 I'm Sravya Guinta, as Adam mentioned. I'm representing on intense pulse light therapy, which is being used as a novel treatment for refractory dry disease around the country. I became involved in this research while working with Dr. Joanne Shen, who's a clinical specialist at the Mayo Clinic Arizona. So I'm going to go over what intense pulse light therapy is, the possible mechanisms of action and retrospective clinic. Here's the topic. There's a need for better dry eye disease therapies, as we know. The may-go-may-glan dysfunction is the primary cause of evaporative dry eye disease and contributes to acute patient dry eye disease. It's also a major contributor to poor quality of life in these patients. The goal of may-go-may-glan therapy is to provide long-term improvements of symptoms for patients and to improve objective factors like may them quality, improve tear film stability, and decrease inflammation. While there's a variety of treatment options available for these patients, like topical cyclosporin, systemic doxycycline, and thermal pulsation, patients often don't experience complete or long-term resolution of their symptoms. So what is intense pulse light therapy, also known as IPL? It's adapted from the field of dermatology, where it's FDA approved for the use of to treat of chelanctatias, acne rosacea, acne vulgaris, unwanted hair, and even photo damaged skin. So this is a picture of the xenon flash lamb right here. And this is the device that's actually using high-intensity light source that's polychromatic and incoherent, with wavelengths in the range of the 500s to the 1200 nanometers. And with the intensity or energy level of eight to 20 joules per centimeter squared. It's an expensive treatment. It costs about $500 for treatment of both eyes. So the story of how IPL came to ophthalmology is interesting. Dr. Melinda Toyos is a comprehensive ophthalmologist in private practice in Memphis, Tennessee. And he was treating as a side business, some acne rosacea patients with IPL. The patients came back to him and said, well, my dry eye disease is actually improving. So he received a grant to test this further. He didn't find any significant results, but he did come up with the Toyos technique, which is described here in these pictures. So first, eye shield are applied to the patient's eyelids to protect the irises from the xenon flash lamb. Then ultrasound gel is applied to these areas, the upper cheeks and the temporal areas. And 30 flashes of light are applied in those areas where you see the red dots. Then the IPL eye shields are removed and the patient undergoes forceful maybel bean gland expression of the upper and lower eyelids to help secrete those toothpaste-like thick secretions that are clogging up those maybel bean glands. It's pretty painful at this point. The IPL itself only feels like a mild pinch every time the pulse is applied. Patients usually receive one to four treatments that are about one month apart. And then afterwards they can receive maintenance treatments about every month or so. Dr. Toyos has trained several ophthalmologists around the country. Now there's over 40 centers that perform IPL nationally, but there aren't any in Utah last time I checked earlier this week. So the mechanism of action of IPL is not completely understood yet, but we have some ideas based on in vitro chromophore research and in vivo dermatology and ENT research. So we know that the skin has two primary chromophores, melanin and hemoglobin. The energy absorbed by melanin decreases at the wavelength of light increases, whereas oxyhemoglobin absorbs light at a peak wavelength of 578 nanometers, which is the wavelength of yellow light. So when yellow light is applied to the skin, it's able to pass through the upper layers of the skin without being significantly absorbed by the melanin. It reaches the oxyhemoglobin in the blood vessels. The oxyhemoglobin converts that light energy into heat energy, which then coagulates the vessels. In a situation like acne rosacea, the more leaky blood vessels would be coagulated and this would lead to less inflammation and inflammatory markers reaching the eyelids in dry places. They'll work best with patients who have telangiectasis. There's also been some research in dermatology in in vivo acne vulgaris, showing that there is some upregulation of these inflammatory mediators. So TGF beta specifically is upregulated after IPL treatments. TNF alpha is downregulated, but this isn't necessarily applied to acne rosacea. Of note, application of heat as like thermal pulsation is not a mechanism of action of IPL. This is because research has shown that IPL, post-IPL, the skin temperature only increases about one degree Celsius. So next I'd like to talk about the retrospective study that was done at Mayo Clinic, in which we performed the toryos technique and we found that it does improve dry symptoms and mycobing gland function in refractory dry eye patients. This is an analysis of our preliminary data. So in this study, we found 36 patients who had complete data pre and post IPL to be involved, to be included in the study. Patient selection was left rather broad. Patients did not necessarily have to have ocular rosacea. We figured if patients have had refractory dry eye disease for a while, then they most likely have some mycobing gland dysfunction anyway. So this treatment may help them. So patient selection included increasing speed two scores and they would have had to fail all other therapies subjectively. So speed two is a symptom survey of dry eye disease severity that patients can fill out. It's a validated survey, just like an ocular surface disease index. And as that number increases, so from zero to 28, as higher numbers of speed two indicate more severe dry eye disease. Patients also had to have Fitzpatrick skin types one through four. Fitzpatrick skin type ranges from one to six and five and six were excluded because they have higher melanin levels. They would have been at risk for higher photo damage. Patients were treated with the Toyos technique of IPL and mycobing gland expression. And then before each treatment with IPL, patients underwent speed two score symptom survey and then they had a foot length exam and mycobing gland evaluation. So mycobing gland evaluation is counting the number of lower eyelid mycobing glands that yield liquid secretions. Those are the normal healthy secretions when gentle force, gentle continuous pressure is applied. And then our primary measures were to look at how many of those glands were expressing. So mycobing gland evaluation and speed two score. There's a minimum of six months of follow up after the first IPL, mycobing gland expression therapy. Our results showed that there was a significant decrease in speed two scores with this therapy and speed two scores improved in eight, nine percent of patients. However, a small portion did have no change or an increase in speed two. So worsening symptoms. MGE or the number of glands that yielding those liquid secretions in at least one eye was improved in 78% of patients. 42% of patients had improvement in both eyes. So in summary, a motor road of patients had an improvement in mycobing gland expression and speed two. However, there are many limitations to the study as you can probably notice. The major confounding factor is that there was mycobing gland expression also combined with IPL therapy. So we didn't test IPL on its own. We tested the Toyos technique which is used around the country. Patients may have continued the use of drops. We didn't ask them to discontinue those at home. So preservative free drops. We also didn't select for a specific etiology or dry disease among patients. So there may have been some patients with sugar and disease or graft versus host disease and we plan to go back and exclude those patients from our study. Patients may also have had other causes of aqueous division dry eye like lack of thalmos. So those patients wouldn't have improved if we did IPL on them. The minority of patients who didn't improve may have also been part of the older population. We did have an older population in our study. Median age was 65 years. They may have had end stage gland atrophy. This would have been helpful to evaluate this with maybography to see if that was actually the case. So you may have missed the therapeutic window of these patients. So while I'm talking about the limitations of our study, I also wanted to mention the controversy surrounding IPL. There are believers and there are non-believers and the mechanism action IPL is not proven. So we're still in the process of figuring that out. Often IPL therapy is confounded with adjunctive therapies like the lid massages and expression and also sometimes drops as well in some places. There's no treatment of the lid margin directly so people wonder well how are we actually affecting the maybobing glands. Also another point of contention is that it's not a cure. If you take acne rosacea as an example, treating the telangiectasis themselves is not treating the cause of the disease or treating an outcome of the disease. The cause of acne rosacea is not necessarily known but it's a dysfunction in the innate immune system. It's also an expensive therapy that's not FDA approved. But in support of the efficacy of IPL alone, Jennifer Craig who's an opometrist in New Zealand published a prospective double mast, placebo controlled paired eye study and she found that in her 28 patients there was an improvement in lipid layer grade and tear breakup time and also an improvement in speed score post IPL. She tested IPL on its own without the maybobing gland expression. So this is published this year and two other studies that are retrospective also published this year using the Toyos technique are by Dr. Toyos and Dr. Gupta at the Duke Eye Center and they also found that there was an improvement in made in quality and tear breakup time and the symptoms scoring the majority of patients. So with that, I'd like to thank you for the opportunity to be at the Moran to present to you all today, thank you. The problem is when you get a therapy like this that's touted with retrospective studies without perspective studies, with training sessions where you have to go out and get approved by the person who invents this therapy, it just screams for prospective mastism. I'm glad you did show one. Yeah. Showed that it had something because when you're not sure what the mechanism is to say, well, the lower the treatment of the study, the reason why you don't see it shows that when you're not doing, pushing on the secretions themselves just doing the therapy, which you want to do it possible. So we desperately need no good treatments for my bulging gland. The other thing that has always come up. It is. The reason why we don't treat the upper lids directly is that there has been a case report published that the iris was zapped during one of these treatments. Yeah. That's why you keep those eye shields on. You're like crazy, taking the spurs to everywhere. Yeah. That's good. Thank you. I agree that sometimes when patients do invest that much money, their perception of their improvement also changes sometimes. They invest in that much time and money. Yeah, they don't really feel the pressure. And there is proof that my bulging gland expression in previous studies does alone improve. Thank you. Thank you.