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Julie McLaughlin, OD and Hardeep Kataria, OD Baltimore VAMC Residents 2012-2013 AAO Residents Day Abstract This case report evaluates bilateral cystic maculopathy and its association with the “fluid retention syndrome,” secondary to use of anti-cancer treatment, Docetaxel. It also evaluates the likelihood of other mechanisms to explain the cystic maculopathy. Abstract: 1. Case History a. Patient demographics i. 65 year old Caucasian male b. Chief complaint i. “can’t see small print at near” c. Past Medical history i. Diabetes Mellitus ii. Hypothyroidism iii. Chronic hepatitis C iv. High grade Soft tissue sarcoma 1. Diagnosed 05.2011 v. Hyperlipidemia vi. GERD vii. Diverticulitis d. Past Ocular History i. Glaucoma suspect versus physiological cupping OU - no h/o drops - no history of prostaglandin use - no history of topical steroid use - oral steroid use? Still pending confirmation by patient ii. h/o of TIAs ii. Cataracts iii. Recent Eyelid laceration - treated with Neosporin ointment iv. Negative history of ocular inflammation e. Medications i. Levothyroxine ii. Docusate sodium iii. Neosporin ointment iv. Docetaxel (treatment initiated May 2011) 2. Pertinent Findings a. Clinical i. VA @ Distance OD: 20/50, OS: 20/50 ii. Manifest OD: +1.00-1.25x100 20/50+2 OS: +1.50-0.75x070 20/50 ADD: +3.00 NVA .50M@ 12inches iii. Confrontation fields: FTFC OU iv. Pupils: PERRL –APD OU v. Lids/lashes/lacrimals: scab through right eyebrow w/ cyanoacrylate vi. Conjunctiva: white and quiet OU vii. Cornea: clear OU viii. AC: D&Q OU ix. Iris: wnl, no nvi OU x. Lens OD: 1+ACC,2+NS, 1+PCC, no PSC OS: tr ACC, 2NS, no PSC xi. Tonometry - 14mmhg OU xii. C/D: OD .6 / OS .6 xiii. Macula: clear OU xiv. Vessels: normal OU xv. Periphery: unremarkable OU xvi. OCT of Macula: bilateral macular edema b. Physical i. Significant swelling of lower legs c. Radiology studies: i. PET scan 06.29.12 a. There is metabolically bilateral pleural effusion and ascites with background activity. ii. MRI BRAIN with and without contrast 04.25.12 a. Chronic small vessel ischemic disease. iii. PET 03.23.12 a. Three stable, metabolically inactive right lung nodules b. Consistent with soft tissue sarcoma iv. PET 01.11.12 a. Hypermetabolic pulmonary nodules; r/o metastasis vs infection b. Splenic lesion with abnormal appearance v. PET 05.02.11 a. Mesenteric edema with two hypermetabolic abdominal lesions suggestive of neoplastic disease b. New presentation of 3 right side lung nodules, c. Chemotherapy initiated after this diagnosis vi. PET performed post chemo 09.2011 a. Progression of malignancy with new hypermetabolic lesions in the mesentery c. Laboratory Studies vii. With Docetaxel, LFTs (can increase liver enzymes) (5) a. AST (SGOT): 51H b. AST (SGPT): 37 c. ALK PH: 78 d. ALB: 2.7 L e. PROTEIN, TOTAL: 5.5L f. TOTAL BILIRUBIN: 0.7 viii. Docetaxel can lower WBC, RBC and PLT (5): a. RBC: 4.16L b. WBC: 3.5L c. HGB: 9.9L d. HCT: 30.6L e. MCV: 7.3.6L f. MCH: 23.8L g. MCHC: 32.4L h. PLT: 75L i. PTT: 12.7 ii. INR: 1.13 i. NEUTROPHIL %: 9.1L j. LYMPHOCYTE: 55.6%H k. MONOCYTES: 33.0%H l. BASOPHIL: 1.1% Other pertinent lab findings: a. Glucose ANC 102 b. TSH: 11.68H 3. Differential Diagnosis a. CME 2/2 Docetaxel use b. CSME 2/2 Diabetes Mellitus Type II c. Hepatitis C retinopathy without the use of interferon therapy (6) 4. Diagnosis and Discussion a. Bilateral vision loss due to cystoid macular edema (CME) most likely associated with Docetaxel therapy b. OCT findings of CME OU c. Peripheral leg edema observed on exam and pleural effusion noted on PET scan on 6.29.2012 d. Findings consistent with the Fluid Retention Syndrome as described in the literature 5. Treatment, Management a. Oral acetazolamide 50mg BID PO (initiated7.13.12) b. NSAID QID OU ( initiated 7.9.12) c. Literature review: Docetaxel is used to treat prostate, ovarian, breast and non small cell lung cancer (1, 2, 3). Its function is to facilitate malignant cell apoptosis by binding beta tubulin and restricting microtubule mobility and therefore arresting cell mitosis (1). Docetaxel has been documented to cause pleural effusion and peripheral edema, with which our patient also presents. This might be associated with the “fluid retention syndrome,” which hypothesizes that increased capillary fluid filtration and perfusion of proteins leads to edema. Some have proposed that this might be the mechanism responsible for cystoid macular edema that has been related to Docetaxel use. However, the cystic maculopathy that is associated with Docetaxel use presents without leakage of fundus fluorescein angiography (FFA), suggesting that the mechanism is dissimilar to that which occurs in cystoid macular edema secondary to capillary leakage. It suggests that: either the leakage is too slow to be detected by FFA; the blood-retinal barrier is selective to molecules larger than fluorescein; or a subsequent swelling of retinal Mueller cells secondary to a Docetaxel toxicity is the likely mechanism. The latter is similar to the mechanism suggested for niacin maculopathy (4) or CME associated with retinal dystrophies such as Retinitis Pigmentosa, Goldman-Favre disease, and juvenile retinoschisis. It is also possible that both mechanisms are occurring simultaneously, systemic capillary hyperpermeability and ocular toxicity to Mueller cells with subsequent intracellular edema. Studies have evaluated the dosages of Docetaxel: 100mg/m2 -400mg per month (1,2,3) and found that symptoms began after 2 months (3). These mainly include peripheral edema and nonmalignant effusions, especially with a dosage of 400mg (2). To date the only promising treatment reported in a few case reports consist of discontinuation of Docetaxel and subsequent therapy with Diamox. It is possible that mechanisms might be delineated by the response to the type of treatment. For example, treatment with corticosteroids provides evidence that the pathway may either be an inflammatory hyper permeability of the capillaries or an inflammatory response (2). Similarly, treatment and adequate response with NSAIDs might suggest an anti-inflammatory mechanism. Additionally, treatment with Diamox suggests an interaction between protein content in plasma and filtration. Its function is to alter the osmotic gradient at the RPE and increase fluid transport via active transport at the cellular level. This also causes a re-acidification of the RPE, which might suggest an interaction of the edema at the level of the RPE. Other ocular side effects of Docetaxel that have been reported include punctal stenosis and subsequent excessive tearing 6. Conclusion a. Our findings are consistent with the only two case reports of Taxotere toxicity reported in the literature b. Awaiting additional testing and follow-up post NSAID/Diamox use i. Additional testing will help delineate the mechanism of the CME References: 1. Telander DG, Stein J. Cystoid Macular Edema with Docetaxel Chemotherapy and the Fluid Retention Syndrome. Seminars in Ophthalmology, 2007;22:151-153. 2. Semb KA, Aamdal S, Oian P. Capillary Protein Leak Syndrome Appears to Explain Fluid Retention in Cancer Patients Who Receive Docetaxel Treatment. J Clin Oncol. 1998 Oct;16(10):3426-32. 3.Teitelbaum BA, Tresley DJ. Cystic Maculopaty with Normal Capillary Permeability Secondary to Docetaxel. Optometry and Vision Science,2003;VOL.80.NO.4,PP.277-279 4. Dajani HM, Lauer AK. Optical Coherence Tomography Findings in Niacin Maculopathy, Can J Ophthalmol, 2006;41:197-200 5. http://www.cancer.org/Treatment/TreatmentsandSideEffects/GuidetoCancerDrugs/docetaxel 6. Ocular Manifestations of Hep. C viral infection. Curr Opin Ophthalmol, 2002 Dec;13(6):423-7