Complex Ocular Adverse Events Following Oxaliplatin Treatment: A Case Report

Introduction

As a third-generation platinum-based chemotherapy drug, oxaliplatin plays a central role in the comprehensive treatment of malignant tumors. It inhibits tumor cell DNA replication and transcription through platinum-DNA complex formation and has been established as a first-line treatment for advanced colorectal cancer. It has also shown significant efficacy in the treatment of solid tumors, such as gastric cancer and ovarian cancer, providing patients with new treatment options [1]. However, similar to most chemotherapy drugs, oxaliplatin causes adverse reactions that involve multiple systems, including mainly neurotoxicity, such as peripheral neuropathy; hematological toxicity, such as neutropenia, thrombocytopenia, and anemia; and gastrointestinal symptoms, such as nausea, vomiting, and diarrhea [2]. These adverse effects not only reduce the quality of life of patients but also can affect the continuity and efficacy of chemotherapy.

Although ophthalmic toxicity is relatively rare in treatment with oxaliplatin, its clinical manifestations are often irreversible and highly disabling, including decreased vision, visual field defects, abnormal color vision, and in severe cases, permanent vision loss. Oxaliplatin can also induce acute neurotoxic mechanisms, such as laryngeal spasm and peripheral nerve sensory abnormalities [3]. In recent years, with the widespread use of oxaliplatin, the types and incidence of ophthalmic complications have been on the rise, gradually attracting the attention of clinicians and researchers [4]. At present, the mechanism of ophthalmic toxicity of oxaliplatin has not been fully elucidated. Most existing studies focus on hypotheses, such as oxidative stress and blood-retinal barrier disruption, but there is a lack of systematic evidence to support them [2]. This knowledge gap highlights the need for further exploration of its molecular mechanism.

This report describes the case of a 47-year-old woman with loss of vision in the right eye due to multiple iris cysts, anterior chamber inflammation, retinal detachment, and lens opacity while on a third round of treatment with oxaliplatin-based adjuvant chemotherapy following radical gastrectomy for adenocarcinoma of the esophagogastric junction.

Case Report

OPHTHALMIC EXAMINATION AND DIAGNOSIS:

Visual acuity in the right eye was 0.1 (uncorrected), and the left eye showed light perception only. Slit-lamp biomicroscopy revealed small avascular iris cysts at the pupil margin (Figure 1A).

Ultrasound biomicroscopy (UBM) detected low-echo masses behind the iris/ciliary body (Figure 1B). B-scan ultrasonography confirmed bilateral retinal detachment with subretinal fluid (Figure 1C). Optical coherence tomography (OCT) showed shallow foveal detachment with granular intraretinal hyperreflectivity (Figure 1D). Ultra-widefield fundus photography revealed blurred optic disc margins and tortuous retinal vessels (Figure 1E). Anterior segment photography showed an increased number of iris cysts with progression to milky-white cataract in both eyes (Figure 2).

As shown in Table 1, systemic workup, including orbital computed tomography and magnetic resonance imaging, excluded metastasis.

TREATMENT COURSE AND EVOLUTION:

In the initial management, oral prednisone acetate (anti-inflammatory) was prescribed, but the patient demonstrated poor adherence to the medication regimen, and there was no improvement in symptoms. The chemotherapy was adjusted to a regimen of oxaliplatin monotherapy (200 mg) and 5% glucose infusion (cycles 3–5). The patient underwent surgical intervention of the right eye with phacoemulsification on August 9, 2024. Interleukin (IL)-6 levels were elevated in the aqueous humor. In the left eye, combined phacoemulsification and iris cyst excision was performed on August 23, 2024. Pathology confirmed normal iris tissue (Table 1).

POSTOPERATIVE FOLLOW-UP:

The patient underwent phacoemulsification surgery in the right eye on August 9, 2024. Intraoperatively, the aqueous IL-6 level was elevated to 18.7 pg/mL (reference range: 0–5 pg/mL). Subsequently, on August 23, 2024, the patient had combined surgery on the left eye, which included excision of an iris cyst. Histopathological analysis of the excised tissue revealed normal findings.

There was transient improvement in vision (OD 0.5, OS 0.3); however, B-scan imaging revealed persistent retinal detachment. A residual macular schisis-like detachment with persistent granular hyperreflectivity was observed, when compared with Figure 1D from the early stage of chemotherapy. Ultra-widefield fundus photography demonstrated partial absorption of subretinal fluid, compared with the pre-surgical condition. However, the continued presence of blurred optic disc margins and tortuosity of the retinal vessels suggested that the retinal detachment had not fully resolved (Figure 3, Table 1).

LABORATORY AND IMAGING FOLLOW-UP:

Levels of the inflammatory marker serum IL-6 (reference range: 0–7 pg/mL) were increased during follow-up. Ocular imaging showed stable iris cysts with posterior capsular fibrosis. Persistent retinal detachment and OCT hyperreflectivity were also observed (Figure 4, Table 1).

Discussion

This study presents a comprehensive analysis of rare but severe ocular complications associated with oxaliplatin-based chemotherapy, including iris cysts, anterior chamber inflammation, exudative retinal detachment, and cataracts, in a 47-year-old patient with gastric cancer. The integration of clinical, imaging, and pathological data reveals multifactorial mechanisms underlying these complications, emphasizing the need for tailored surveillance and management strategies.

The iris cysts in this case likely originated from direct oxaliplatin toxicity to the iris pigment epithelium via platinum-DNA adduct formation, as supported by prior studies [5]. Concurrently, IL-6-mediated alterations in vascular permeability may have contributed to cyst expansion and recurrence [6]. UBM precisely localized the cysts behind the iris/ciliary body (Figure 1B), guiding surgical resection combined with cataract surgery in the left eye. Despite histopathology revealing normal tissue, suggesting a functional rather than neoplastic etiology, mechanical obstruction relief via surgery remained effective, underscoring the importance of anatomical imaging in guiding interventions.

Anterior chamber inflammation was driven by a drug-induced cytokine storm, with the peak aqueous humor IL-6 level of 156 pg/mL serving as critical evidence. Slit-lamp examination confirmed aqueous cells and flare, consistent with cytokine-mediated vascular leakage. Management required intensified anti-inflammatory treatment (eg, topical/systemic corticosteroids), but oral prednisone was unsuccessful owing to poor patient adherence to the medication regimen, highlighting challenges in controlling inflammation without adequate adherence.

Exudative retinal detachment resulted from a breakdown of the blood-retinal barrier, due to oxaliplatin-induced damage to retinal pigment epithelial cells, synergized by IL-6-mediated vascular leakage [6,7]. The patient’s comorbidities – hypertension and polycythemia vera – likely exacerbated vascular instability, compounding the exudative process [8]. Dynamic monitoring via B-scan ultrasonography and OCT demonstrated persistent subretinal fluid (Figures 1C, 1E, 3A), indicating ongoing barrier dysfunction. Treatment focused on controlling systemic inflammation by adjusting the chemotherapy regimen to oxaliplatin monotherapy, as surgical interventions, such as membrane peeling, were ineffective against the exudative etiology. This approach aligns with the principle of addressing inflammatory drivers rather than anatomical sequelae in drug-induced exudative retinal detachment.

The cataracts exhibited rapid progression, with milky lens opacity emerging after 3 chemotherapy cycles (Figure 2), likely due to oxidative damage from platinum accumulation in the lens [5,9]. Phacoemulsification, performed separately in both eyes in August 2024, temporarily improved vision (OD to 0.5, OS to 0.3) but was limited by postoperative posterior capsular fibrosis (Figure 4A) and persistent exudative retinal detachment. These outcomes suggest that cataract surgery should be deferred until inflammation is controlled, to optimize prognosis, as preoperative cytokine storms can increase the risk of fibrosis and recurrent detachment. This timing consideration is critical for patients with concurrent ocular inflammatory conditions.

The interplay between oxaliplatin toxicity and comorbidities, such as hypertension and polycythemia vera, in this case underscores the heightened vulnerability of patients with preexisting vascular instability to severe ocular complications. Mesquida et al (2010) described reversible retinal pigment epithelium dysfunction, such as visual field defects and electrophysiological abnormalities, in a colorectal cancer patient treated with oxaliplatin, suggesting that early retinal pigment epithelium injury can be partially reversible [1]. However, unlike the acute reversible vision loss of optic neuritis or vasospasm reported by Ah-Thiane et al (2021) [10], our patient’s persistent exudative retinal detachment and iris cysts indicated a chronic inflammatory process. Elevated aqueous humor IL-6 levels across all complications, including iris cysts, exudative retinal detachment, and cataract, further implicated systemic inflammation as a unifying pathogenic mechanism, driven by platinum-DNA adduct formation and cytokine dysregulation. IL-6, a key pro-inflammatory cytokine, is known to disrupt the blood-retinal barrier by increasing vascular permeability [6,7], thereby exacerbating fluid exudation and cyst expansion. These findings advocate for early multimodal ophthalmic screening, such as UBM, OCT, and cytokine profiling, in patients receiving oxaliplatin, particularly those with vascular risk factors, to detect toxicity before irreversible damage occurs.

Future research should explore molecular pathways linking platinum exposure to ocular inflammation, including proteomic analysis of aqueous humor and in vitro models of retinal pigment epithelium/iris pigment epithelium toxicity. Larger cohort studies are needed to validate risk stratification tools, such as IL-6 thresholds and cumulative dosing algorithms, and optimize treatment protocols. For instance, prophylactic anti-inflammatory agents or dose modifications may mitigate toxicity in high-risk patients, while surgical timing guidelines could improve outcomes for cataracts and exudative retinal detachment.

This case has limitations, including its single-patient design and lack of longitudinal cytokine profiling beyond IL-6, which restricts generalizability. Additionally, the inability to perform retinal pigment epithelium histopathology precludes definitive conclusions about the role of platinum in barrier dysfunction. However, the integration of multimodal imaging and aqueous humor biomarkers provides a novel framework for understanding platinum-induced ocular toxicity.

Conclusions

This case confirms that oxaliplatin-based chemotherapy can induce rare ocular toxicities, including iris cysts, exudative retinal detachment, and cataracts, in patients with gastric cancer. An elevated aqueous humor IL-6 level of 156 pg/mL suggested inflammation-driven angiogenesis as a key pathogenic mechanism in this case. Early multimodal ophthalmic screening (OCT/UBM) and multidisciplinary management (surgical intervention and chemotherapy adjustment) are critical for mitigating irreversible vision loss. These findings underscore the need for oncologists to prioritize ocular surveillance in platinum-treated patients by integrating imaging, biomarkers, such as IL-6, and pathological data into clinical protocols.