapy with tremelimumab and durvalumab for non-small cell lung cancer. Neuroophthalmology. 2017;41(3):140–3. https://doi.org/10.1080/01658107.2017.1291686.
Jeyakumar N, Etchegaray M, Henry J, Lelenwa L, Zhao B, Segura A, et al. The terrible triad of checkpoint inhibition: a case report of myasthenia gravis, myocarditis, and myositis induced by cemiplimab in a patient with metastatic cutaneous squamous cell carcinoma. Case Rep Immunol. 2020;2020:5126717. https://doi.org/10.1155/2020/5126717.
Ghosh A, Harish Bindiganavile S, Bhat N, Lee AG. A case of miller fisher syndrome due to the use of cemiplimab. J Neuroophthalmol. 2020. https://doi.org/10.1097/wno.0000000000001062.
Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep. 1978;62(3):315–20.
Zinchuk O, Watanabe M, Hayashi N, Fukushima A, Ueno H. A case of tamoxifen keratopathy. Arch Ophthalmol. 2006;124(7):1046–8. https://doi.org/10.1001/archopht.124.7.1046.
Chung SE, Kim SW, Chung HW, Kang SW. Estrogen antagonist and development of macular hole. Korean J Ophthalmol. 2010;24(5):306–9. https://doi.org/10.3341/kjo.2010.24.5.306.
Cronin BG, Lekich CK, Bourke RD. Tamoxifen therapy conveys increased risk of developing a macular hole. Int Ophthalmol. 2005;26(3):101–5. https://doi.org/10.1007/s10792-005-5424-3.
Torrell Belzach N, Vela Segarra JI, Crespí Vilimelis J, Alhayek M. Bilateral macular hole related to tamoxifen low-dose toxicity. Case Rep Ophthalmol. 2020;11(3):528–33. https://doi.org/10.1159/000508327.
Cho AR, Yoon YH, Kim JG, Kim YJ, Lee JY. Uveoretinal adverse effects presented during systemic anticancer chemotherapy: a 10-year single center experience. J Korean Med Sci. 2018;33(7):e55. https://doi.org/10.3346/jkms.2018.33.e55.
Pugesgaard T, Von Eyben FE. Bilateral optic neuritis evolved during tamoxifen treatment. Cancer. 1986;58(2):383–6. https://doi.org/10.1002/1097-0142(19860715)58:2%3c383::aid-cncr2820580232%3e3.0.co;2-i.
Ashford AR, Donev I, Tiwari RP, Garrett TJ. Reversible ocular toxicity related to tamoxifen therapy. Cancer. 1988;61(1):33–5. https://doi.org/10.1002/1097-0142(19880101)61:1%3c33::aid-cncr2820610107%3e3.0.co;2-i.
Colley SM, Elston JS. Tamoxifen optic neuropathy. Clin Exp Ophthalmol. 2004;32(1):105–6. https://doi.org/10.1046/j.1442-9071.2004.00769.x.
Coppes OJ, Lukas RV, Fleming GF, Nichols J, Tenney M, Bernard J. Bilateral optic disc swelling following anastrozole therapy. Neuroophthalmology. 2014;38(5):268–71. https://doi.org/10.3109/01658107.2014.924968.
Wieder MS, Harooni M, Rusu I. Association of crystalline retinopathy with anastrozole. JAMA Ophthalmol. 2019;137(5):581–2. https://doi.org/10.1001/jamaophthalmol.2019.0064.
Sathiamoorthi S, Ruddy KJ, Bakri SJ. Association of uveitis and macular edema with anastrozole therapy. JAMA Ophthalmol. 2018;136(7):837–9. https://doi.org/10.1001/jamaophthalmol.2018.1700.
Moschos MM, Chatziralli IP, Zagouri F, Zografos GC. Macular oedema due to letrozole: a first case report. Clin Exp Optom. 2012;95(6):646–50. https://doi.org/10.1111/j.1444-0938.2012.00771.x.
Laroche M, Borg S, Lassoued S, De Lafontan B, Roché H. Joint pain with aromatase inhibitors: abnormal frequency of Sjögren’s syndrome. J Rheumatol. 2007;34(11):2259–63.
Amireskandari A, Nguyen E, Hinkle D, Mauger T. Subepithelial corneal deposits associated with exemestane. Case Rep Ophthalmol Med. 2020;2020:5703164. https://doi.org/10.1155/2020/5703164.
Papathanassiou M, Nikita E, Theodossiadis P, Theodossiadis GP, Vergados I. Exemestane-induced corneal epithelial changes. Cutan Ocul Toxicol. 2010;29(3):209–11. https://doi.org/10.3109/15569521003775013.
Epstein RJ. Visual impairment in myopic patients with breast cancer receiving adjuvant therapy with aromatase inhibitors. Clin Breast Cancer. 2009;9(3):184–6. https://doi.org/10.3816/CBC.2009.n.030.
Esmaeli B, Diba R, Ahmadi MA, Saadati HG, Faustina MM, Shepler TR, et al. Periorbital oedema and epiphora as ocular side effects of imatinib mesylate (Gleevec). Eye (Lond). 2004;18(7):760–2. https://doi.org/10.1038/sj.eye.6701315.
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472–80. https://doi.org/10.1056/NEJMoa020461.
Valeyrie L, Bastuji-Garin S, Revuz J, Bachot N, Wechsler J, Berthaud P, et al. Adverse cutaneous reactions to imatinib (STI571) in Philadelphia chromosome-positive leukemias: a prospective study of 54 patients. J Am Acad Dermatol. 2003;48(2):201–6. https://doi.org/10.1067/mjd.2003.44.
Bouche O, Cesne AL, Rios M, Chaigneau L, Italiano A, Duffaud F, et al. EPIGIST: an observational real-life study on patients with metastatic gastrointestinal stromal tumors receiving imatinib. PLoS ONE. 2018;13(9):e0204117. https://doi.org/10.1371/journal.pone.0204117.
Kanda T, Nishida T, Wada N, Kobayashi O, Yamamoto M, Sawaki A, et al. Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients. Int J Clin Oncol. 2013;18(1):38–45. https://doi.org/10.1007/s10147-011-0339-7 (Epub 2011 Nov 23).
Nishida T, Shirao K, Sawaki A, Koseki M, Okamura T, Ohtsu A, et al. Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202). Int J Clin Oncol. 2008;13(3):244–51. https://doi.org/10.1007/s10147-007-0746-y (Epub 2008 Jun 14).
Llamas-Velasco M, Ovejero-Merino E, Garcia-Diez A, Requena L, Dauden E, Steegmann JL. Cutaneous side effects in a cohort of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: General description and further characterization, correlation with photoexposition and study of hypopigmentation as treatment's prognostic factor. Dermatol Ther. 2020. https://doi.org/10.1111/dth.14428.
Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–27. https://doi.org/10.1056/NEJMoa1609324.
Radaelli F, Vener C, Ripamonti F, Iurlo A, Colombi M, Artoni A, et al. Conjunctival hemorrhagic events associated with imatinib mesylate. Int J Hematol. 2007;86(5):390–3. https://doi.org/10.1532/IJH97.E0741.
Gulati AP, Saif MW. Retinal neovascularization and hemorrhage associated with the use of imatinib (Gleevec((R))) in a patient being treated for gastrointestinal stromal tumor (GIST). Anticancer Res. 2012;32(4):1375–7.
Kwon SI, Lee DH, Kim YJ. Optic disc edema as a possible complication of Imatinib mesylate (Gleevec). Jpn J Ophthalmol. 2008;52(4):331–3. https://doi.org/10.1007/s10384-008-0561-7.
DeLuca C, Shenouda-Awad N, Haskes C, Wrzesinski S. Imatinib mesylate (Gleevec) induced unilateral optic disc edema. Optom Vis Sci. 2012;89(10):e16-22. https://doi.org/10.1097/OPX.0b013e318269111d.
Napolitano M, Santoro M, Mancuso S, Carlisi M, Raso S, Tarantino G et al. Late onset of unilateral optic disk edema secondary to treatment with imatinib mesylate. Clin Case Rep. 2017;5(10):1573–5. https://doi.org/10.1002/ccr3.1137(eCollection 2017 Oct).
Anzalone CL, Cohen PR, Kurzrock R, Cortes JE. Imatinib-induced postoperative periorbital purpura: GASP (Gleevec-Associated Surgical Purpura) in a woman with imatinib-treated chronic myelogenous leukemia. Dermatol Online J. 2014;20(1):21242.
Roth DB, Akbari S, Rothstein A. Macular ischemia associated with imatinib mesylate therapy for chronic myeloid leukemia. Retin Cases Brief Rep. 2009;3(2):161–4. https://doi.org/10.1097/ICB.0b013e318177f9d7.
Maurizot A, Beressi JP, Maneglier B, de la Marre NH, Spentchian M, Soury P, et al. Rapid clinical improvement of peripheral artery occlusive disease symptoms after nilotinib discontinuation despite persisting vascular occlusion. Blood Cancer J. 2014;4:e247. https://doi.org/10.1038/bcj.2014.66.
Sayin I, Ayli M, Oguz AK, Seval GC. Xanthelasma palpebrarum: a new side effect of nilotinib. BMJ Case Rep. 2016. https://doi.org/10.1136/bcr-2015-213511.
Cho JH, Kim KM, Kwon M, Kim JH, Lee J. Nilotinib in patients with metastatic melanoma harboring KIT gene aberration. Investig New Drugs. 2012;30(5):2008–14. https://doi.org/10.1007/s10637-011-9763-9 (Epub 2011 Nov 9).
Naithani R. Dasatinib-induced loss of eyebrows. Br J Haematol. 2017;179(3):362. https://doi.org/10.1111/bjh.14847(Epub 2017 Jul 24).
Song J, Song A, Palmares T, Song M, Song H. Ruxolitinib found to cause eyelash growth: a case report. J Med Case Rep. 2017;11(1):189. https://doi.org/10.1186/s13256-017-1304-5.
Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, et al. Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol. 2017;69(10):1960–8. https://doi.org/10.1002/art.40189.
Hussain SZ, Asghar A, Ikram M, Islam N. Development of skin hypopigmentation in a patient with metastatic papillary carcinoma thyroid treated with Sorafenib. BMC Endocr Disord. 2013;13:29. https://doi.org/10.1186/1472-6823-13-29.
Gaertner KM, Caldwell SH, Rahma O. A case of retinal tear associated with use of sorafenib. Front Oncol. 2014. https://doi.org/10.3389/fonc.2014.00196.
Mehraban Far P, Rullo J, Farmer J, Urton T. Recurrent uveitis related to ibrutinib for treatment of chronic lymphocytic leukemia. Ocul Immunol Inflamm. 2021. https://doi.org/10.1080/09273948.2020.1841802.
Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, et al. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019;134(11):851–9. https://doi.org/10.1182/blood.2019001160 (Epub 2019 Jul 24).
Pascual JC, Banuls J, Belinchon I, Blanes M, Massuti B. Trichomegaly following treatment with gefitinib (ZD1839). Br J Dermatol. 2004;151(5):1111–2. https://doi.org/10.1111/j.1365-2133.2004.06265.x.
Kirkpatrick CA, Almeida DR, Hornick AL, Chin EK, Boldt HC. Erlotinib-associated bilateral anterior uveitis: resolution with posterior sub-Tenon’s triamcinolone without erlotinib cessation. Can J Ophthalmol. 2015;50(5):e66–7. https://doi.org/10.1016/j.jcjo.2015.03.013.
Klein KA, Azzoli CG, Rifkin LM. Bilateral acute simultaneous onset anterior uveitis presumed secondary to erlotinib: a report of two cases. Am J Ophthalmol Case Rep. 2017;6:21–3. https://doi.org/10.1016/j.ajoc.2016.09.003.
Lim LT, Blum RA, Cheng CP, Hanifudin A. Bilateral anterior uveitis secondary to erlotinib. Eur J Clin Pharmacol. 2010;66(12):1277–8. https://doi.org/10.1007/s00228-010-0873-7.
Ali K, Kumar I, Usman-Saeed M, Usman SM. Erlotinib-related bilateral anterior uveitis. BMJ Case Rep. 2011. https://doi.org/10.1136/bcr.03.2011.3988.
Chan S, Ahern E, Chaudhry S, Hughes B. Bilateral acute anterior uveitis: a rare ocular side effect of erlotinib. BMJ Case Rep. 2019. https://doi.org/10.1136/bcr-2019-232868.
Vergou T, Stratigos AJ, Karapanagiotou EM, Matekovits AE, Dilana KD, Tsimboukis S, et al. Facial hypertrichosis and trichomegaly developing in patients treated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol. 2010;63(2):e56–8. https://doi.org/10.1016/j.jaad.2009.11.589.
Marquez G, Herrera-Acosta E, Vidal I, Galvany L, Iglesias M, Umbert P. A case of trichomegaly of the eyelashes and facial hypertrichosis induced by erlotinib (Tarceva). Int J Dermatol. 2009;48(1):97–8. https://doi.org/10.1111/j.1365-4632.2009.03752.x.
Medina Mendez CA, Ma PC, Singh AD. Acquired trichomegaly: trichomegaly secondary to erlotinib. JAMA Ophthalmol. 2014;132(9):1051. https://doi.org/10.1001/jamaophthalmol.2014.545.
Celik T, Kosker M. Ocular side effects and trichomegaly of eyelashes induced by erlotinib: a case report and review of the literature. Cont Lens Anterior Eye. 2015;38(1):59–60. https://doi.org/10.1016/j.clae.2014.08.005 (Epub 2014 Sep 22).
Fabbrocini G, Panariello L, Cacciapuoti S, Bianca D, Ayala F. Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors: report of 3 cases. Dermatitis. 2012;23(5):237–8. https://doi.org/10.1097/DER.0b013e31826e45d7.
Munoz J, Hanbali AS. Epidermal growth factor receptor-induced hirsutism and trichomegaly. Mayo Clin Proc. 2011;86(11):e50. https://doi.org/10.4065/mcp.2011.0356.
Zhang G, Basti S, Jampol LM. Acquired trichomegaly and symptomatic external ocular changes in patients receiving epidermal growth factor receptor inhibitors: case reports and a review of literature. Cornea. 2007;26(7):858–60. https://doi.org/10.1097/ICO.0b013e318064584a.
Methvin AB, Gausas RE. Newly recognized ocular side effects of erlotinib. Ophthalmic Plast Reconstr Surg. 2007;23(1):63–5. https://doi.org/10.1097/IOP.0b013e31802d97f0.
Sun P, Long J, Chen P, He Q, Gao X, Li S. Rapid onset of conjunctivitis associated with overdosing of erlotinib. J Clin Pharm Ther. 2018;43(2):296–8. https://doi.org/10.1111/jcpt.12641.
Johnson KS, Levin F, Chu DS. Persistent corneal epithelial defect associated with erlotinib treatment. Cornea. 2009;28(6):706–7. https://doi.org/10.1097/ICO.0b013e31818fdbc6.
Miguel-Gomez L, Vano-Galvan S, Garrido-Lopez P, Jaen-Olasolo P. Afatinib-induced hypertrichosis of the eyelashes and eyebrows. Indian J Dermatol Venereol Leprol. 2016;82(2):192–3. https://doi.org/10.4103/0378-6323.168914.
Joganathan V, Norris JH. Periocular manifestations of afatinib therapy. Ophthalmic Plast Reconstr Surg. 2019;35(1):e12–3. https://doi.org/10.1097/IOP.0000000000001277.
Manthri S, Chakraborty K. Blepharitis: a rare side effect related to cetuximab in patient with colorectal cancer. BMJ Case Rep. 2019. https://doi.org/10.1136/bcr-2019-231774.
Specenier P, Koppen C, Vermorken JB. Diffuse punctate keratitis in a patient treated with cetuximab as monotherapy. Ann Oncol. 2007;18(5):961–2. https://doi.org/10.1093/annonc/mdm116 (Epub 2007 Apr 17).
Deitch-Harel IM, Raskin EM, Habot-Wilner ZM, Friling RM, Amer RM, Kramer MM. Uveitis induced by biological agents used in cancer therapy. Ocul Immunol Inflamm. 2020. https://doi.org/10.1080/09273948.2020.1760310.
Goyal A, Blaes A. Trichomegaly associated with panitumumab. N Engl J Med. 2020;383(16):e94. https://doi.org/10.1056/NEJMicm2003622.
Fukata T, Ito Y, Miyagaki H, Nishida H, Toyoda Y, Shingai T, et al. A case of Stevens-Johnson syndrome induced by chemotherapy for metastatic colon cancer. Gan To Kagaku Ryoho. 2019;46(4):748–50.
Ramtohul P, Denis D, Comet A. Pseudovitelliform maculopathy associated with FGFR inhibitor therapy. Ophthalmol Retina. 2021;5(2):140. https://doi.org/10.1016/j.oret.2020.10.005.
Ou SI, Govindan R, Eaton KD, Otterson GA, Gutierrez ME, Mita AC, et al. Phase I results from a study of crizotinib in combination with erlotinib in patients with advanced nonsquamous non-small cell lung cancer. J Thorac Oncol. 2017;12(1):145–51. https://doi.org/10.1016/j.jtho.2016.09.131 (Epub 2016 Sep 30).
Vaccaro M, Riso G, Altavilla D, Cannavò SP. Eyelashes depigmentation following treatment with pazopanib for metastatic renal cell carcinoma. Blackwell Publishing Inc.; 2019.
Bausell RB, Soleimani A, Vinnett A, Baroni MD, Staub SA, Binion K et al. Corneal changes after belantamab mafodotin in multiple myeloma patients. Eye Contact Lens. 9000;Pre-Publication.
Rousseau A, Michot JM, Labetoulle M. Belantamab mafotodin-induced epithelial keratopathy masquerading myopic surgery. Ophthalmology. 2020;127(12):1626. https://doi.org/10.1016/j.ophtha.2020.07.047.
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BHF: investigation, methodology, data curation, writing—original draft, and visualization. PDT: investigation, methodology, data curation, and writing—original draft, and visualization. LAD: conceptualization, writing—review and editing, and supervision.
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Fortes, B.H., Tailor, P.D. & Dalvin, L.A. Ocular Toxicity of Targeted Anticancer Agents. Drugs 81, 771–823 (2021). https://doi.org/10.1007/s40265-021-01507-z
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DOI: https://doi.org/10.1007/s40265-021-01507-z