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Corneal perforation in ocular graft-versus-host disease
Cathy Y Zhang1, Asim V Farooq2, George J Harocopos1,3
1Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, 63110, United States.
Insights
Corneal perforation after ocular graft-versus-host disease (GVHD) is a serious complication. A significant time gap exists between ocular GVHD diagnosis and perforation, offering a window for preventative strategies.
Area of Science:
- Ophthalmology
- Hematology
- Immunology
Background:
- Ocular graft-versus-host disease (GVHD) is a rare complication following hematopoietic stem cell transplant (HSCT).
- Corneal perforation is a severe, vision-threatening manifestation of ocular GVHD, with limited understanding of its clinical progression.
Purpose of the Study:
- To investigate the clinical course and histopathologic findings in patients who developed corneal perforation secondary to ocular GVHD.
- To identify potential risk factors and timing associated with corneal perforation in ocular GVHD patients.
Main Methods:
- Retrospective case series involving 14 patients from four academic centers.
- Analysis of patient demographics, HSCT details, ocular GVHD timeline, visual acuity, interventions, and histopathology.
- Correlating clinical presentation with histopathologic findings of corneal perforation.
Main Results:
- The average age at HSCT was 47 years, with most patients being male and Caucasian.
- Mean interval from HSCT to ocular GVHD diagnosis was 9.5 months, and to corneal perforation was 37 months.
- All patients experienced poor visual outcomes despite aggressive management, including corneal gluing and keratoplasty; histopathology suggested sterile corneal melt.
Conclusions:
- An extended interval between ocular GVHD diagnosis and corneal perforation was observed.
- This interval presents a critical opportunity for intervention to prevent perforation.
- Further research is needed to identify high-risk patients and optimize preventive measures.
Purpose:
Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome.
Methods:
This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology.
Results:
Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal "melt" in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar.
Conclusions:
In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies.
