DOI: https://doi.org/10.21203/rs.2.9465/v1
Paclitaxel is a member of the taxane family used in various chemotherapeutical protocols for the treatment of ovarian cancer, lung cancer and breast cancer.[1] They are mitotic inhibitors, preventing normal reorganization of the microtubule network within cells [2]. Side effects of the drug are involving neurological disorders as also diseases of the eye. Bone marrow suppression, vomiting, alopecia and nausea have been described as systemic side effects. More rarely are ophthalmic side effects of the drug. A bilateral cystic macula edema with no leakage in fluorescence angiography is a rare side effect of Paclitaxel[3, 4] . Other retinal diseases demonstrating a cystoid macular edema with non-angiographic leakage are juvenile X-chromosomal Retinoschisis, Goldman-Favre Syndrome, several forms of Retinitis pigmentosa as also Niacine toxicity of the macula[5-11] . Anatomical restauration and vision increase have been described after cessation of the drug, but also non-vision increase has been reported [1, 3, 4, 12-34].
We report the case of 59-year-old female presenting with gradual bilateral vison loss. The patient was treated with adjuvant Paclitaxel chemotherapy for ovarian cancer and had received 21 cycles from 6/17 to 12/17. The cumulative dose of the drug was 2708 mg. Systemic diseases as diabetes and hypertension were not reported. Cataract surgery of both eyes was performed two years ago. Also, childhood strabism resulting in amblyopia of the right eye was reported.
Other diseases of the eye or surgeries were not reported. The visual acuity of both eyes was 0.5 at the initial presentation and did not improve through the use of lenses. No vision disturbing anomalies of the anterior eye section were seen on examination. Funduscopy of the retina revealed a macular edema (Fig.1). The eye pressure was in the normal physiologic range.
Spectral domain coherence tomography (OCT) (Heidelberg Spectralis OCT, Heidelberg GmbH, Heidelberg, Germany) scans revealed an increased bilateral macular thickness due to intraretinal fluid accumulation (Fig.4,5). Despite the OCT results demonstrating a cystoid maculopathy, the fluorescence angiography (FA) (Heidelberg Spectralis , Heidelberg GmbH, Heidelberg, Germany) (Fig.7-8) as also the indocyanine angiography (ICG) (Fig.9-10) showed no leakage and therefore no impairment of the blood retinal barrier. These results are consistent with the diagnosis of a cystoid macula edema without leakage. Fundus autofluorescence disclosed no pathologies (Fig. 6). Microperimetry of both eyes (MAIA-microperimetry, Centervue, Padua, Italy) confirmed the visual deficits on a functional basis. Fixation problems of both eyes were detected as also a decreased sensitivity shift (Fig. 2,3).
Bilateral paclitaxel induced non-leaking maculopathy was diagnosed and chemotherapy treatment was discontinued. Five weeks after chemotherapy discontinuation, the vision increased to 0.6 on the right eye and 1.0 on the left eye. OCT disclosed the complete anatomical resolution of the previous presented macular edema (Fig. 11). Microperimetry showed also the functional restauration of the fovea (Fig. 12, 13) as also a panel D-15 color test (Fig. 14). Microperimetry demonstrated an increased sensitivity of the fovea to the stimuli and a normal fixation performance. A later clinical control 9 weeks after chemotherapy cessation showed also a further vision increase of the amblyopic right eye to 0.8. The vision of the left eye stabilized at 1.0.
The differential diagnosis for cystoid macula edema without angiographic leakage includes nicotinic acid- associated maculopathy, X-linked juvenile retinoschisis, various forms of retinitis pigmentosa and taxane-associated maculopathy [3, 6-11, 13, 14, 17, 22, 33, 34].
Taxane are a group of chemotherapeutic drugs that are used to treat several malignancies such as breast, lung and ovarian cancer. Paclitaxel (Taxol) is a microtubule-stabilizing agent which belongs to the Taxane family [35]. A bilateral, angiographically non-leaking cystoid macular edema is a seldom side effect of the drug especially after high cumulative doses. Imaging in Paclitaxel-related CME reveals fluid on ocular coherence tomography scan without leakage on fundus fluorescein angiography, which is in keeping with our findings. There are no recommended treatment guidelines for this condition because of the unclear mechanism of pathology. Treatment strategies have focused on Paclitaxel cessation, which appears to result in spontaneous resolution of CME and improvement in visual acuity [13, 15, 16, 22, 26, 32].
Color vision and microperimetric function of the fovea display other values characterizing foveal function. Until now, these parameters have not been evaluated after cessation of Paclitaxel.
Our group used for the first time microperimetry to evaluate the effects on paclitaxel on macular function. We were able to demonstrate fixation loss, loss of fixation stability as also macular sensitivity by Paclitaxel therapy for ovarian cancer. All parameters returned to normal after Paclitaxel cessation. These functional improvements demonstrate the importance to identify Paclitaxel maculopathy in early stages and initiate directly the cessation of the drug to improve vision and macular function.
OCT: ocular coherence tomography, CME: cystoid macula edema, ICG: indocyanine green angiography
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Authors’ contributions:
SH participated in the design of the study and wrote the manuscript. DG, PS,SM conceived the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
Consent for publication:
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Competing interests:
The authors declare that they have no competing interests.