Dyskeratosis Congenita and Corneal Refractive Surgery
Dyskeratosis congenita is a syndrome of bone marrow failure secondary to unstable telomeres. It is characterized by a range of mucocutaneous diseases. Due to premature telomere shortening, these patients have limbal stem cell deficiency leading to poor regeneration and maintenance of the cornea. Many of these patients will require hematopoietic stem cell transplant in their lifetime, which poses a significant risk for acute and chronic graft-versus-host disease with and without ocular manifestations. We advise against elective corneal refractive surgery in patients with dyskeratosis congenita due to the compounded and long-term risks of delayed healing secondary to limbal stem cell deficiency and ocular complications of graft-versus-host disease post-allogeneic hematopoietic stem cell transplant.
KeywordsBone marrow failure Cornea refractive surgery Dyskeratosis congenita Graft-versus-host disease Laser in situ keratomileusis (LASIK) Limbal stem cell deficiency Ocular manifestations of graft-versus-host disease Photorefractive keratectomy (PRK) Small-incision lenticule extraction (SMILE) Telomeres
DC is phenotypically heterogeneous, and patients also present with features such as developmental delay, pulmonary fibrosis, and diseases affecting multiple organs like the eyes, liver, esophagus, and periodontal areas [1, 5]. Ocular findings in DC vary according to patient phenotype, with common ocular findings of obstruction of the lacrimal system with epiphora (31%), conjunctivitis, entropion and ectropion, trichiasis, blepharitis, cataract, glaucoma, and exudative retinopathy [1, 3, 12]. Specifically, bilateral exudative retinopathy and intracranial calcifications are associated with a subtype of DC named Revesz syndrome [4, 5]. While some of these findings are contraindications themselves to corneal refractive surgery, we will also address additional complications of DC that we believe to be significant contraindications to elective corneal refractive surgery. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Secondary to the underlying genetic cause of DC, patients are highly susceptible to BMF (up to 80% of patients) with hematopoietic stem cell transplantation (HSCT) as definitive therapy [16, 17]. Due to disease-associated eye disorders in addition to the considerable likelihood of BMF with complications of LSCD and graft-versus-host disease (GVHD) post-bone marrow transplant, we must analyze if a patient with DC is an appropriate candidate for corneal refractive surgery [12, 13, 14]. We conclude that DC patients are not suitable candidates, and we do not recommend any elective corneal refractive surgery such as laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), or small-incision lenticule extraction (SMILE) for DC patients.
At least 80% of patients with DC will experience BMF. Allogeneic HSCT is done to treat this, which puts patients at risk for both acute (< 100 days since transplant) and chronic (> 100 days) GVHD [18, 19]. GVHD is the clinical manifestation of donor T-cells attacking recipient tissue, and ocular manifestations are common . Approximately 40% of individuals who undergo HSCT will experience acute GVHD, and 30% will experience chronic GVHD [20, 21]. Of patients who undergo allogeneic HSCT, 40–60% will have ocular involvement (without GVHD), and 60–90% with acute or chronic GVHD will have ocular manifestations . Ocular GVHD can present as dry eye (most common), keratoconjunctivitis, corneal ulceration, peripheral corneal melting, corneal vascularization, and acquisition of ocular allergy from the donor [19, 22, 23]. Using the mentioned percentages, the lifetime probability of a patient with DC having acute GVHD is 19–29%, and the probability of chronic GVHD with ocular manifestations is 14–22%.
While some patients with DC may not have prominent ocular findings, others will present primarily with eye complaints. Regardless of patient phenotype, the significant likelihood of a DC patient having bone marrow failure and needing hematopoietic stem cell transplant puts these patients at substantial risk for acute and chronic GVHD with or without ocular complications. When considering the impact of limbal stem cell deficiency on healing, in conjunction with allogeneic transplant complications, we do not recommend elective corneal refractive surgery such as LASIK, PRK, or SMILE in patients with DC.
Research to Prevent Blindness NY, NY funded the Rapid Service Fees.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Madeline B. Heiland, Majid Moshirfar, David B. Rosen, Yasmyne C. Ronquillo, and Phillip C. Hoopes have nothing to declare.
Compliance with Ethical Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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