We recently spoke with Andrea Lora Kossler, MD, FACS, from the Byers Eye Institute at Stanford University about results from the study “Effect of Teprotumumab on Ocular Surface Disease in Active Thyroid Eye Disease,” which she and colleagues presented at the American Society or Ophthalmic Plastic & Reconstructive Surgery Annual Fall Scientific Symposium.


 

PW: Why is it important to study the effect of teprotumumab on ocular surface disease in active thyroid eye disease?
LK: Thyroid eye disease (TED) is an autoimmune inflammatory disorder that can have a variety of visual sequelae and a significant impact on patients’ quality of life and daily activity. Teprotumumab was recently approved by the FDA for the treatment of TED. Many studies have shown that it is effective for treating patients with active, moderate to severe TED. But patients with TED suffer from a variety of ocular sequelae, as I mentioned, and we wanted to take a deeper dive into to seeing how teprotumumab may affect the ocular surface and ocular surface disease in these patients. About 65% of patients with TED, complain of ocular surface symptoms and have dry eye disease or dry eye disease symptoms. So, we wanted to see if teprotumumab can have a positive impact on treating ocular surface disease and improving the symptoms for these patients.

 

What did you and your colleagues set out to determine with this study, and how was the study conducted?
The purpose of the study was to investigate the effect of teprotumumab on both qualitative and quantitative measures of ocular surface disease in patients who also had TED. TED is an autoimmune inflammatory condition, and dry eye disease, or ocular surface disease, is also an inflammatory condition. We wanted to see if treating the original cause of the ocular surface inflammation in patients with TED would have a positive impact on their qualitative and quantitative measures of this disease.

We had 16 patients who were treated with teprotumumab. At baseline, we gathered a variety of qualitative and quantitative measures. We gave every patient a quality-of-life questionnaire that was specifically related to their vision function. We also gave every patient a speed questionnaire that is basically a measure of patients’ frequency and the severity of their dry eye disease. We also did baseline measurements of their tear volume through a Schirmer’s test.

We also conducted meibography to determine meibomian gland dropout rate, and also assessed clinical exams for things like chemosis, and conjunctival injection. We evaluated participants at baseline and again after 24 weeks, following teprotumumab therapy, which is eight treatments every 3 weeks. What are your most important findings?
It’s important to note that this was a small study, but of the 16 patients we evaluated (mean age, 52; 13 females, there was a significant improvement in patients’ quality of life related to their visual function; the P value for that was 0.00018, a very significant improvement in the patient’s estimation of their vision functioning quality of life. We also found a significant improvement in their speed scores, which means that patients were experiencing a significant improvement in the frequency and severity of their dry eyes.

For latest news and updates

We also found that conjunctival injection, chemosis, and other ocular surface measures on clinical examination resolved, or improved in all patients. We also found improvements in Schirmer test and meibography evaluation results; although Shirmer tear volumes and meibomian glad dropout rates were not significant when we evaluated them objectively, I think there’s still significant importance in the amount of improvement that our patients experienced. I think this value will become significant with a higher number of patients. At baseline, the Schirmer tear score was 17 millimeters, and after 24 weeks, it increased to 20.14 millimeters. What I think is more important is that when we looked at patients who had a baseline abnormally low tear volume of less than 10 millimeters at five minutes, their Schirmer tear value volumes almost doubled at 24 weeks. Going from a Schirmer tear volume of 8 millimeters to 16 millimeters can mean significant relief of dry eye symptoms for these patients.

When we looked at meibography, we found an improvement in the grade of meibomian gland loss in about 35% of our patients and while. I think for those 35 patients to see structural improvement in meibomian gland dropout rate is very clinically significant for our patients. Patients’ meibomian gland dropout rate decreased from 46% at baseline to 35% at 24 weeks overall, and that was close to significant and very clinically meaningful for our patients.

So teprotumumab did improve both qualitative and quantitative measures of ocular surface disease, as well as visual functioning-related, quality-of-life measures at week 24 compared with baseline. We need to study this further

 

Do you have plans to confirm your findings in a larger group of patients and/or with longer-term outcomes?
We were so excited about these results that we decided to report them earlier on in our study. We are still actively treating and enrolling patients with TED, the majority of whom also have ocular surface symptoms or dry eye disease.

Dr. Ray Douglas and his team at Cedars–Sinai Medical Center evaluated this and presented some similar findings regarding Schirmer tear strips and volumes increasing with teprotumumab treatment. We’ve talked about teaming up together; I’m always happy to collaborate with others when it comes to finding new answers and new treatments for our patients with TED. So, we are looking at this further, I think others are looking at this further, and we also have other projects related to ocular surface disease and TED. We hope to have more data available soon.