Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease

Abstract

Purpose: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD).

Methods: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC.

Results: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02).

Conclusion: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development.

Keywords: Allogeneic hematopoietic stem cell transplant; Cicatrizing conjunctivitis; Conjunctival fibrosis; Graft versus host disease; Immune-mediated ocular disorders; Immunopathology; Ocular graft versus host disease; Ocular surface disease.

Figure 1:. Incidence of Cicatrizing Conjunctivitis in Chronic Ocular Graft-versus-Host-Disease

Estimated incidence of chronic cicatrizing conjunctivitis in individuals with chronic ocular graft-versus-host disease over a 120-month period.

Figure 2:. Distribution of Chronic Cicatrizing Conjunctivitis (CCC) severity in 167 individuals with Chronic Ocular Graft-versus-Host-Disease based on the Foster Classification System.

The frequency reflects the most advanced stage of chronic cicatrizing conjunctivitis in either eye at the end of each individual’s follow-up period. CCC: Chronic cicatrizing conjunctivitis; Stage 1: Subepithelial fibrosis; Stage 2: Inferior fornix shortening; Stage 3: Symblepharon; Stage 4: Ankyloblepharon with severe sicca syndrome and keratinization of the ocular surface.

Figure 3:. Features of Chronic Cicatrizing Conjunctivitis in the Setting of Chronic Ocular Graft-versus-Host-Disease

A. Slit lamp photograph of the left eye of an individual with chronic cicatrizing conjunctivitis in the setting of chronic ocular graft-versus-host-disease demonstrating subtarsal fibrosis of the upper eyelid (arrow). B. Slit lamp photograph of the left eye of an individual with chronic cicatrizing conjunctivitis in the setting of chronic ocular graft-versus-host disease demonstrating subtarsal fibrosis with mild forniceal shortening in the lower eyelid (arrow). C. Slit lamp photograph of the left eye of an individual with chronic cicatrizing conjunctivitis in the setting of chronic ocular graft-versus-host-disease demonstrating an inferonasal symblepharon (arrow) as well as central corneal thinning with pigmentation in the area of prior perforation.

Figure 4:. Complications of Chronic Cicatrizing Conjunctivitis in the Setting of Chronic Ocular Graft-versus-Host-Disease

A. Slit lamp photograph of the left eye of an individual with chronic cicatrizing conjunctivitis in the setting of chronic ocular graft-versus-host disease demonstrating subtarsal fibrosis of the upper eyelid (arrows) leading to disruption of the upper lid margin. B. Slit lamp photograph of the left eye showing upper eyelid entropion and trichiasis temporally, with medial lashes removed due to trichiasis. Circumferential limbal stem cell deficiency can also be appreciated along with diffuse corneal haze with superior scarring with vascularization.