Role of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Uveal Metastases Volume 52- Issue 5

Georges Sukkarieh¹*, Tarek Rustom¹, Amine Al Soueidy¹, Hampig Raphael Kourie² and Joelle Antoun¹

• ¹Ophthalmology Department, Hȏtel-Dieu de France Hospital, Faculty of Medecine, Saint Joseph University, Lebanon
• ²Hematology-Oncology Department, Hȏtel-Dieu de France Hospital, Faculty of Medicine, Saint Joseph University of Beirut, Lebanon

Received: August 17, 2023;   Published: September 11, 2023

*Corresponding author: Georges Sukkarieh, Ophthalmology Department, Hȏtel-Dieu de France Hospital, Faculty of Medecine, Saint Joseph University, Beirut, Lebanon

DOI: 10.26717/BJSTR.2023.52.008310

Abstract PDF

Introduction: Anti-vascular endothelial growth factor agents (Anti-VEGF) have been recently used, locally and systemically, in the treatment of uveal metastases. The aim of this review is to summarize the available data concerning response of uveal metastases to intraocular and/or systemic anti-VEGF agents.

Methods: An exhaustive PubMed database search for articles describing the treatment of iris or choroidal metastasis (CM) with anti-VEGF agents was done.

Results: In total, 48 case reports and case series describing anti-VEGF use in iris and choroidal metastases (CM) were collected. Thirty-two out of 43 cases of CM treated by intravitreal anti-VEGF injections had a positive response. Four out of 6 cases of CM secondary to non-small cell lung carcinoma responded well to systemic anti-VEGF. Iris metastases regressed in the 12 reported cases of iris metastases treated by intraocular anti-VEGF. No reported cases were found concerning the treatment of iris metastases with systemic anti-VEGF molecules.

Conclusion: Anti-VEGF intraocular injections seem to be a valid alternative for the palliative management of patients with iris or choroidal metastases by promptly reducing pain, improving visual acuity and reducing tumor size thus ameliorating the patient’s quality of life.

Keywords: Choroidal Metastases; Intravitreal Anti-VEGF Injection; Iris Metastases; Systemic Anti-VEGF; Uveal Metastases

Abbreviations: BD: Behçet Disease; ESR: Erythrocyte Sedimentation Rate; CRP: C-Reactive Protein; HSV: Herpes Simplex Virus; JAK: Janus Kinase; ACR: American Criteria of Rheumatology; MHC: Major Histocompatibility Complex; TNF: Tumor Necrosis Factor; eNOS: Endothelial Nitric Oxide Synthetase; STAT: Signal Transducer and Activator of Transcription; PBMCS: Peripheral Blood Mononuclear Cells

Anti-vascular endothelial growth factor agents (Anti-VEGF) have been used, locally and systemically, in the treatment of uveal metastases. The objective of this article is to review the available data concerning the intraocular and/or systemic anti-VEGF agents treatment of uveal metastases.

A database search was performed on PubMed, using the keywords “choroidal metastasis”, “choroidal metastases”, “iris metastasis” and “iris metastases” in combination with the terms: “bevacizumab”, “ranibizumab”, “aflibercept” and “intravitreal injection”. All published articles up until 30 March 2021, describing the treatment of iris or choroidal metastases (CM) were included. In total, 48 case reports and/or case series were collected: 27 articles of anti-VEGF IVI for CM, 9 articles of systemic anti-VEGF use for CM and 12 articles of anti-VEGF IVI for iris metastases (IM). The main findings of the 48 articles are presented in the Table 1. The following text summarizes main features of anti-VEGF IVI role in treating ocular metastases.

Intravitreal Anti-VEGF for Choroidal Metastases

Anti VEGF-IVI in Lung Cancer CM: 17 cases of CM secondary to lung cancer were found (12 of non-small cell lung carcinoma (NSCLC) and 5 of small cell lung carcinoma (SCLC)). Among patients with CM from NSCLC, visual acuity improved in 8 cases, decreased in 1 case, was not reported in 2 cases, and in 1 case of bilateral CM visual acuity remained stable in 1 eye and decreased in the other. Concerning SCLC, visual acuity improved in 4 cases and worsened in 1 case. Among all patients with lung carcinoma that benefited from anti-VEGF IVI, improvement of visual acuity was reported as early as 1-2 weeks after IVI injection in 3 cases [1-3].

Anti-VEGF IVI in Breast Cancer: In total 13 cases of CM secondary to breast cancer were treated with IVIs. Visual acuity improved in 8 cases, deteriorated in 4, and one case with bilateral disease had improvement in an eye and deterioration in the other. Visual acuity improved as early as 3 weeks in some cases [4-6].

Anti-VEGF IVI in Other Tumors: 5 cases presenting with colorectal carcinoma were treated by anti-VEGF injections. Two cases presented improvement, while two cases presented a deterioration. One patient with bilateral CM presented a regression of tumor with stable visual acuity in an eye, and progression of disease in the other eye [7]. Details of all reported cases of CM treated by Anti-VEGF can be found in Table 1.

Table 1: Studies using intravitreal anti-VEGF for the treatment of choroidal metastases.

Note: BCVA: Best corrected visual acuity; CF: Counting fingers; CM: Choroidal metastasis; CT: chemotherapy; EBRT: External beam radiotherapy; ER: Estrogen receptor; FOLFIRI: Folinic acid, Fluorouracil, Irinotecan FOLOFOX: Folinic acid, Fluorouracil,Oxaliplatin; Gy: Gray; HER 2: Human epidermal growth factor receptor 2; I-131: Iodine-131; ICG: Indocyanin green; IVI: Intravitreal injection; KRAS: Kirsten rat sarcoma viral oncogene homolog; LE: Left eye; NR: not reported; NSCLC: Non-small cell lung cancer; OCT: Optical coherence tomography; PDT: Photodynamic Therapy; PR: Progesterone receptor; RE: Right eye; Ru-106: Ruthenium -106; SRF: Subretinal fluid; TTT: Transpupillary thermotherapy; VEGF: Vascular endothelial growth factor.

Systemic Anti-VEGF for Choroidal Metastases

Systemic anti-VEGF treatment of choroidal metastasis was reported 9 times (Table 2). No cases of iris metastases treated by systemic Anti-VEGF agents were found. Improvement of VA was reported in 4 cases and stability of VA at 20/20 in 1 case. No response was found in 1 case, and response was not reported in 3 cases. The positive response to systemic anti-VEGF remained stable for a follow-up of 18 weeks to 20 months [8-11].

Table 2: Studies using systemic bevacizumab for the treatment of choroidal metastases.

Note: 5 FU: 5-Fluorouracil; ALK: Anaplastic lymphoma kinase; AUC: Area under the curve ; CM: Choroidal metastasis; EGFR: Epidermal growth factor receptor; HM: Hand motion; IVI: Intravitreal injection; KRAS: Kirsten rat sarcoma viral oncogene homolog; NR: Not reported; SRF: Subretinal fluid; VA: Visual acuity.

Intravitreal Anti-VEGF for Iris Metastases

12 reported cases of iris metastasis treated by intraocular injections of anti-VEGF agents were found. All cases were unilateral except one case reported by Zhou et al. which was bilateral [12]. Anti-VEGF injections were given for secondary glaucoma with pain and reduced vision in 10 cases, reduced vision with no secondary glaucoma in 1 case [13] and for an asymptomatic iris metastasis in 1 case [14]. Cases with secondary glaucoma showed a decrease in IOP, pain and iris neovessels. Visual acuity improved in 6 cases, worsened in 1 case and was not reported in 5 cases.

Intravitreal Anti-VEGF for Choroidal Metastases

Intravitreal Anti-VEGF agents are effective because of their antiangiogenic effect, knowing that metastases rely on VEGF to develop their own blood supply [15,16]. This review shows that anti-VEGF IVI appear to be effective in treating choroidal metastasis since regression of choroidal metastases was reported in 32 of the 43 cases. Concomitant chemotherapy was used in 28 out of the 42 cases reported, that can overestimate the true response to the anti-VEGF injections but the fast recovery of visual acuity can be attributed to the effect of anti-VEGF.

Systemic Anti-VEGF for Choroidal Metastases

Response to systemic bevacizumab is probably due to its antiangiogenic effects since intravenous administration delivers the drug directly to the highly vascularized choroid. However, firm conclusions cannot be drawn because of the limited reported cases, where, moreover, multiple other systemic and/or local therapies were used.

Intravitreal Anti-VEGF for Iris Metastases

On our search of literature 12 reported cases of iris metastasis treated by intraocular injections of anti-VEGF agents were found and are detailed in Table 3. Iris metastases are markers of poor prognosis with a life expectancy of 10 months [17,18]. Hence, the main goal of the treatment is the improvement of the quality of life [17]. Many therapeutic options have been proposed for IM with multiple side effects and/or complications [17,18]. Taking into account all these considerations and since intravitreal anti-VEGF injections were able to show improvement in all 12 reported cases, anti-VEGF IVI seems to be a valid option for the treatment of iris metastasis. Intravitreal injection seems more adequate than intracameral injections because of the longer half-life of the molecules in the vitreous [19-62].

Table 3: Studies using intravitreal anti-VEGF injections for the treatment of iris metastases.

Note: CT: Chemotherapy; IOP: Intraocular pressure; VA: Visual acuity; IVI: Intravitreal injection; LE: Left eye; LP: Light perception; 5-FU: 5-Fluorouracil; NR: not reported; INV: Iris neovessels; RE: Right eye; SBRT: Stereotactic external-beam radiation therapy.

Limitations

First limitation of this review is that all acquired data are based on case reports. The second limitation is that cases that showed response to Anti-VEGF agents are more likely to be published.

Anti-VEGF intraocular injections seem to be a valid alternative for the palliative management of patients with iris or choroidal metastases by promptly reducing pain, improving visual acuity and reducing tumor size thus ameliorating the patient’s quality of life.

None.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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