Disclaimer: Medical information is not medical advice—read our disclaimer.
What is ocular graft-vs-host disease (GVHD)?
GVHD occurs in people who have received a stem cell transplant (SCT) and affects about 50-100K people per year in the US. 50-80% of people receiving SCT will go on to develop GVHD.
Most commonly SCT is performed for malignant diseases such as leukemia or lymphoma. There are also less common nonmalignant indications for SCT such as myelodysplastic syndrome and aplastic anemia. Dr. Sunshine then gives a brief overview of hematopoietic SCT and the pathophysiology of GVHD.
The goal of SCT is to elicit an immune response of donor cells against the malignant cells, referred to as a graft-vs-tumor response (GVT); GVHD occurs when there is an overactivation and immunologic attack of the recipient tissues by donor cells.
GVHD also has both acute and chronic forms and affects multiple body systems. Acute GVHD occurs in the first 100 days following SCT and has ocular involvement less commonly. Chronic GVHD on the other hand occurs greater than 100 days following SCT and is more likely to have ocular involvement.
Ocular GVHD (oGVHD) is one of the most impactful effects of GVHD on patient quality of life and will affect 40-60% of patients post SCT. It can be thought of as a severe dry eye disease, manifesting similar signs and symptoms such as infection, pain and ultimately carries risk for corneal perforation. It is a panocular surface disease with dysfunction of the tear film, lacrimal gland, epithelium, conjunctiva, meibomian glands and corneal nerves.
How do we diagnose ocular GVHD?
Dr. Sunshine describes the current standards for diagnosis of oGVHD. The gold standard for diagnostic criteria comes from the International Chronic oGVHD Consensus Group. Diagnosis is made by assigning a score in four categories:
- Corneal staining
- Conjunctival injection
- Schirmer’s test
- Ocular surface disease (OSD) index score
Each category is scored by severity and combined for a total score to determine severity. Systemic GVHD is also factored into diagnosis.
Another diagnosis framework is available from the National Institute of Health. This is a more simplified version that can potentially be performed by non-ophthalmologists.
Another factor that should be considered which is not present in either diagnosis framework but is a good indicator of oGVHD is conjunctival fibrosis.
How do we treat ocular GVHD?
Dr. Sunshine continues to discuss treatment following her discussion of diagnosis. She discusses four pillars of treatment:
- Replace moisture
- Treat meibomian gland dysfunction
- Prevent desiccation
- Control inflammation
She discusses the importance of starting treatment in these areas simultaneously, unlike traditional dry eye disease where therapies may be administered in succession stating, “treat aggressively and early.”
What are the gaps in our knowledge?
The first topic that Dr. Sunshine discusses is the gap in diagnosis, i.e. are we diagnosing early enough? The current recommendation is to use the NIH simplified diagnostic tool and to start at 6+ months. She goes on to describe her experience, which is that waiting until a patient is symptomatic is often too late to treat appropriately.
She then discusses a proposal from the 2020 NIH Chronic GVHD Consensus Project which suggests a baseline eye exam pre-transplant and/or three months post-transplant due to the irreversible nature of the ocular changes and the fact that once symptoms are present it may be too late to intervene effectively.
Another question Dr. Sunshine poses, is if it is possible to use biomarkers to diagnose. She discusses the possibility of using tears, imaging or both to diagnose. Dr. Sunshine is currently doing a study at the University of Maryland to determine whether this is possible.
What's next?
Dr. Sunshine discusses potential future treatment options. The first she discusses is the Janus kinase (JAK) inflammation pathway, citing JAK inhibitors as a potential way to decrease cytokine based inflammation in patients with oGVHD. She cites efficacy in a pilot study in four patients that she performed at the University of Maryland.
She then lays out her current research approach, the goal of which is to better understand the mechanisms of oGVHD in an effort to formulate better targeted treatments. Dr. Sunshine uses both mouse models and an ocular biobank to study the disease.
The webinar concludes with a detailed discussion based on audience questions.
Key takeaways include:
- What is ocular graft-vs-host disease (GVHD)?
- How do we diagnose ocular GVHD?
- How do we treat ocular GVHD?
- What are the gaps in our knowledge?
- What is next?
- Q&A
Eversight's free webinars are a great way for you to connect, learn and train digitally with leading ophthalmologists and researchers from around the world. We invite you to RSVP for scheduled webinars and browse our recording library.
Have an idea for a future topic? Interested in receiving timely and relevant information from Eversight? We'd love to hear from you!
About the author
Michael Szkarlat
Partner Development Director
Email | LinkedIn
Michael has been with Eversight since 2016 and has recently worked to develop Eversight's educational wet lab programs for EK surgery and a standardized protocol for DALK practice in a wet lab setting. His eye banking experience is rooted in the preparation of corneal grafts and spent nearly five years as Eversight’s Medical Director designee in charge of training clinical team members to prepare corneal tissue for DMEK and DSAEK surgery. In his time at Eversight, Michael has presented at scientific conferences, been involved in clinical research and developed innovations in tissue processing. He was named an IAPB Eye Heath Hero in the innovations category. Michael is passionate about community-based eye banking and honoring the precious gift that is donation. When not at work, he enjoys traveling with his wife and baking artisan sourdough bread.