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Smoking and Increased risk of PVR: Is Increased TNF-alpha a Key Causative Factor?

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One presentation that I particularly enjoyed during ASRS was that of Dr. Ajay Kuriyan of Wills Eye Hospital/Mid Atlantic Retina. He reported on the association between proliferative vitreoretinopathy (PVR) and smoking. Previous authors have investigated this relationship, which is what inspired Dr. Kuriyan to utilize a mouse model of PVR that he developed to study this. He found that if retinal pigment epithelium (RPE) cells were exposed to smoke prior to injection in the mouse eyes, this led to more severe PVR formation. On histologic examination of the sections of the mouse eyes, there was noted to be more significant fibrosis in the mice that had the smoke-exposed RPE injections compared to the non-smoke exposed RPE injections.

Other studies of the effects of smoking have revealed that TNF-α is upregulated in the lung tissues of smokers. Dr. Kuriyan found RPE cells that are exposed to smoke results in TNF-α upregulation as well. Furthermore, inhibiting TNF-α in the RPE cells reduces smoking-induced changes associated with PVR formation, including the levels of cytokines and transcription factors associated with scarring. TNF-α has been found to be elevated in all patients with PVR, regardless of smoking status, so inhibiting this inflammatory cytokine could have broad benefits to many other patients as well. 

Even though it is not known if smoking cessation has any impact on future PVR formation, Dr. Kuriyan advises his patients to discontinue smoking due to the numerous other health benefits that it may confer. The psychosocial distress and functional impairment caused by recurrent retinal detachment could serve as a motivating factor for these patients to make this positive lifestyle change.

In order to advance his studies from the mouse model to human studies, Dr. Kuriyan plans to study TNF-α levels in smokers versus non-smokers by taking samples during vitrectomy. There are several FDA-approved biologic medications that inhibit TNF-α for uveitis and other rheumatologic conditions. Dr. Kuriyan hopes that by using TNF-α inhibitors to reduce PVR formation in the mouse model, this may set the stage to try this therapy in humans. 

As PVR is the number one cause of failed retinal detachment surgery, this represents a very large unmet need in retina care. Other studies have investigated the role of intravitreal methotrexate to prevent PVR formation, with early promising results. The more tools we have at our disposal, the better we will be able to serve our patients by reducing the incidence of recurrent retinal detachment due to PVR.

Dr. Hussain reports consulting fees from Alimera Sciences.

Illustration Collage by April Brust / Gettyimages

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