Management of diplopia due to chemotherapy toxicity in a patient with endometrial cancer

KEYWORDS:

• Carboplatin
• diplopia
• endometrial cancer
• paclitaxel
• prism
• quality of life

Uterine cancer is one of the most common gynaecologic cancer worldwide.¹ The vast majority of cases (over 90%) are endometrial cancer, which affects mainly postmenopausal women. The average age of women diagnosed with endometrial cancer is between 60 and 70 years. Morbidity rate increases and may be associated with the decreased use of approved oestrogen-progestogen therapy.² Most endometrial cancers are adenocarcinomas and are stimulated by oestrogen, preceded by endometrial intraepithelial neoplasia.

Surgery with a total hysterectomy and salpingo-oophorectomy is the gold standard treatment for endometrial cancer. For women who develop metastatic endometrial cancer after surgical cytoreduction, postoperative adjuvant chemotherapy is often recommended. The most commonly used regimens are carboplatin plus paclitaxel or a combination of cisplatin, doxorubicin, and paclitaxel. All of these drugs can be toxic, causing many side effects, including those related to the visual system: ischaemic retinopathy, optic disc papilloedema, and peripheral neuropathy, including ocular motor and cranial neuropathies.^3,4 The latter may lead to dysfunction of eye movement and alignment that will induce diplopia. This condition can significantly reduce a patient’s quality of life and negatively influence activities in everyday life.⁵

Here is a case of a patient with endometrial cancer after surgical and chemotherapy treatment who developed double vision due to chemotherapy toxicity. Her diplopia was successfully managed.

Case report

A 76-year-old female patient was admitted to the hospital of Poznan University of Medical Sciences due to recurrence of endometrial cancer, International Federation of Gynaecology and Obstetrics stage IA in 2017. Before that in 2008, the patient had undergone surgery with total abdominal hysterectomy and bilateral salpingo-oophorectomy. As the patient was in the low-risk group, she had received no adjuvant treatment.

In 2012, she had recurrence of the disease and underwent surgery with partial tumour resection and double J stenting of the ureter. Subsequent teletherapy and brachytherapy was applied.

In 2017, progression of the disease was diagnosed with liver metastases and ascites. The patient received four cycles of chemotherapy with Paclitaxel + Carboplatin with good clinical response, but she noticed blur vision. Due to progression after 8 months, she again received Paclitaxel + Carboplatin (6 cycles) chemotherapy. Based on medical history, the patient suffered from arterial hypertension, post-chemotherapy polyneuropathy and had an episode of massive pulmonary embolism after her second surgery. Due to this, she did not receive hormonal therapy. The patient used a low dose ACE inhibitor, Enoxaparin, Pregabalin and hepatoprotective drugs.

During the 6th cycle of chemotherapy patient complained of sudden onset of double vision, which significantly affected her comfortable functioning in daily life. Contrast computed tomography of the head showed a symmetrical ventricular system, uncompressed and normally sized. The brain showed focal changes, including ischaemia and signs of bleeding. The subarachnoid spaces were normal. Bone-window images revealed no pathologies. There were no signs of extraocular muscles pathology. Bilateral CN VI palsy and orbitopathy were excluded as possible causes of diplopia.

Optometric examination showed objective refraction: RE: −1.25/-1.00 × 96; LE: −2.00/-1.25 × 104 (Righton Retinomax Screen). Subjective refraction at far showed RE: −1.75/-0.50 × 95 and LE: −2.00/-0.50 × 100; at near RE: +0.75/-0.50 × 95; LE + 0.50/-0.50 × 100 (Trial lenses, EyeGenius panel Hoya). Best corrected distance visual acuity was R&L: 6/6. Corrected near visual acuity was R: 6/6 RE; L: 6/7.5.

The unilateral cover test at distance result was 6Δ alternating intermittent comitant esotropia. At 40 cm, the cover test showed 2Δ esophoria. The patient reported seeing five lights on the Worth 4-dot test at 6 m in scotopic and photopic conditions, indicating esotropia in primary gaze, but at 40 cm she saw 4 lights (indicating fusion). Randot Stereogram testing could not be completed because of diplopia at distance but at near the stereoacuity level was 400”.

The Amsler grid test did not show any distortion nor blurred vision. Colour vision test (HRR Standard Pseudoisochromatic Test) indicated normal colour vision in each eye. Extraocular motility testing showed insignificant restricted movements (difficulty with abduction both eyes). The NSUCO test results were for saccadic 2/2/2 and for pursuit 2/3/3. Pupils were equal, round, and reactive to light. Visuoscopy revealed central fixation in both eyes. The minimum amount of relieving prism that allowed for stable sensory fusion at far was 4∆ base-out, split equally between the eyes.

Ocular health examination revealed conjunctival redness in both eyes, lid parallel conjunctival folds grade 3, clear corneas and anterior chambers, irises unremarkable, and properly positioned intraocular lenses in both eyes. Intraocular pressures were RE: 15 mmHg; LE: 16 mmHg. Posterior segment examination bilaterally showed optic discs pink with sharp margins and cup-to-disc ratio 0.4, maculae unremarkable and peripheral retina attached, Preservative-free artificial tears 4× daily (permanently) and dexamethasone drops 2× daily (for 2 weeks) were recommended.

The patient received glasses for far with prism and for near without prism. Prescribed correction for far was RE: −1.75/-0,50 × 95 with 2Δ base-out; LE: −2.00/-0,50 × 100 with 2Δ base out; and for near RE: +0.75–0.50 × 95; LE: +0.50–0.50 × 100. Based on the patient complaints, a treatment program of 1 month of home vision therapy, rehabilitation was recommended to improve the extraocular motility. She was informed that the treatment goal was to reduce her symptoms by increasing the ability to compensate for the esodeviation. Home training involved several saccadic and pursuit eye movement exercises. Pursuit eye movement therapy consisted of monocular flashlight tracking, Visual Tracking Worksheet, pencil pursuits, and Russell Ring pursuits; saccadic therapy consisted of Hart Chart column jumps.

After 1 month a follow-up eye examination was performed. The unilateral cover test at distance showed a 2∆ esophoria with prism glasses. At 40 cm, the cover test showed orthophoria. Ocular motility was full and smooth, improved from previous exam. The NSUCO test results were for saccadic 5/4/4 and for pursuit 4/4/4. Based on the previous examination of the patient results and the improvement of the eye movements, it was concluded that the decompensation of phoria was the main cause of the diplopia in this case. The minimum amount of relieving prism that allowed for stable sensory fusion at far was 3∆ base-out, split equally between the eyes. Subjectively, the patient reported that the double vision was significantly reduced and she could perform daily activities normally.

Unfortunately, after several months patient had progression of cancer with multiple liver and lung metastases and a different chemotherapy regimen was applied (Doxorubicin + Cyclophosphamide). No response to the treatment was observed and the patient died due to progression. Importantly, up to the last contact, the patient did not complain of visual symptoms.

Discussion

Patient quality of life during and after chemotherapy has become a major objective of care in oncology, as evidenced by the growing number of research studies in this field.⁵ Advances in cancer treatment extend the life of patients affected by this disease. Oncologists notice an increasing need to care not only for extending life, but also for its quality. It is worth paying close attention to changes in the visual system, which may manifest ailments such as blurred or double vision. This can significantly limit the patient performance in many activities in everyday life.

Side effects of chemotherapy involving the visual system have been published as case reports or case series. These symptoms are various. O’Brien et al. showed that carboplatin can cause optic neuropathy, transient cortical blindness, optic neuritis and blurry vision.⁶ There are no reports on the occurrence of dipliopia after chemotherapy due to phoria decompensation, but there are numerous case reports where ophthalmoplegia and orbitopathy were the direct causes of double vision.

Toxicity of intracarotid etoposide phosphate and carboplatin was reported in a 52-year old-male patient with glioblastoma multiforme.⁷ After 7 h of drug administration, it was observed that non-pupillary block angle-closure glaucoma developed secondary to uveal effusion in the ipsilateral eye (relieved by cycloplegia). Within 4 days the visual acuity worsened due to severe orbital inflammation, proptosis, optic neuropathy, and total external ophthalmoplegia.⁷

Bilateral haemorrhagic papilloedema in a female patient receiving carboplatin chemotherapy was also reported.⁸ Mulvihill et al. revealed abnormal ocular motility in 10 patients treated for intraocular retinoblastoma with 1 to 6 injections of subtenon carboplatin as part of multimodality therapy. Their conclusion was that carboplatin chemotherapy leads to mechanical restriction of eye movements.⁹

Fischer et al. described a patient with carboplatin-induced bilateral papilloedema following regular AUC-determined dose. These authors suggested that since carboplatin is widely used for a variety of common tumours in the palliative as well as the curative setting, the side effects must be kept in mind.¹⁰

Based on clinical observations made in the case report presented here, it can be concluded that not only can ophthalmoplegia and orbitopathy cause double vision, but also heterophoria decompensation. The latter side effect can be successfully managed.

Conclusions

A possible side effect of chemotherapy in endometrial cancer patients is double vision, which can be successfully managed with prismatic correction and in-home visual exercises. It is very important to recognise potentially severe side effects of chemotherapy before irreversible damage occurs. Sustaining good quality of life for cancer patients requires comprehensive eye care and a multidisciplinary approach.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu [500/19].