Early treatment of GVHD in the ophthalmology setting is critical

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Reviewed by Vishal Jhanji, MD

A variety of treatments can be employed to treat ocular graft-vs-host disease (GVHD) when it presents to an ophthalmologist, according to Vishal Jhanji, MD, a professor of ophthalmology at the University of Pittsburgh School of Medicine in Pennsylvania. Delivering the Bruce Jackson Lecture—“Ocular GVHD: Not the Garden Variety Dry Eye”—at the 2023 Canadian Ophthalmology Society Annual Meeting and Exhibition, Jhanji, a corneal specialist, emphasized that ophthalmologists must work with the transplant team to detect ocular GVHD as early as possible.

To Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is particularly associated with the emergence of ocular GVHD.¹ Ocular GVHD is not discussed much because transplant patients likely have multiple health concerns other than what is going on with their eyes, Jhanji explained.

“One of the reasons ocular GVHD is not talked about much is because eyes are not the major concern for these patients,” Jhanji said. “That is why one of the main issues that we see in ocular GVHD is a late diagnosis. These patients are going through a lot.”

Clinicians performing the bone marrow transplants are aware that patients can develop ocular GVHD, especially patients who develop chronic GVHD, according to Jhanji. “The issue is awareness of existence of ocular GVHD, and the need for teamwork between ophthalmology and the bone marrow transplant doctor,” Jhanji pointed out. “It would really help these patients to see an ophthalmologist for timely diagnosis and treatment. It is important that there is a high index of suspicion in order not to miss the diagnosis in patients.”

If the ophthalmologist has an opportunity to see the patient prior to surgery, they should check for their baseline dry eye and determine the type of dry eye, Jhanji noted. “If patients have baseline aqueous deficient or inflammatory dry eye, treating that dry eye before the transplant will certainly help in the event these patients develop ocular GVHD,” Jhanji added.

Treating ocular GVHD

The diagnostic criteria for ocular GVHD are based on parameters including ocular surface disease index, corneal fluorescein staining, and conjunctival injection; treatment is based on the severity of the disease, Jhanji noted. Preservative-free artificial tear drops help with ocular symptoms, according to Jhanji.

“Treatment is mainly with corticosteroid eye drops,” Jhanji said. “Long-term use of prednisone eye drops is associated with adverse effects (notably cataract and glaucoma). A less potent form of steroid, such as loteprednol and fluorometholone, might be a suitable alternative especially because these patients would likely need corticosteroid eye drops for a long time. We need to be selective and careful so that the steroids do not cause more [adverse] effects in these patients who have ocular side effects of GVHD.”

As an anti-inflammatory treatment option, cyclosporine eye drops are used in patients with treatment-refractory dry eye disease. The concentration of cyclosporine eye drops can vary from 0.05% to 0.1%, with a higher concentration of eye drops initiated if necessary, Jhanji said.

Topical treatments

Other topical treatments include autologous serum eye drops and platelet-rich plasma eye drops. The blood-based treatment options might not be easily available, Jhanji explained.

Meibomian gland dysfunction is one of the hallmarks of ocular GVHD. Improving the lipid layer of the tear film with viscous eye drops and ointments improves the meibomian gland outflow, he explained.

Antibiotics are also part of the armamentarium, Jhanji noted. “We do use doxycycline depending on the severity of the disease,” he added.

One of the modalities to treat ocular GVHD is the use of scleral lenses, which provide clear vision. “These specialized lenses rest on the sclera, far away from the limbus. They do not need a lot of maintenance, but they can be cost-prohibitive,” Jhanji said. “The use of scleral lenses has been shown to reduce ocular pain associated with GVHD. In addition, the lenses protect the cornea from the irritation caused by blinking and the outside environment.”

Systemic treatment might help with ocular symptoms as well, said Jhanji, who discussed a recent experience with the Janus kinase inhibitor ruxolitinib, which has been approved for steroid-refractory chronic GVHD.² Still another experience with belumosudil, an inhibitor of Rho-associated coiled-coil–containing protein kinase 2 that has been approved for treatment of steroid-refractory chronic GVHD, demonstrated efficacy.³ “Both have been shown to be effective in a proportion of patients with ocular GVHD,” Jhanji said.

Future research and follow-up of patients with ocular GVHD

It is important to liaise with the bone marrow transplant team while managing ocular GVHD in patients, Jhanji emphasized. “Early detection of the ocular symptoms might help to alleviate ocular symptoms associated with the long-term inflammatory process,” he added. One of the future objectives should be to collect data on treatment outcomes with ocular GVHD through ongoing follow-up of patients, with a goal of supporting preventive strategies and therapeutic interventions, according to Jhanji.

Vishal Jhanji, MD

P: 412-647-2200

Jhanji has no financial disclosures related to this content. This article is based on his presentation at the Canadian Ophthalmological Society Annual Meeting and Exhibition, held June 15 to 18, 2023, at the Québec City Convention Centre in Canada.

References:

1. Pathak M, Diep PP, Lai X, Brinch L, Ruud E, Drolsum L. Ocular findings and ocular graft-versus-host disease after allogeneic stem cell transplantation without total body irradiation. Bone Marrow Transplant. 2018;53(7):863-872. doi:10.1038/s41409-018-0090-z

2. Zeiser R, Polverelli N, Ram R, et al; REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238. doi:10.1056/NEJMoa2033122

3. Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;138(22):2278-2289. doi:10.1182/blood.2021012021