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    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    8 External Disease and Cornea

    Chapter 11: Diagnosis and Management of Immune-Related Disorders of the External Eye

    Immune-Mediated Disorders of the Conjunctiva

    Ocular Graft-vs-Host Disease

    PATHOGENESIS

    The pathogenesis of ocular surface disease in graft-vs-host disease (GVHD) is multifactorial but has 2 main components: (1) conjunctival inflammation with or without subepithelial fibrosis and (2) severe keratoconjunctivitis sicca (KCS) from lacrimal gland infiltration. KCS occurs in 40%–60% of patients with chronic GVHD (cGVHD).

    GVHD is a relatively common complication of allogeneic bone marrow transplantation, which is performed most commonly for hematopoietic malignancies. In this condition, the grafted cells can attack the patient’s tissues, including the skin, gut, lungs, liver, gastrointestinal tract, and eyes. GVHD can be acute or chronic (developing more than 3 months after a bone marrow transplant), with most ocular complications occurring as a manifestation of cGVHD.

    Jabs DA, Wingard J, Green WR, Farmer ER, Vogelsang G, Saral R. The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease. Arch Ophthalmol. 1989;107(9): 1343–1348.

    CLINICAL PRESENTATION

    The clinical features of ocular GVHD (eg, KCS, cicatricial conjunctivitis, scleritis) mirror those of other ocular inflammatory conditions associated with autoimmune and collagen-vascular diseases. Conjunctival inflammation in GVHD, which can be severe, may be associated with limbal stem cell deficiency and secondary corneal scarring, although fortunately, this inflammation is rare.

    Inamoto Y, Chai X, Kurland BF, et al. Validation of measurement scales in ocular graft-versus-host disease. Ophthalmology. 2012;119(3):487–493.

    Lin X, Cavanagh HD. Ocular manifestations of graft-versus-host disease: 10 years’ experience. Clin Ophthalmol. 2015;9:1209–1213.

    Ogawa Y, Shimmura S, Dogru M, Tsubota K. Immune processes and pathogenic fibrosis in ocular chronic graft-versus-host disease and clinical manifestations after allogeneic hematopoietic stem cell transplantation. Cornea. 2010;29(11):S68–S77.

    MANAGEMENT

    These patients should be approached in a stepwise, multimodal fashion in consultation with their hematologist and/or oncologist. Aggressive ocular lubrication and punctal occlusion are the mainstays of local therapy. Punctal fibrosis is common and must be monitored closely because it can lead to plug extrusion. Severe filamentary keratitis can be treated with mucolytic agents (acetylcysteine 10%) or bandage contact lenses. Topical cyclosporine or tacrolimus may also be useful in controlling ocular GVHD. Visual disturbances are more commonly due to surface irregularity, but these patients also have a high rate of posterior subcapsular cataracts, which contribute to decreased vision. Autologous serum tears may also be considered. Gas-permeable scleral contact lenses, therapeutic soft contact lenses (Fig 11-14), and the PROSE treatment (discussed earlier in the chapter) can be important management tools for patients with severe ocular surface disease. Keratoprosthesis may be a last-resort option for patients with end-stage ocular surface disease who are not candidates for other conventional corneal procedures. Severe GVHD may require systemic therapy.

    DeLoss KS, Le HG, Gire A, Chiu GB, Jacobs DS, Carrasquillo KG. PROSE treatment for ocular chronic graft-versus-host disease as a clinical network expands. Eye Contact Lens. 2016; 42(4):262–266.

    Dietrich-Ntoukas T, Steven P. Ocular graft-versus-host disease. Ophthalmologe. 2015;112(12): 1027–1040.

    Jung JW, Lee YJ, Yoon SC, Kim TI, Kim EK, Seo KY. Long-term result of maintenance treatment with tacrolimus ointment in chronic ocular graft-versus-host disease. Am J Ophthalmol. 2015;159(3):519–527.

    Liu C, Okera S, Tandon R, Herold J, Hull C, Thorp S. Visual rehabilitation in end-stage inflammatory ocular surface disease with the osteo-odonto-keratoprosthesis: results from the UK. Br J Ophthalmol. 2008;92(9):1211–1217.

    Malta JB, Soong HK, Shtein RM, et al. Treatment of ocular graft-versus-host disease with topical cyclosporine 0.05%. Cornea. 2010;29(12):1392–1396.

    Figure 11-14 A, Patient with graft-vs-host disease fitted with a therapeutic scleral contact lens. The inferior paracentral cornea demonstrates subepithelial scarring. B, High magnification shows the space between the contact lens and cornea.

    (Courtesy of Charles S. Bouchard, MD.)

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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