Dr. Vishal Jhanji provided a brief overview of ocular GVHD at the All India Ophthalmology Society (AIOS) International Ophthalmic Conclave (IOC) 2022, including identification of the disease, its effects, and current and future treatment options…
Ocular graft versus host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplant (allo-HSCT). It arises after donor heme cells taken from bone marrow activate the body’s natural immune response and T cells begin to attack, causing ocular GVHD. In his presentation at AIOS IOC 2022, Dr. Vishal Jhanji stressed the importance of recognizing, understanding and treating this complex disease.
Acute Ocular GVHD
Ocular GVHD comes in two types: acute and chronic. The acute variation is ocular GVHD that manifests itself within the first 100 days of transplantation. Dr. Jhanji underlined the urgency of early diagnosis, as acute ocular GVHD can be a prognostic factor for higher mortality.
Acute ocular GVHD includes symptoms such as eye pain, redness and excessive tearing. He pointed to conjunctival involvement as a hallmark of acute GVHD. “Chemosis is massive sometimes — you see pseudomembranes, symblepharon almost like a cicatricial disease presentation, but in acute form,” he said. “I have seen some patients with corneal ulceration in acute GVHD and they are really difficult to manage. Saving the eye is very difficult in these patients.”
Chronic Ocular GVHD
Chronic ocular GVHD is far less severe and far more common, with Dr. Jhanji citing 40-60% ocular involvement in chronic patients.
Common symptoms include patient reports of a dry, gritty sensation (or foreign bodies), and photophobia. He highlighted three important processes in the progression of ocular GVHD: lacrimal gland dysfunction, meibomian gland dysfunction, and corneo-conjunctival inflammation, which is a highlight of the disease. Scleritis, anterior uveitis, vitritis, retinal hemorrhages and CWS, and serous choroidal detachment are more rarely occurring symptoms.
Identifying Ocular GVHD
For identifying the progression of the disease, Dr. Jhanji recommended the Wratten filter during staining for the best results. “What I have noticed is that the corneal staining can sometimes be very patchy. One quadrant would be involved focally in these patients, and the rest of the cornea might not look too bad,” he shared. He also noted the high prevalence of filaments in acute and acute-on-chronic ocular GVHD patients.
Showing a slide of a patient displaying corneo-conjunctival symptoms, he pointed out excessive staining on the cornea, while also noting that conjunctival involvement is significant in such patients.
Two major types of scarring may occur with ocular GVHD patients: tarsal scarring and corneal scarring. With tarsal scarring, the involved glands are destroyed and subtarsal fibrosis takes over, resulting in almost permanent dryness. For corneal scarring, Dr. Jhanji described a case where he performed a tarsorrhaphy on an infected eye, resulting in a corneal scar.
He also presented slides of a patient with acute-on-chronic GVHD with a corneal epithelial defect. “The epithelial defect is so chronic — almost calcareous degeneration,” he said, noting that this was another hallmark of chronic ocular GVHD.
Treatment for GVHD
Dr. Jhanji established two cornerstones of ocular GVHD treatment: reducing ocular surface inflammation to reduce cicatricial changes, and regularly updating the hematology/oncology team.
For preventing tear evaporation, Dr. Jhanji recommended aggressively maintaining lid hygiene with warm compresses and lid scrubs and using moisture chamber goggles. Topical erythromycin ointment is preferred to tetracyclines, as patients are already taking a variety of other drugs.
Lubrication and tear preservation can be managed with preservative-free artificial tears during the day and ointment at bedtime. He suggested acetylcysteine (5% or 10%) for filamentary keratitis. If using oral secretagogues, and especially pilocarpine, keeping the hematology team and the PCP involved to prevent side effects is crucial. Autologous serum tears are a mainstay for maintaining lubrication, and he praised the use of scleral lenses for chronic patients.
Dr. Jhanji argued against the use of punctal occlusion in treating ocular GVHD, as inflammatory material must be cleared from the eye and occluding the puncta makes controlling inflammation difficult.
Restasis is the standard for reducing any ocular surface inflammation, but topical cyclosporine and topical tacrolimus were mentioned as alternatives.
Although surgical intervention is rarely needed, amniotic membranes can be used for patients with a poor corneal epithelium and tarsorrhaphy for those with persistent epithelial defects. Also listed as possible surgical procedures for ocular GVHD were tectonic patch grafts and penetrating keratoplasty.
Treatments on the Horizon for Ocular GVHD
A variety of treatments are under development for sufferers of ocular GVHD. The topical secretagogues diquafosol and rebamipide, which increase mucin production and have anti-inflammatory effects, are in regular use in many countries but are unavailable in the United States. Topical IVIG drops, currently in phase II clinical trials conducted by Sandeep Jhain at UIC, have shown great efficacy in reducing dry eye disease associated with the disease.
Dr. Jhanji referenced an encouraging phase I/phase II clinical trial he took part in using a topical fibrinogen-depleted human platelet lysate.
Topical heparin eyedrops are also a potential area of interest, as it clear neutrophil extracellular traps, which supposedly worsen the disease. Heparin also has antifibrotic and immunosuppressive effects that can help in these patients.
The final experimental drug he pointed to was entospletinib, a selective inhibitor of spleen tyrosine kinase used primarily in the treatment of various types of cancers. A secondary benefit for ocular GVHD was observed in mice eyes, but the use of this drug is still in its early stages.
Prevention of Ocular GVHD
The first line of defense against ocular GVHD is prophylaxis, and Dr. Jhanji stressed, in addition to staying in touch with the hematology/oncology team and conducting a comprehensive eye examination before or within 6 months of the allo-HSCT treatment.
Also mentioned was a study from Mexico, where topical cyclosporine (0.05%) started after HSCT for one year showed promise in preventing ocular GVHD. Although 45-50% of the patients in this study developed extra-ocular GVHD, a mere 1 in 20 saw the development of ocular GVHD.
Editor’s Note: The All India Ophthalmology Society’s 2nd International Ophthalmic Conclave (AIOS IOC 2022) was held virtually from February 18-20, 2022. Reporting for this story took place during the event.
