A Case Report of Intravitreal Aflibercept for Iris Metastasis from Small Cell Lung Carcinoma with Neovascular Glaucoma

Metastatic iris tumors from lung cancer are uncommon [1] and can be challenging to diagnose due to their diverse clinical presentations [2]. However, with advancements in biological technologies for lung cancer treatment, the life expectancy of patients with advanced-stage lung cancer is expected to increase [3]. Consequently, the incidence of metastatic iris tumors may rise, making accurate diagnosis increasingly important.

Metastatic iris tumors are frequently associated with neovascular glaucoma [4], necessitating effective management of intraocular pressure (IOP). However, the overall prognosis and life expectancy of patients must also be carefully considered.

Here, we present a case of a metastatic iris tumor originating from lung cancer, initially presenting with clinical features similar to those of granulomatous anterior uveitis. Anterior chamber cytology proved valuable for diagnosis. Conservative management of the associated neovascular glaucoma was achieved through an intravitreal aflibercept injection, approved for insurance coverage in Japan. This approach effectively alleviated the patient’s symptoms, providing relief during their end-of-life care.

A 65-year-old man was referred to our hospital, with suspected uveitis of the right eye. He had experienced right ocular pain and blurred vision 1 month prior to presentation and visited his local doctor. Four months earlier, he had been diagnosed with small cell lung cancer (SCLC) (cT4N3M1c) with right cerebellar metastasis and invasion of the trachea and mediastinum. The patient underwent chemotherapy with four cycles of carboplatin/etoposide, followed by secondary chemotherapy with amrubicin. His visual acuity was 0.1 OD (uncorrectable) and 0.4 (0.5 × S − 1.75 D A × 85°) OS. His IOP was 55 mm Hg (OD) and 11 mm Hg (OS), measured using a Goldmann applanation tonometer. A slit-lamp examination of the right eye revealed corneal stromal edema. The anterior chamber contained 3+ cells and neovascularization of the iris at the pupillary border. Numerous irregular grayish-white masses were present on the corneal surface and scattered in the anterior chamber as shown in Figure 1a. Grade 1.5 nuclear sclerosis was also observed. Gonioscopy showed a whitish irregular mass originating from the anterior iris surface and extending to the anterior part of the trabecular meshwork. The anterior segment of the left eye was normal. Fundus examination of both eyes was unremarkable, with normal discs and macula. The iris mass was presumed to be a metastasis from the SCLC, and neovascular glaucoma due to iris metastasis from the SCLC was suspected. Therapy was initiated with topical 0.005% latanoprost, 1.0% brinzolamide, 0.5% timolol maleate, and oral acetazolamide at a dose of 500 mg/day. Because of high IOP and pronounced nausea, intravenous administration of 200 mL of 20% hypertonic mannitol was required every 2–3 days, for a total of five administrations. Anterior chamber fluid cytology was performed 10 days after the initial visit to confirm the diagnosis. The pathological findings from Papanicolaou staining were consistent with the results of bronchoalveolar lavage cytology, leading to a diagnosis of iris metastasis from SCLC, as shown in Figure 2a and b. Despite therapy, IOP continued to be poorly controlled, and the patient continued to experience ocular pain. After obtaining informed consent, a single injection of 2 mg (0.05 mL of 40 mg/mL) aflibercept (Bayer Yakuhin, Ltd., Osaka, Japan) was administered intravitreally OD to treat the neovascular glaucoma 10 days after initial visit. Five days after the aflibercept injection, the iris tumor had decreased in size, iris neovascularization had decreased, and the IOP was measured at 18 mm Hg as shown in Figure 1b. Continued use of antiglaucoma medications was necessary to maintain the IOP within the normal range. However, intravenous infusion of hypertonic mannitol was no longer required, and ocular pain and nausea were relieved. One month after the first visit to our hospital, the patient was transferred to a palliative care facility. Three months later, the patient succumbed to multiorgan metastasis of SCLC.

This case demonstrates two key points: metastatic iris tumors can resemble the clinical presentation of granulomatous uveitis. However, the diagnosis was facilitated by anterior chamber aqueous humor cytology. The accompanying neovascular glaucoma was managed conservatively with intravitreal injections of aflibercept, which effectively alleviated ocular symptoms, contributing to a favorable prognosis for the patient’s quality of life.

Metastatic iris tumors are characterized by several clinical manifestations [1], including the presence of an iris mass, inflammation of the iris and ciliary body, anterior chamber hemorrhage due to neovascularization, and secondary glaucoma [4]. In this case, the patient presented with posterior corneal deposits containing pigment, inflammation of the iris and ciliary body, scattered white masses in the posterior cornea, mid-anterior chamber, anterior chamber angle, and iris rubeosis. Given the patient’s ongoing treatment for stage IV SCLC, the diagnosis of a metastatic iris tumor was readily possible. A definitive diagnosis through histological or cytological examination is essential to determine the appropriate course of treatment.

Postoperative anterior chamber hemorrhage occurs in approximately 34% of cases after histological examination [5], and there is a risk of tumor cell seeding during tissue collection. However, reports indicate that anterior chamber aqueous humor cytology can provide a definitive diagnosis [5]. This method is advantageous because it can be performed in an outpatient setting. In this case, despite cellular degeneration, the atypical cells resembled those observed in the bronchoalveolar lavage fluid cytology previously conducted in respiratory medicine, leading to the definitive diagnosis of a metastatic iris tumor.

The accompanying neovascular glaucoma was managed conservatively with intravitreal injections of aflibercept, considering the patient’s prognosis, and this approach effectively alleviated the symptoms. Treatment options for refractory glaucoma secondary to tumor invasion of the iris or neovascularization include irradiation, photocoagulation, ocular extraction, and intravitreal anti-VEGF injections [6]. Radiation therapy was considered an option in this case but was not chosen due to the patient’s wishes and the overall condition associated with stage IV small cell carcinoma. Other treatment options for IOP and pain control, such as retrobulbar alcohol or chlorpromazine with or without cyclophotocoagulation, were also considered. However, these procedures were challenging to perform at our hospital, and the patient chose not to pursue treatment at another facility. Anti-VEGF vitreous injections, such as bevacizumab, can locally expose tumors to high doses of the drug and effectively shrink tumors, regressing neovascularization and lowering IOP [7, 8]. Based on clinical trials [9, 10], intravitreal injection of aflibercept was approved for insurance coverage in Japan for the treatment of neovascular glaucoma in March 2020. Other anti-VEGF agents like bevacizumab and ranibizumab are not currently covered by insurance in Japan. While recent studies [11] have compared the efficacy of various anti-VEGF agents for neovascular glaucoma, this report focuses on treatments within the scope of insurance coverage. In future, if insurance coverage is expanded, distinguishing between the use of different anti-VEGF agents for neovascular glaucoma will likely become important. Although reports on aflibercept’s use in neovascular glaucoma caused by tumors are limited [12], this case demonstrated its efficacy in shrinking the tumor, regressing neovascular vessels, and lowering IOP.

The average life expectancy following the development of iris metastasis is approximately 12 months [6]. In this case, the patient died 4 months after the initial diagnosis, leaving the long-term efficacy of aflibercept for neovascular glaucoma uncertain. However, during this period, intravitreal injections of aflibercept effectively reduced IOP and alleviated symptoms such as nausea.

In summary, metastatic iris tumors resemble the clinical presentation of granulomatous uveitis; however, diagnosis is facilitated by anterior chamber aqueous humor cytology. In this case, associated neovascular glaucoma was effectively managed conservatively with intravitreal aflibercept injections, approved for insurance coverage in Japan, taking into account the prognosis of patients in the terminal phase of the disease.

With advances in medical science, the life expectancy of patients with cancer-bearing tumors is increasing, and the incidence of metastatic iris tumors is also expected to rise. Intravitreal anti-VEGF injections are useful for symptomatic treatment.

The authors adhered to the code of ethics of the Department of Ophthalmology at Nippon Medical School, Tokyo, Japan. This study protocol was reviewed, and the need for approval was waived by the Central Ethics Committee of Nippon Medical School. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images prior to their passing away.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Hitoshi Goto contributed to the conception and design of the study, served as the primary physician managing the patient case, acquired and interpreted clinical data, and drafted and revised the manuscript. Kirie Hirakata assisted in patient management, provided clinical insights, and critically reviewed the manuscript. Kenji Nakamoto supervised the clinical aspects of the case, offered expert guidance, and revised the manuscript for intellectual content. Fumiki Okamoto provided senior oversight and reviewed the manuscript for accuracy and coherence. Junko Hori contributed to the study design, provided senior clinical input, and approved the final version of the manuscript.

All data generated or analyzed during this study are included in this published article. Further inquiries can be directed to the corresponding author. The CARE Checklist has been completed by the authors for this case report and is attached as online supplementary material (https://doi.org/10.1159/000544159).