Abstract
Background
In the last decade cancer treatment has rapidly evolved, contributing to a significant improvement in survival rates due to different and novel treatment options. The development of targeted therapies has dramatically changed our way to approach this disease, allowing to selectively target specific pathways uniquely expressed by cancer cells and absent in normal ones. This new era has been characterized by the use of molecules like BRAF/MEK inhibitors or checkpoint Inhibitors. The term MEKAR (MEK-Inhibitor Associated Retinopathy) has been developed to describe the class effect dose/time dependent retinal adverse effects that are mainly characterized by the accumulation of subretinal fluid. The underlying mechanism of ocular side effects linked to checkpoint inhibitors is likely immune-mediated and has a prevalence of approximately 1%.
Objectives
Many hypotheses have been proposed to explain retinal toxicity related to the use of different targeted therapies, but the pathogenesis is still not well understood. The aim of my research is to better clarify the mechanisms contributing to retinal abnormalities, analyze for the first time the chorioretinal vascular network and the function of the retinal pigment epithelium cells.
Outcomes and Impact
In patients on treatment with BRAF/MEK or Pan-FGFR inhibitors, the analysis of chorioretinal vascular network did not show significant changes during the observation; on the contrary, early impairment of the retinal pigment epithelium cells function is present. The low incidence of ocular side effects related to the use of checkpoint inhibitors limits their assessment to large populations. Herein I described a rare instance of Acute Exudative Polymorphous Vitelliform Maculopathy (AEPVM) that occurred while receiving pembrolizumab treatment for metastatic melanoma. According to our findings, the expression of PD-L1 on RPE cells may contribute to ocular inflammation by suppressing immune responses. My research represents an important step forward in the direction of better understanding the retinal toxicities related to targeted cancer therapies. In this process, functional impairment of the retinal pigment epithelium cells plays a key role. Based on these findings, further studies are warranted to identify specific biomarkers at the level of the RPE cells that can favor a timely detection of those patients who have a greater risk of developing retinal toxicity.
In the last decade cancer treatment has rapidly evolved, contributing to a significant improvement in survival rates due to different and novel treatment options. The development of targeted therapies has dramatically changed our way to approach this disease, allowing to selectively target specific pathways uniquely expressed by cancer cells and absent in normal ones. This new era has been characterized by the use of molecules like BRAF/MEK inhibitors or checkpoint Inhibitors. The term MEKAR (MEK-Inhibitor Associated Retinopathy) has been developed to describe the class effect dose/time dependent retinal adverse effects that are mainly characterized by the accumulation of subretinal fluid. The underlying mechanism of ocular side effects linked to checkpoint inhibitors is likely immune-mediated and has a prevalence of approximately 1%.
Objectives
Many hypotheses have been proposed to explain retinal toxicity related to the use of different targeted therapies, but the pathogenesis is still not well understood. The aim of my research is to better clarify the mechanisms contributing to retinal abnormalities, analyze for the first time the chorioretinal vascular network and the function of the retinal pigment epithelium cells.
Outcomes and Impact
In patients on treatment with BRAF/MEK or Pan-FGFR inhibitors, the analysis of chorioretinal vascular network did not show significant changes during the observation; on the contrary, early impairment of the retinal pigment epithelium cells function is present. The low incidence of ocular side effects related to the use of checkpoint inhibitors limits their assessment to large populations. Herein I described a rare instance of Acute Exudative Polymorphous Vitelliform Maculopathy (AEPVM) that occurred while receiving pembrolizumab treatment for metastatic melanoma. According to our findings, the expression of PD-L1 on RPE cells may contribute to ocular inflammation by suppressing immune responses. My research represents an important step forward in the direction of better understanding the retinal toxicities related to targeted cancer therapies. In this process, functional impairment of the retinal pigment epithelium cells plays a key role. Based on these findings, further studies are warranted to identify specific biomarkers at the level of the RPE cells that can favor a timely detection of those patients who have a greater risk of developing retinal toxicity.
| Original language | English |
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| Award date | 4 Dec 2023 |
| Publication status | Published - 2023 |