Brentuximab vedotin related bilateral Purtscher-like retinopathy unresponsive to pulse steroid therapy and intravitreal aflibercept injection

oc000080 10.3205/oc000080 urn:nbn:de:0183-oc0000800 Case Report Brentuximab vedotin related bilateral Purtscher-like retinopathy unresponsive to pulse steroid therapy and intravitreal aflibercept injection Ayhan Ayhan Ziya Z

Department of Ophthalmology, Dokuz Eylul University School of Medicine, Izmir, Turkey

author Kaya Kaya Sureyya Yigit SY

Department of Haematology-Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey

author Ozcan Ozcan Mehmet Ali MA

Department of Haematology-Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey

author Saatci Saatci Ali Osman AO

Department of Ophthalmology, Dokuz Eylul University School of Medicine, Mustafa Kemal Sahil Bul. No. 73, A Blok Daire 9, Narlidere, Izmir 35320, TurkeyDepartment of Ophthalmology, Dokuz Eylul University School of Medicine, Izmir, Turkey

osman.saatci@yahoo.com author German Medical Science GMS Publishing House

Düsseldorf

610 Brentixumab vedotin Hodgkin’s lymphoma Purtscher-like retinopathy 20171215 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). 2193-1496 7 GMS Ophthalmology Cases GMS Ophthalmol Cases 29 We describe a 36-year-old woman with a relapsing Hodgkin’s lymphoma who developed a severe bilateral sudden visual loss almost three weeks after the initiation of brentuximab therapy. Ancillary fundus tests yielded bilateral severe retinal arteriolar occlusion 360° and serous macular retinal detachment. No visual improvement could be achieved despite the pulse corticosteroid therapy and a single bilateral intravitreal aflibercept administration cessation of the brentuximab therapy. Unfortunately, she succumbed to respiratory failure almost six weeks after the diagnosis of Purtscher-like retinopathy. IntroductionPurtscher-like retinopathy is an occlusive microvasculopathy most often developed after cranial trauma, thoracic compression, acute pancreatitis, renal failure, various autoimmune disease and during the administration of a multitude of chemotherapeutic agents , , . Brentuximab vedotin is a targeted antibody-drug conjugate active against CD-30 positive cancer cells such as those associated with classical Hodgkin’s lymphoma and it becomes an important option for the management of patients who have failed high dose chemotherapy/autol</PlainText></TextGroup>og<TextGroup><PlainText>ous</PlainText></TextGroup> hematopoietic stem cell transplantation (AHSCT) or at least two prior chemotherapy regimens and as post-AHSCT consolidation therapy in patients who are at increased risk of relapse or progression after AHSCT <TextLink reference="4"></TextLink>, <TextLink reference="5"></TextLink>. We describe a patient with refractory Hodgkin’s lymphoma who developed Purtscher-like retinopathy after administration of brentuximab vedotin following HSCT. </Pgraph></TextBlock> <TextBlock linked="yes" name="Case description"> <MainHeadline>Case description</MainHeadline><Pgraph>A 36-year-old woman was referred to us by her haematologist for a sudden, severe, bilateral visual loss of two days’ duration. She was diagnosed to have stage 2B nodular sclerosing classic Hodgkin’s lymphoma almost a year ago and first underwent six cycles of adriablastin, bleomycin, vinblastine, dacarbazine (ABVD regimen) and then AHSCT due to progression of the disease process. However, early relapse was detected by comparing the baseline and control scans of positron emission tomography/computed tomography (PET/CT) after the AHSCT. Therefore, brentuximab vedotin (1.8 mg/kg once every 3 weeks) was administered for the consolidation therapy. However, she experienced bilateral, sudden, severe visual loss almost three weeks after the initiation of brentuximab therapy. </Pgraph><Pgraph>On our examination, her vision was counting fingers from 1 meter in OD and 2 meters in OS. Slit-lamp examination was unremarkable OU. Intraocular pressure was within normal limits bilaterally. Dilated fundus exam disclosed preretinal hemorrhages, scattered cotton-wool spots <TextGroup><PlainText>and w</PlainText></TextGroup>idespread yellowish discoloring of the retina (Figur<TextGroup><PlainText>e 1a,b </PlainText></TextGroup><ImgLink imgNo="1" imgType="figure"/>). Fluorescein angiogram showed extensive arteriolar closure 360° OU (Figure 1c,d <ImgLink imgNo="1" imgType="figure"/>). Optical coherence tomography exhibited severe serous macular retinal detachment in both eyes (Figure 1e,f <ImgLink imgNo="1" imgType="figure"/>). Recent blood investigations revealed a mild leukocytosis (total white cell count 14.6 10<Superscript>3</Superscript>/µl with an 80% neutrophilia) [normal, 4–10.3 10<Superscript>3</Superscript>/µl]) and mild anemia (hemoglobin: 9.0 g/dL [normal, 12–16 g/dL]). C-reactive protein was <TextGroup><PlainText>52.2 mg/ml</PlainText></TextGroup>. Serum urea and creatinine levels were 17.4 and 0.38 mg/dL, respectively (normal limits of serum urea and creatinine were 6–20 and 0.51–0.95 mg/dL, respectively). Peripheral blood smear examination showed normochromic normocytic erythrocytes, anisocytosis and neutrophilia. Platelet count was normal. </Pgraph><Pgraph>After evaluating the overall clinical situation, brentuximab therapy was discontinued and a diagnosis of Purtscher-like retinopathy in association with brentuximab treatment was assumed. She was hospitalized and received 1 gram of IV methylprednisolone for 3 days. As the visual acuity deteriorated despite the pulse therapy (Figure 2 <ImgLink imgNo="2" imgType="figure"/>), bilateral simultaneous intravitreal 2 mg aflibecept injection was given after reviewing the therapeutic options with the patient and the family. In order to combat with the systemic disease progression, cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone (CHOEP) regimen was commenced. One month after the diagnosis of bilateral Purtscher-like retinopathy, her vision was no light perception OU. Her general condition deteriorated and she was transferred to the intensive care unit. She unfortunately passed away almost six weeks after our diagnosis due to respiratory failure.</Pgraph></TextBlock> <TextBlock linked="yes" name="Discussion"> <MainHeadline>Discussion</MainHeadline><Pgraph>CD-30 is highly expressed on Reed-Sternberg cells that are the key finding of the Hodgkin’s disease and Brentuximab vedotin causes apoptosis of the CD-30 expressing tumor cells by preventing cell cycle progression of the G<Subscript>2</Subscript> to M phase through the distruption of cytosolic microtuble network. Brentuximab vedotin has some known side effects including peripheral sensory neuropathy and neutropenia that most often can be managed with only dose reduction <TextLink reference="4"></TextLink>, <TextLink reference="5"></TextLink>. No ocular complication was previously reported. </Pgraph><Pgraph>Many antineoplastic agents can produce various vessel changes ranging from simple phlebitis to even lethal widespread microangiopathy <TextLink reference="3"></TextLink>. Purtscher-like retinopathy is most often reported by administration of gemcit<TextGroup><PlainText>ab</PlainText></TextGroup>ine <TextLink reference="6"></TextLink>, <TextLink reference="7"></TextLink>. Sheyman et al. <TextLink reference="6"></TextLink> described a 64-year-old woman who was on chemotherapy regimen including the gemcitabine for the treatment of metastatic cholangiocarcinoma and she developed Purtscher-like retinopathy and nephropathy. Kovach et al. <TextLink reference="7"></TextLink> reported a 18-year-old woman who completed 5 cycles of combination treatment with gemcitabine and docataxel for the treatment of leiomyosarcoma and the clinical picture improved after the cessation of only gemcitabine. As the mechanism of Purtscher-like retinopathy, the direct endothelial damage was suggested <TextLink reference="8"></TextLink>.</Pgraph></TextBlock> <TextBlock linked="yes" name="Conclusion"> <MainHeadline>Conclusion</MainHeadline><Pgraph>We believe that brentuximab treatment might be linked to occurence of bilateral Purtscher-like retinopathy in the present case with Hodgkin’s lymphoma relapse and thereby we share our experience with the communities of ophthalmology and haematology. </Pgraph></TextBlock> <TextBlock linked="yes" name="Notes"> <MainHeadline>Notes</MainHeadline><SubHeadline>Competing interests</SubHeadline><Pgraph>The authors declare that they have no competing interests.</Pgraph></TextBlock> <References linked="yes"> <Reference refNo="1"> <RefAuthor>Agrawal A</RefAuthor> <RefAuthor>McKibbin M</RefAuthor> <RefTitle>Purtscher’s retinopathy: epidemiology, clinical features and outcome</RefTitle> <RefYear>2007</RefYear> <RefJournal>Br J Ophthalmol</RefJournal> <RefPage>1456-9</RefPage> <RefTotal>Agrawal A, McKibbin M. Purtscher’s retinopathy: epidemiology, clinical features and outcome. Br J Ophthalmol. 2007 Nov;91(11):1456-9. DOI: 10.1136/bjo.2007.117408</RefTotal> <RefLink>http://dx.doi.org/10.1136/bjo.2007.117408</RefLink> </Reference> <Reference refNo="2"> <RefAuthor>Miguel AI</RefAuthor> <RefAuthor>Henriques F</RefAuthor> <RefAuthor>Azevedo LF</RefAuthor> <RefAuthor>Loureiro AJ</RefAuthor> <RefAuthor>Maberley DA</RefAuthor> <RefTitle>Systematic review of Purtscher’s and Purtscher-like retinopathies</RefTitle> <RefYear>2013</RefYear> <RefJournal>Eye (Lond)</RefJournal> <RefPage>1-13</RefPage> <RefTotal>Miguel AI, Henriques F, Azevedo LF, Loureiro AJ, Maberley DA. Systematic review of Purtscher’s and Purtscher-like retinopathies. Eye (Lond). 2013 Jan;27(1):1-13. DOI: 10.1038/eye.2012.222</RefTotal> <RefLink>http://dx.doi.org/10.1038/eye.2012.222</RefLink> </Reference> <Reference refNo="3"> <RefAuthor>Shahab N</RefAuthor> <RefAuthor>Haider S</RefAuthor> <RefAuthor>Doll DC</RefAuthor> <RefTitle>Vascular toxicity of antineoplastic agents</RefTitle> <RefYear>2006</RefYear> <RefJournal>Semin Oncol</RefJournal> <RefPage>121-38</RefPage> <RefTotal>Shahab N, Haider S, Doll DC. Vascular toxicity of antineoplastic agents. Semin Oncol. 2006 Feb;33(1):121-38. DOI: 10.1053/j.seminoncol.2005.11.006</RefTotal> <RefLink>http://dx.doi.org/10.1053/j.seminoncol.2005.11.006</RefLink> </Reference> <Reference refNo="4"> <RefAuthor>Scott LJ</RefAuthor> <RefTitle>Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma</RefTitle> <RefYear>2017</RefYear> <RefJournal>Drugs</RefJournal> <RefPage>435-445</RefPage> <RefTotal>Scott LJ. Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Drugs. 2017 Mar;77(4):435-445. DOI: 10.1007/s40265-017-0705-5</RefTotal> <RefLink>http://dx.doi.org/10.1007/s40265-017-0705-5</RefLink> </Reference> <Reference refNo="5"> <RefAuthor>Anonym</RefAuthor> <RefTitle>Brentuximab vedotin (sgn35) drug description</RefTitle> <RefYear></RefYear> <RefJournal>ADC Review</RefJournal> <RefPage></RefPage> <RefTotal>Brentuximab vedotin (sgn35) drug description. ADC Review. Available from: https://adcreview.com/brentuximab-vedotin-sgn35/</RefTotal> <RefLink>https://adcreview.com/brentuximab-vedotin-sgn35/</RefLink> </Reference> <Reference refNo="6"> <RefAuthor>Sheyman AT</RefAuthor> <RefAuthor>Wald KJ</RefAuthor> <RefAuthor>Pahk PJ</RefAuthor> <RefAuthor>Freund KB</RefAuthor> <RefTitle>Gemcitabine associated retinopathy and nephropathy</RefTitle> <RefYear>2014</RefYear> <RefJournal>Retin Cases Brief Rep</RefJournal> <RefPage>107-9</RefPage> <RefTotal>Sheyman AT, Wald KJ, Pahk PJ, Freund KB. Gemcitabine associated retinopathy and nephropathy. Retin Cases Brief Rep. 2014;8(2):107-9. DOI: 10.1097/ICB.0000000000000015</RefTotal> <RefLink>http://dx.doi.org/10.1097/ICB.0000000000000015</RefLink> </Reference> <Reference refNo="7"> <RefAuthor>Kovach JL</RefAuthor> <RefTitle>Gemcitabine-induced retinopathy</RefTitle> <RefYear>2016</RefYear> <RefJournal>Retin Cases Brief Rep</RefJournal> <RefPage></RefPage> <RefTotal>Kovach JL. Gemcitabine-induced retinopathy. Retin Cases Brief Rep. 2016 Oct 31. DOI: 10.1097/ICB.0000000000000471</RefTotal> <RefLink>http://dx.doi.org/10.1097/ICB.0000000000000471</RefLink> </Reference> <Reference refNo="8"> <RefAuthor>Tran TH</RefAuthor> <RefAuthor>Desauw C</RefAuthor> <RefAuthor>Rose C</RefAuthor> <RefTitle>Gemcitabine-induced retinopathy in a diabetic patient</RefTitle> <RefYear>2009</RefYear> <RefJournal>Acta Ophthalmol</RefJournal> <RefPage>114-5</RefPage> <RefTotal>Tran TH, Desauw C, Rose C. Gemcitabine-induced retinopathy in a diabetic patient. Acta Ophthalmol. 2009 Feb;87(1):114-5. DOI: 10.1111/j.1755-3768.2008.01174.x</RefTotal> <RefLink>http://dx.doi.org/10.1111/j.1755-3768.2008.01174.x</RefLink> </Reference> </References> <Media> <Tables> <NoOfTables>0</NoOfTables> </Tables> <Figures> <Figure format="png" height="972" width="774"> <MediaNo>1</MediaNo> <MediaID>1</MediaID> <Caption><Pgraph><Mark1>Figure 1: Color fundus picture depicting the whitish appearance of superficial retina with some occluded distal arterioles and some retinal hemorrhages (a: right eye; b: left eye). Venous phase of fluorescein angiogram demonstrating the distal, almost totally occluded arterioles and related capillary hypoperfusion (c: right eye; d: left eye). Optical coherence tomograhy disclosing superficial hyperreflective dots to ganglion layer infarct and severe macular edema (e: right eye; f: left eye).</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="484" width="721"> <MediaNo>2</MediaNo> <MediaID>2</MediaID> <Caption><Pgraph><Mark1>Figure 2: Color fundus picture depicting the slightly increased retinal hemorrhages and continuing retinal whitining (a: right eye; b: left eye). No OCT change is present in the right (c) and left eye (d).</Mark1></Pgraph></Caption> </Figure> <NoOfPictures>2</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>