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. 2022 May 3:16:1419-1426.
doi: 10.2147/OPTH.S359539. eCollection 2022.

Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study

Bradley A Colarusso  1 , Shannon M Bligdon  2 , Allen Y Ganjei  3 , Alan Kwok  4 , Daniel Brocks  4 , Zhonghui K Luo  1
Affiliations

Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study

Bradley A Colarusso et al. Clin Ophthalmol. .

Abstract

Purpose: To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Patients and methods: A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed.

Results: Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms.

Conclusion: oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.

Keywords: cGVHD; dry eye; hematopoietic stem cell transplantation; keratoconjunctivitis sicca; oGVHD.

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Conflict of interest statement

A. Kwok and D. Brocks are salaried employees of BostonSight, Needham, MA, where BostonSight PROSE treatment and BostonSight SCLERAL lenses were developed. None of the authors have a financial or any other conflict of interest in this work.

Figures

Figure 1
Figure 1
335 subjects reported their ocular symptom onset in relation to the time of their allo-HSCT. There were 6 individuals with symptom onset before allo-HSCT that remained stable, 23 with pre-existing symptoms that worsened after allo-HSCT, and 306 with symptoms onset after allo-HSCT. The number of subjects were further arranged according to the number of symptoms they experienced.
Figure 2
Figure 2
Percentage of subjects whose ocular symptom onset (a total of 306 subjects represented with clear bars) or worsening (a total of 23 subjects represented with grey bars) occurred at different times after allo-HSCT. The actual number of subjects is labeled above each bar.
Figure 3
Figure 3
The diagnoses of oGVHD and systemic cGVHD reported by the 335 subjects with ocular symptoms. The actual number of subjects is labeled above each bar.
Figure 4
Figure 4
The diagnosis of oGVHD graphed against the number of symptoms, treatments tried, and subjective level of symptom control. (A) A total of 301 subjects reported their levels of symptom control. The percentage of subjects with or without the diagnosis of oGVHD is graphed in each group. (B) The percentage of the 335 symptomatic subjects with or without a diagnosis of oGVHD is graphed against the number of symptoms reported. (C) The percentage of the 335 symptomatic subjects with or without a diagnosis of oGVHD is graphed against the number of treatments tried. The actual number of subjects is labeled above each bar.
See this image and copyright information in PMC

References

    1. Ogawa Y, Kawakami Y, Tsubota K. Cascade of inflammatory, fibrotic processes, and stress-induced senescence in chronic GVHD-related dry eye disease. Int J Mol Sci. 2021;22:11. doi:10.3390/ijms22116114 - DOI - PMC - PubMed
    1. Munir SZ, Aylward J. A review of ocular Graft-versus-Host Disease. Optom Vis Sci. 2017;94(5):11. doi:10.1097/OPX.0000000000001071 - DOI - PubMed
    1. Nassiri N, Eslani M, Panahi N, Mehravaran S, Ziaei A, Djalilian AR. Ocular graft versus host disease following allogeneic stem cell transplantation: a review of current knowledge and recommendations. J Ophthalmic Vis Res. 2013;8(4):8. - PMC - PubMed
    1. Shikari H, Antin JH, Dana R. Ocular Graft-versus-Host Disease: a review. Surv Ophthalmol. 2013;58(3):233–251. doi:10.1016/j.survophthal.2012.08.004 - DOI - PubMed
    1. Hirst LW, Jabs DA, Tutschka PJ, Green WR, Santos GW. The eye in bone marrow transplantation I. Clin Study. 1983;101(4):5. - PubMed