Abstract
Purpose: To describe a case of presumed Purtscher-like retinopathy in association with 2 chemotherapies. Methods: A retrospective chart review was performed. Results: A 40-year-old Black woman was diagnosed with pancreatic adenocarcinoma with metastasis to the liver. Cotton-wool spots and microaneurysms (dot/blot hemorrhages) were found on a routine examination 1 month after the patient started gemcitabine/paclitaxel. An increase in cotton-wool spots was noticed after she stopped gemcitabine/cisplatin therapy and started 5-fluorouracil/irinotecan/leucovorin therapy. These retinal changes were observed until the time of death. Conclusions: We believe that the Purtscher-like retinopathy began with gemcitabine toxicity but that the irreversible damage was the result of cisplatin chemotherapy. The patient’s uncontrolled hypertension and type II diabetes likely put her at greater risk for developing this retinopathy.
Keywords: Purtscher-like retinopathy, Purtscher retinopathy, retinopathy, chemotherapy toxicity, gemcitabine, cisplatin, diabetes, hypertension, cotton-wool spots, microaneurysms
Introduction
Purtscher retinopathy is most commonly associated with compression trauma; however, when symptoms are observed without trauma occurring, the term Purtscher-like retinopathy is used. This can be associated with conditions such as acute pancreatitis, renal failure, and crush injuries as well as chemotherapy toxicity. This retinopathy presents with multiple white retinal patches, or cotton-wool spots, and numerous small hemorrhages. 1
We present a case of Purtscher-like retinopathy in association with the drugs gemcitabine (Gemzar, Eli Lilly and Co), a nucleoside analogue, and cisplatin, an alkylating agent. Although gemcitabine has been associated with Purtscher-like retinopathy as well as other ocular complications,2–4 we were unable to find reports linking cisplatin therapy directly to Purtscher-like retinopathy.
Here, we report a patient who was receiving chemotherapy to treat pancreatic adenocarcinoma, a systemic condition that has also been reported to be associated with Purtscher-like retinopathy in treatment-naïve patients. 1
Case Report
A 40-year-old Black woman presented to our practice on August 29, 2017, with scattered cotton-wool spots and scant dot/blot hemorrhages in both eyes unrelated to her underlying mild nonproliferative diabetic retinopathy (NPDR). She had been diagnosed with longstanding hypertension, hyperlipidemia in June 2017, and stage 4 pancreatic adenocarcinoma with metastasis to the liver in December 2015. She was treated with various rounds of chemotherapy (Table 1).
Table 1.
Chemotherapy Regimens and Dates Administered.
| Date | Chemotherapy |
|---|---|
| January 20, 2016 | 5-fluorouracil + leucovorin + irinotecan + oxaliplatin |
| December 21, 2016 | Gemcitabine + paclitaxel |
| March 1, 2017 | Gemcitabine + cisplatin |
| June 28, 2017 | 5-fluorouracil + irinotecan liposome + leucovorin |
| August 22, 2017 a | 5-fluorouracil + irinotecan liposome + leucovorin |
Last chemotherapy treatment.
In January 2017, 1 month after starting gemcitabine/paclitaxel (Abraxane, Abraxis BioScience, LLC) therapy, the patient was seen by her referring ophthalmologist for a routine examination to monitor her mild NPDR. Two new cotton-wool spots were noted in the right eye; the spots were not present at the initial optometry appointment in July 2016. The patient was told to return for a routine follow-up in 6 months.
Between follow-up appointments, the patient’s chemotherapy regimen changed to gemcitabine/cisplatin. At the routine follow-up 5 months later, an examination showed a significant increase in cotton-wool spots and dot/blot hemorrhages in both eyes. She was then referred to our practice.
At her initial presentation at our practice, the patient had a corrected distance acuity of 20/30+1 OD and 20/25−2 OS; the intraocular pressure was 15 mm Hg in both eyes. She reported no subjective ocular symptoms. The anterior examination was normal, while the dilated posterior fundus examination showed mild scattered dot/blot hemorrhages with no neovascularization elsewhere as well as scattered peripapillary cotton-wool spots in both eyes. Optical coherence tomography imaging (Figure 1) showed retinal pigment epithelium changes with no evidence of macular edema. Advanced imaging (Figure 2) showed microaneurysms (dot/blot hemorrhages) throughout with some peripheral capillary dropout and capillary nonperfusion in areas of cotton-wool spots bilaterally.
Figure 1.
Optical coherence tomography (OCT) imaging showed changes in the retinal pigment epithelium with no evidence of macular edema in either the right eye (shown) or left eye. Cotton-wool spots were noted near the optic nerve, as seen above. Findings were bilateral.
Figure 2.
Fundus examination (A) shows multiple cotton-wool spots and scattered dot/blot hemorrhages (microaneurysms) in the midperiphery. Fluorescein angiography (FA) (B and C) shows microaneurysms 360 degrees, staining of drusen, and peripheral capillary dropout. Capillary nonperfusion was seen in areas of cotton-wool spots. FA also shows hypofluorescence in areas of cotton-wool spots (B), with late (C) hyperfluorescence. All images in this figure are of the right eye; however, the findings are bilateral.
The patient’s last laboratory results (August 28, 2017) showed low hemoglobin (7.7 g/dL) consistent with anemia and low creatinine (0.54 mg/dL), while her blood glucose, blood urea nitrogen, aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), alanine aminotransferease (serum glutamic-pyruvic transaminase), and platelets were all within normal range. The patient died 1 month after examination, on September 30, 2017. Because of these findings as well as the cotton-wool spots being more copious than expected, the patient was diagnosed with Purtscher-like retinopathy in both eyes with cotton-wool spots related to chemotherapy.
Conclusions
We believe that our patient developed Purtscher-like retinopathy secondary to a combination of gemcitabine and cisplatin chemotherapies. The patient first presented with cotton-wool spots in addition to microhemorrhages after starting gemcitabine/paclitaxel, indicating the retinal changes started with the gemcitabine chemotherapy. She was then treated for 3 months with gemcitabine/cisplatin combination therapy. Even 1 month after cessation of gemcitabine/cisplatin, the referring ophthalmologist noticed an increase in cotton-wool spots and dot/blot hemorrhages.
Approximately 2 months after cessation of the chemotherapy, we examined the patient and observed that there was still substantial evidence of bilateral Purtscher-like retinopathy with underlying mild NPDR. Because the retinal changes were evident after discontinuing both gemcitabine and cisplatin, we believe the retinopathy began with gemcitabine but that the irreversible damage was caused by the cisplatin chemotherapy.
When considering ocular toxicity of chemotherapy in the posterior segment of the eye, the retinopathy and neuropathy presentation is usually bilateral and irreversible, depending on the chemotherapy agent(s). 5 Research has shown cisplatin is highly toxic and has potentially harmful ocular side effects, including vision loss with bilateral central scotomas. Katz et al 6 reported a case of retinal toxicity from cisplatin that was dose dependent; thus, it could be harmful to photoreceptor cells.
Cisplatin can cause retinal toxicity in the forms of pigmentary changes (maculopathy), cone dysfunction, and mild retinal ischemic alterations such as cotton-wool spots and hemorrhages, which are key factors in Purtscher-like retinopathy. A case reported by Kwan et al 7 showed that cisplatin can cause ischemic retinopathy with neovascularization, most likely as the result of a vaso-occlusive process. In that case, the damage was irreversible and vision did not return to normal after cessation of the chemotherapy.
Like cisplatin, gemcitabine is a chemotherapeutic drug that is toxic to the retina and can cause visual changes and retinal alterations. In contrast, the ocular side effects of gemcitabine are reportedly reversible, with visual changes tending to improve after cessation of the drug. Although gemcitabine is known to be a well-tolerated drug, it has many potential side effects, including vascular toxicity and bilateral vision loss resulting from Purtscher-like retinopathy. Multiple case studies also show that diabetes and hypertension can increase a patient’s risk for developing Purtscher-like retinopathy from gemcitabine.2–4
Not only can gemcitabine cause retinal disease, it can cause renal issues as well. In a case reported by Sheyman et al, 4 a patient presented with Purtscher-like retinopathy and required hemodialysis for developing end-stage renal disease after treatment with gemcitabine. Gemcitabine has also been shown to cause not only retinal and renal ischemia but also myocardial ischemia, which can cause myocardial infarction.
The vaso-occlusive process can lead to Purtscher-like retinopathy but can affect other parts of the body as well. In a case reported by Banach and Williams, 8 a patient on gemcitabine therapy presented with Purtscher-like retinopathy in both eyes and developed progressive ischemic peripheral vaso-occlusive disease, which led to digital necrosis bilaterally. An upper-extremity arteriogram showed bilateral inadequate palmar arterial flow, and laboratory results showed an elevated erythrocyte sedimentation rate and elevated antinuclear antibody ratio. These values returned to within normal limits after the gemcitabine was discontinued.
In conclusion, we believe that patients treated with chemotherapy, especially gemcitabine, cisplatin, or a combination, should be monitored for retinal changes that could lead to vision loss. Patients treated with these drugs who are diabetic and/or have hypertension or other risk factors should be made aware that these drugs put them at greater risk for developing Purtscher-like retinopathy during treatment. Patients should be informed of the possible ocular side effects of chemotherapy. They should also be informed that gemcitabine and cisplatin could lead to vaso-occlusive disease, which can potentially lead to ocular side effects as well as other adverse events, such as necrotizing vasculitis, nephropathy, and myocardial infarction.
Acknowledgments
The authors thank Mike Pulley, an English professor at Clemson University, for assisting in the editing of this paper.
Footnotes
Ethical Approval: This report was conducted according to the principles of the Declaration of Helsinki and all protected healthcare information was established according to Health Insurance Portability and Accountability Act (HIPAA) compliance rules. Institutional Review Board (IRB) approval is not required for 3 or less patients.
Statement of Informed Consent: Informed consent was obtained upon initial admission of patient to the practice regarding use of personal information for research.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
References
- 1.Tabandeh H, Rosenfeld PJ, Alexandrakis G, Kronish JP, Chaudhry NA. Purtscher-like retinopathy associated with pancreatic adenocarcinoma. Am J Ophthalmol. 1999;128(5):650-652. doi: 10.1016/s0002-9394(99)00204-4 [DOI] [PubMed] [Google Scholar]
- 2.Kovach JL. Gemcitabine-induced retinopathy. Retin Cases Brief Rep. 2018;12(3):240-241. doi: 10.1097/icb.0000000000000471 [DOI] [PubMed] [Google Scholar]
- 3.Tran THC, Desauw C, Rose C. Gemcitabine-induced retinopathy in a diabetic patient. Acta Ophthalmol. 2009;87(1):114-115. doi: 10.1111/j.1755-3768.2008.01174.x [DOI] [PubMed] [Google Scholar]
- 4.Sheyman AT, Wald KJ, Pahk PJ, Freund KB. Gemcitabine associated retinopathy and nephropathy. Retin Cases Brief Rep. 2014;8(2):107-109. doi: 10.1097/icb.0000000000000015 [DOI] [PubMed] [Google Scholar]
- 5.Omoti AE, Omoti CE. Ocular toxicity of systemic anticancer chemotherapy. Pharm Pract (Granada). 2006;4(2):55-59. doi: 10.4321/s1885-642x2006000200001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Katz BJ, Ward JH, Digre KB, Creel DJ, Mamalis N. Persistent severe visual and electroretinographic abnormalities after intravenous cisplatin therapy. J Neuroophthalmol. 2003;23(2):132-135. doi: 10.1097/00041327-200306000-00005 [DOI] [PubMed] [Google Scholar]
- 7.Kwan AS, Sahu A, Palexes G. Retinal ischemia with neovascularization in cisplatin related retinal toxicity. Am J Ophthalmol. 2006;141(1):196-197. doi: 10.1016/j.ajo.2005.07.046 [DOI] [PubMed] [Google Scholar]
- 8.Banach MJ, Williams GA. Purtscher retinopathy and necrotizing vasculitis with gemcitabine therapy. Arch Ophthalmol. 2000;118(5):726-727. doi: 10.1001/archopht.118.5.726 [DOI] [PubMed] [Google Scholar]