Choroidal and Choriocapillaris Morphology in Pan-FGFR Inhibitor-Associated Retinopathy: A Case Report.

Emerging anticancer agents such as the pan-FGFR Inhibitor have achieved remarkable improvements in the survival of patients with metastatic malignancies. Nevertheless they are still associated with specific ophthalmic toxicities. Understanding their pathophysiology can lead us to better clinical practice of life-threatening and vision-threatening circumstances. To investigate choroidal alterations as a potential pathophysiological mechanism of a serous detachment in bilateral pan-FGFR Inhibitor-Associated Retinopathy (FGFRAR), the morphology of the choroid and choriocapillaris were assessed. The choroidal thickness (ChT) and choriocapillaris flow void were measured by macular optical coherence tomography (OCT) and angiography (OCT-A), respectively. Data were collected at the baseline, then at one-month and two-months follow-ups after starting erdafitinib, in a single case of pulmonary angiosarcoma. Choroidal and choriocapillaris morphology showed stable ChT and choriocapillaris flow void at FGFRAR onset and relapse. To the best of our knowledge, this is the first analyzed case reported with flow-void OCT-angiography. Considering these results, FGFRAR in this patient does not seem to match the pachychoroid spectrum disorder definition; rather, an intracellular mechanism based on intracellular transduction pathways may be at work.

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report.

BACKGROUND: The use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab. CASE PRESENTATION: A 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted. CONCLUSIONS: The development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.

Choriocapillaris Assessment In Patients Under Mek-Inhibitor Therapy For Cutaneous Melanoma: An Optical Coherence Tomography Angiography Study.

PURPOSE: The present study investigates by optical coherence tomography angiography (OCTA) the retinal capillary plexus and choriocapillaris flow voids and their possible correlation with MEKAR. METHODS: 34 eyes of 17 patients (61.5 years [30.4-77.4]) with stage IV cutaneous melanoma were included prospectively. All patients showed disease progression under treatment with Nivolumab/Ipilimumab and were subsequently treated with the MEK-inhibitor Trametinib 2 mg once daily. At the start and every 6 weeks during follow-up of 4 months, patients underwent a complete ophthalmologic exam, OCTA and when needed fluorescein angiography. RESULTS: Statistical analysis was performed on 17 eyes of 9 patients. Eight patients were excluded due to missing OCTA images or due to drop-out because of decease or change of treatment. Comparing vessel area density (P = .625 and 0.681, respectively), vessel skeleton density (P = .996 and 0.766, respectively) of the superficial and deep capillary plexus, flow void number and total flow void area (mm2 and %) (P = .495; 0.197 and 0.298, respectively) of choriocapillaris slab, before and after treatment, revealed no significant difference. The evolution of choriocapillaris flow void parameter did not significantly differ in patients, who developed MEKAR compared to patients who did not. CONCLUSION: In patients receiving MEK-inhibitor with and without MEKAR, no significant different characteristics of the retinal capillary plexus and choriocapillaris were found. These data suggest that the development of MEKAR, has no correlation with vascular alteration.

Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy.

ABSTRACT: Immune checkpoint inhibition has improved the clinical outcomes for numerous patients with cancer. However, the downside is a whole new spectrum of immune-related adverse events. We report a 68-year-old man with a history of nonsmall cell lung cancer presenting with a spontaneous corneal perforation in the right eye after 22 cycles of pembrolizumab. In addition, a chronic central nonhealing epithelial defect developed after performing a penetrating keratoplasty. Treatment with autologous serum drops resulted in complete healing of the corneal ulcer, where other conventional therapies had no effect. One month after reinitiating pembrolizumab therapy, our patient presented again with a corneal perforation in the fellow eye. This case describes relapsing sterile ulcerations associated with pembrolizumab use and presents an unexpected cure.

Breast Cancer Metastasis Presenting as Conjunctival Chemosis.

A 72-year-old woman presented with a painful right eye. A few weeks before, she had noticed a red, swollen area in the conjunctiva of the same eye. On slit lamp examination, it appeared as chemosis and vascular injection; artificial tears were prescribed. A month later, a firm mass developed on the superotemporal orbital rim, in the area of the lacrimal gland. A CT scan revealed infiltrative structures in both the left and right orbit, with contrast staining in the right lacrimal gland and near the left optic nerve. A biopsy was taken of the conjunctival swelling as well as of the lacrimal gland. Both tissues showed infiltration with lobular breast carcinoma metastases.