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Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 739-746

Ocular metastasis of primary gynecological malignancies, a rare but not insignificant entity: A systematic review

Gynecologic Oncology Unit, 1st Department of Obstetricsa and Gynecology, National and Kapodistrian University of Athens, Athens, Greece

Date of Submission23-Aug-2021
Date of Acceptance25-Mar-2022
Date of Web Publication16-Jun-2022

Correspondence Address:
Dr. D E Vlachos
80 Leoforos Vasilisis Sofias Str, 11526, Athens
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njcp.njcp_1763_21

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The genital system remains one of the most common sites of carcinogenesis in women. Advances in surgery, radiation treatment, and chemotherapy have increased their efficacy and many patients survive for many years after their initial diagnosis. The eye is a rare site of metastasis from gynecological cancer due to its distant location from the genitalia. In this systematic review, we retrieved all case reports of patients with ocular metastasis from gynecological neoplasms. The demographic, clinical, and treatment characteristics were retrieved and analyzed. A total of 70 case reports were included. Forty-eight of these reports concerned patients with a known malignancy that recurred in the eye and in 22 patients' ocular symptomatology accompanied the initial diagnosis of the gynecologic malignancy. 73.9% of these patients exhibited concomitant metastasis to other organs. The mean disease-free interval was found at 25.7 months and mean survival time after the eye metastasis was 13.5 months. Refractory disease was identified as the most important risk factor associated with mortality. Because eye metastasis has such a dismal prognosis, all gynecologists who treat oncological patients should be highly suspicious for reported eye complaints.

Keywords: Eye, gynecological malignancies, metastasis, orbit

How to cite this article:
Vlachos D E, Thomakos N, Haidopoulos D, Pergialiotis V, Theodoulidis V, Protopapas A, Rodolakis A. Ocular metastasis of primary gynecological malignancies, a rare but not insignificant entity: A systematic review. Niger J Clin Pract 2022;25:739-46

How to cite this URL:
Vlachos D E, Thomakos N, Haidopoulos D, Pergialiotis V, Theodoulidis V, Protopapas A, Rodolakis A. Ocular metastasis of primary gynecological malignancies, a rare but not insignificant entity: A systematic review. Niger J Clin Pract [serial online] 2022 [cited 2022 Jun 28];25:739-46. Available from:

   Introduction Top

According to the 2020 Global Cancer Observatory Annual Report, the genital tract is the second most frequent site of carcinogenesis in women with 1,398,601 newly diagnosed cases and 671,875 fatalities.[1] Gynecological malignancies exhibit 3 patterns of spread: first, by local expansion to the adjuvant organs or the peritoneal cavity; second, by expansion to the locoregional lymph nodes; and third, by expansion via bloodstream to distal organs. The pattern of spread varies depending on the primary site of origin, the histological type, and the grade of a tumor. Hematogenous dissemination occurs frequently by poorly differentiated tumors in the liver, pleura, and lungs.

Ocular malignancies are rare, and the most common primary malignancies of the eye are uveal melanoma, vitreoretinal lymphoma, and rhabdomyosarcoma.[2] Secondary malignant lesions to the orbit are more frequent than the primary.[3] Two major surveys have reported that their incidence varies from 2%–7%, and they mainly originate from lung, breast, and prostate carcinomas.[4] Choroidal metastasis is more common than the orbital (86% vs. 12%, respectively). The reported median survival after the identification of eye metastasis is 6.5 months.

In the international literature, there are sporadic case reports (CRs) and literature reviews on the metastasis of gynecological cancer to the eye. This paper represents a comprehensive systematic review of the literature presenting data regarding the dissemination of gynecological malignancies to the eye to analyze the patterns of the disease.

   Materials and Methods Top

Study design

This systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We performed an electronic database search for CRs of gynecological cancer patients (breast cancer patients excluded) who developed metastasis to the different anatomical parts of the eye and orbit. We searched PubMed using the terms “Eye,” “Uvea,” “Choroid,” “Iris,” “Ciliary Body,” “Retina,” “Sclera” and “Uterine Neoplasms,” “Endometrial Cancer,” “Endometrial Neoplasms,” “Cervical Cancer,” “Uterine Cervical Neoplasms,” “Ovarian Cancer,” “Ovarian Neoplasms,” “Choriocarcinoma,” and “Gestational Trophoblastic Neoplasia.” Scopus and Google Scholar were also searched using the same terms. All the articles that met or were presumed to meet the inclusion criteria were retrieved in full text. Also, the reference lists from the retrieved studies were utilized for retrieving similar reports. Full papers as well as abstracts were read [Figure 1].
Figure 1: Prisma Flow Diagram

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We extracted the following data from the collected CRs: age, primary or recurrent disease, number of recurrences until eye metastasis, affected side (left, right, bilateral), ocular symptoms, pain, fundoscopic findings, ocular pressure, affected part of the eye, main symptom, duration of the disease before the diagnosis of eye metastasis, histological type, grade, concomitant metastasis to the brain or the spinal cord, histological type and grade, diagnostic test utilized for the diagnosis, fundoscopic findings, treatment utilized for the eye metastasis, response to treatment, chemotherapy scheme that was utilized, and survival after the diagnosis of ocular involvement. The main summary measure was the overall survival of the patients.


The clinicopathological characteristics of each case report were tabulated in a Microsoft® Excel spreadsheet. The results were expressed as mean values (SD) or as median values (interquartile range). Qualitative variables were expressed as absolute and relative frequencies. Life table analyses were used to calculate cumulative survival rate (standard errors) for specific time intervals. The prognostic value of each variable for survival was assessed by the log-rank test, as well as the Cox proportional hazards regression analysis. Kaplan–Meier survival estimates for events were graphed over the follow-up period. All reported P values are two-tailed. Statistical significance was set at P < 0.05, and all analyses were conducted using SPSS statistical software (version 27.0) on a standard IBM personal computer.

   Results Top

In [Table 1] and [Table 2], the demographic and the clinical characteristics of the patients are presented. As shown, a total of 70 CRs published between the years 1959–2021 in America (42.9%), Asia (32.9%), Australia (1.4%), Europe (20%), Japan (1.4%), and South Korea (1.4%) were included in the present analysis, with the mean age of patients being equal to 47.7 years (SD = 16.1 years).[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74] Most of the studies (68.6%) examined recurrence of malignancy, and in most of the examined CRs, 71.1% was the first recurrence. Overall, 46.4% of the patients were diagnosed with metastatic cancer on their left eye, and 39.1% of patients on the right eye. Choroid (54.3%) was the most frequent part of the eye diagnosed with metastatic cancer. Regarding the symptoms, loss of vision was reported in 35% and pain in 32.9% of the patients. Furthermore, 40.5% of the patients had impaired ocular movement, 47.3% of the patients had retinal detachment, 47.8% of the patients were diagnosed with elevated ocular pressure on the right eye, while 76.9% of the patients were diagnosed with elevated ocular pressure on their left eye.
Table 1: Demographic and clinical characteristics

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Table 2: Clinical characteristics

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As depicted in [Table 3] and [Table 4], 72.5% of the patients were diagnosed primarily at stage 4, and 66.7% of the patients were diagnosed with a grade 3 malignancy. Concomitant metastasis occurred in 73.9% of the patients, and the most frequent site was the lungs (47, 14%). As far as the response of the eye metastasis to the applied treatment, 58.8% of the patients presented complete response and 26.5% of the patients presented partial response; 43.2% and 29.7% of the patients presented complete and partial response, respectively. Ocular symptoms were predominant on 76.5% of the patients, while it was the initial symptom of recurrence on 60.9% of patients.
Table 3: Tumor characteristics

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Table 4: Treatment Characteristics

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[Figure 2] and [Figure 3] summarize the overall survival, both in the total sample and the subgroups according to the type of disease and the diagnosis of another metastasis. During the follow-up period, 37/47 of the patients died (78.7%), and the mean survival time in the total sample was 13.5 months (95% CI = 8.2–18.9 months). No significant difference was observed according to the type of disease (P = 0.834) and the diagnosis of other metastasis (P = 0.285). Patients with refractory disease had 8.37 times greater hazard as compared to those with complete response, while the progression-free survival, stage, and grade were not found to be significantly associated with survival. The cumulative survival rate for the first 6 months was 38% (SE = 7.0%), for 1 year 31% (SE = 7.0%), for 2 years 25% (SE = 7.0%), and for 3 years 16% (SE = 7.0%) [Figure 2].
Figure 2: Kaplan Meier curve of overall survival

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Figure 3: Kaplan Meier curve of overall survival associated with the type of disease

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Cervical cancer

Twenty-four patients were diagnosed with ocular metastasis from malignancies of the uterine cervix. The median age of the patients was 48 years, and the most common histological type was squamous cell carcinoma (16/24 CRs). Most metastases were located at the orbit of the eye (14/24), followed by the choroid (8/124), and both sides were equally affected. Interestingly, in 8 patients, the eye symptoms were the initial symptoms of the disease. In the rest 16, the median disease interval was 24.88 months (range: 6–120 months). Fourteen patients with eye metastases showed metastases to other sites, primary to the lung and secondary to the paraaortic and supraclavicular lymph nodes. The median overall survival was 5.56 months.

Ovarian cancer

Fifteen CRs concerning ovarian cancer patients were obtained during our literature review. Fourteen cases of epithelial ovarian cancer patients and 1 case of ovarian choriocarcinoma were included. The median age was 52.13 years (range: 28–80 years). Four of the cases had ocular metastases at the time of their primary diagnosis. In the 11 patients with recurrent ovarian cancer, the median interval from primary diagnosis to developing eye metastasis was 36.42 months (range: 8–120 months), and it developed during their first recurrence in the majority of the cases (7/11). The left eye was mostly affected (7/14 CRs). The choroid plexus was affected in 12/15 cases, and in the rest of the cases, the orbit was affected. Concomitant metastasis was found in 12 cases, mostly the lungs (5/12). Median survival after the diagnosis of the ocular metastasis was 14 months (range: 1–48 months).

Endometrial cancer

We retrieved 14 CRs reporting metastases on endometrial carcinoma patients. The median age was 59.64 years (range: 31–87 years), and in most cases, the right eye was affected (8/14). Three CRs concerned newly diagnosed patients, and in 2 of the cases, the eye symptomatology was the initial symptom. Median duration of recurrence was 29.6 months (range: 3–108 months). In two CRs, the metastases affected the orbit and the retina, and in 7 CRs, the uvea was affected. No special predilection to the histological subtype was observed. The mean survival time after diagnosis of eye metastasis was 2 months.


Interestingly, 14 CRs of choriocarcinoma patients were retrieved. The patients had a mean age of 3 years (range: 17–43 years). In half of the CRs (7/14), eye metastasis was concomitantly diagnosed with the initial diagnosis of the primary disease. In recurrent cases, the relapse was diagnosed after a median of 17 months (range: 12–120 months). Choroid plexus was the most commonly affected site (13/14), and lungs (13/14) was the most common site of concomitant metastasis.

Uterine sarcomas

We retrieved 3 CRs of uterine sarcomas patients, involving 2 leiomyosarcoma and 1 low-grade endometrial stromal sarcoma patient. Median age was 57 years (range: 46–63 years). Two cases of orbital and 1 of choroidal metastasis were identified in the context of recurrence.

   Discussion Top

The eye is a complex sensory organ that is composed of three layers: the corneoscleral coat, the uvea, and the retina. The cornea and sclera form the hard outer cover of the eye. The retina is the neurosensory layer of the eye responsible for eyesight, while the uvea consists mainly the choroid, i.e., the vascular layer responsible for the blood supply of the eye. The choroid plexus is created by the extensive branching of the retinal vessels after they penetrate the eyeball with the optic nerve.[75]

Contrary to the orbit, the eye is devoid of lymphatic channels, and ocular metastatic lesions are of hematogenous spread.[3],[76] As with brain metastasis, the tight capillary network of the choroid plexus decelerates blood flow, thus, facilitating the implantation of circulating tumor cells.[77] Macula and the paramacular area exhibit the densest capillary network of the retina, which explains the higher rates of metastasis in these regions. Iris metastasis is the most uncommon with reported rate of 7.8%, while the orbit and optical nerve are affected in 12.3% and 1.3% cases, respectively.

In our review, most of the cancer types had a predilection of metastasis to the choroid plexus, except cervical cancer. In our study, 38/70 (54.3%) of patients developed choroidal metastasis. Choriocarcinoma patients exhibited the biggest predilection in creating choroidal lesions. Although gestational trophoblastic neoplasia is a rare malignancy, we retrieved 14 relevant CRs. In all of the cases, there are multiple organs affected. This indicates the potential capability of these tumors for hematogenous dissemination. Interestingly, 14/24 (58.3%) cervical cancer patients developed orbital metastasis. We estimate that this is due to the enhanced intratumoral lymphangiogenesis of squamous cell carcinomas.

The symptoms of the affected patients depend on the location of the tumor and progress rapidly due to the fine histologic elements of the oculus and the orbital confined space. The patients usually complain of impaired vision, restriction of the visual field, and proptosis. The development of the tumor inside the retina can cause detachment of the retina and optic neuropathy. The development of a tumor inside the orbit can cause motility problems to the eye or even exophthalmos. Occlusion of the cilioretinal artery from metastatic tumor conglomerates can also lead to decreased vision or blindness.[78] In our literature review, the most common symptom was partial or complete loss of vision; pain was referred only in 9 cases and proptosis in 6 cases.

The diagnosis of an ocular malignancy can be accomplished with several methods. Fundus photography helps to cartograph the lesions and measure their sizes. Ultrasound can measure the dimensions of a tumor and also differentiate between primary and secondary lesions based on the unique sonographic characteristics.[79] Computed tomography (CT) can be utilized for the depiction of the eye and brain, while ocular computed tomography (OCT) creates cross-sectional images of the retina and can visualize the borders of the tumor as well as retinal disturbance.[80] Lastly, magnetic resonance imaging (MRI) can be utilized, especially in cases of inadequate fundoscopy (e.g., cataract) and positron emission tomography to locate the primary tumor source and multvisceral involvement.[81] In our literature review, CT was utilized in 24 cases, while MRI in 20 cases. Fluorescein angiography was also implemented in 10 cases to localize the lesion.

Biopsy of the tumor largely depends on the location of the lesion and can be accomplished either with fine needle biopsy or with surgical excision of the lesion.[82] In our review, we found that, in 43/70 cases, biopsy could not be obtained. This is probably due to the distinctive imaging characteristics that malignant tumors exhibit in the eye and the fact that, in most of these cases (30/43), there was concomitant metastasis to other organs.

The treatment of these patients is modulated according to their findings. In 59 patients, multivisceral metastasis was diagnosed. Treatment of the ocular lesion is usually by means of radiation therapy or excision of the tumor or enucleation. In our review, most cases received radiation therapy (60/70) with or without chemotherapy (6/70). Fifteen patients received only chemotherapy due to the extent of their disease or the chemosensitivity of the tumors (9/15 patients with GTN). Ten patients underwent surgery. Ten patients were operated primarily, while 1 patient was operated due to failure of the other treatments.

The prognosis of the ocular metastases is dismal. Jeddi et al.[83] reported that the mean life expectancy was 6.5 months. In our review, the mean survival time was 13.5 months. In 59 of our 70 retrieved cases, ocular metastasis was accompanied with metastasis to other organs too, especially lungs (32/70). This finding is anticipated because circulating tumor cells would reach the pulmonary circulation before reaching the eyes. Interestingly, we found only 9 CRs with brain metastases. The disease with the lowest mortality rate was ovarian cancer with a median survival of 16 months. The cases with the longest survival after the diagnosis of the ocular metastasis are patients suffering from choriocarcinoma. From our findings, it is obvious that patients with chemosensitive disease have longer survival intervals.

   Conclusion Top

Gynecological malignancies have a high burden in our society. Because our population is constantly growing older and life expectancy is rising, it is expected that gynecological cancer cases will increase. Modern treatment modalities have improved the survival rates of oncologic patients, and rare sites of distant metastasis have become more frequent. It is crucial that oncologists treating gynecologic cancer patients be vigilant during their follow-ups because eye metastasis foreshadows an ominous clinical course. To date, risk factors of ocular metastases have not been discovered. However, it should be noted that given their rarity, it is important to establish a prospective international registry, which will help determine prognostic factors of survival.

Strengths and limitations

Our study summarizes for the first-time tumor characteristics and survival rates of patients with ocular metastases from gynecological tumors. Direct implications for clinical practice are impossible due to the high possibility of selection bias; however, it should be noticed that ocular metastases, even as single site lesions, are associated with dismal prognosis, thus, indicating the need for aggressive patient management.

Author contributions

D.-E.V.: Guarantor, Data collection, drafting of the manuscript; N.T.: conception and design, data interpretation; DH critical revision of the manuscript; V.P.: acquisition and data, analysis and interpretation of data, statistical analysis; V.T.: Data collection and statistical analysis; A.P.L: data analysis, data interpretation; A.R.: conception and design, critical revision of the manuscript.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4]


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