Download Julie McLaughlin

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