ABSTRACT

We present a case of infectious crystalline keratopathy in a patient with Graft-versus-Host disease who developed satellite fungal keratitis. A 51-year-old man was referred for bilateral total persistent corneal epithelial defects with severe dry eye. Although persistent epithelial defect healed with medical therapy, he developed stromal keratitis with satellite lesions confirmed to be secondary to Candida albicans. After three months of antifungal treatment and debridement, improvement of the infiltrates was obtained. Crystalline keratopathy is an important clinical entity which may develop due to several causes. The microbial causes include not only bacteria but fungi as well. Careful investigation must be performed, especially for immune-compromised patients, in order to provide appropriate and timely treatment.

Introduction

Crystalline keratopathy is a condition in which crystals are deposited in the anterior and/or mid-corneal stroma. Crystalline keratopathy of the cornea may be caused by several conditions including corneal dystrophies or systemic disorders, elevated serum immunoglobulins, corneal infections, or rejection of corneal grafts.^1,2,3

Affected individuals present to ophthalmologists with symptoms of pain, redness, photophobia, and decreased vision. Clinical examination usually reveals conjunctival injection, chemosis, and corneal changes, which include branching crystalline opacities in the anterior/mid-corneal stroma associated with epitheliopathy.^4,5

We present a unique case of a patient with graft-versus-host disease (GVHD) and crystalline keratopathy who developed keratitis with satellite lesions secondary to fungal keratitis, which regressed with antifungal treatment and corneal debridement.

Discussion

GVHD is a devastating complication of allogeneic stem cell transplantation. The incidence of ocular GVHD is high after stem cell transplantation,12 ker1junctivitis sicca and cicatricial conjunctivitis are two common ocular manifestations of this disease.⁷

Ocular involvement in Figure1 appears as inflammatory destruction of the conjunctiva and lacrimal glands with fibrosis, decreased goblet cell density, and a resultant decrease in tear production.⁸ Major findings in the conjunctiva and cornea include punctate keratopathy, keratinization, epithelial thinning, and squamous metaplasia.⁹ Pseudomembranous pattern with corneal epithelial sloughing is generally considered an acute pattern of chronic ocular GVHD¹⁰, which was thought to be the reason for development of keratitis in our case since epithelial barrier function was impaired.

In the presence of certain risk factors, such as corneal hypoesthesia, diabetic keratopathy, limbal stem cell deficiency, dry eye disease, and certain keratopathies, epithelial defects can persist despite standard therapies. When a patient shows no response to treatment after approximately two weeks, they are said to have a PED.¹¹ Aggressive lubrication, bandage soft and scleral contact lenses, pressure patching, autologous serum, punctal occlusion, debridement, amniotic membrane grafting, and limbal stem cell transplantation are some of the treatment options for PED.¹² In our case, punctal occlusion, aggressive lubrication and autologous serum eye drops were used, as well as a novel matrix regenerating agent (Cacicol 20^®, polycarboxymethylglucose sulfate, Thea Lab). Cacicol, which is a structural analogue of glycosaminoglycans, mimics heparin sulfate (HS) and is thought to replace the degraded HS and produce a suitable environment for recruiting growth factors necessary for corneal repair, especially in eyes with PED.¹³

Cases of crystalline keratopathy secondary to fungi have been presented in the literature.1 In the present case, the crystalline keratopathy developed in a GVHD patient resolved after antifungal therapy, which indicates that the causative agent might have been fungi. Infectious crystalline keratopathy may arise de novo or after surgical procedures such as refractive surgery or penetrating keratoplasty.^4,5 Streptococcus viridans is the most common organism to cause crystal deposits followed by Staphylococcus epidermidis, Streptococcus pneumonia, Haemophilus spp., and enterococci.¹ However, Candida spp. and atypical organisms such as mycobacteria must be kept in mind, especially in immune-suppressed conditions such as patients who use chronic corticosteroids or abuse topical anesthetic eye drops.¹⁴

When the clinical course of our patient was reviewed, it could not be ascertained whether the crystalline keratopathy initially observed was secondary to fungal infection. However, the size and number of crystals in crystalline keratopathy regression strongly suggests a fungal etiology. On the other hand, our patient had been immune-compromised and he had epithelial irregularity, PED, and severe dry eye secondary to GVHD, which may have an impact on the development of corneal infection. To draw a conclusion, we believe that ophthalmologists must be ready for various clinical courses in a patient with GVHD and that fungal and opportunistic pathogens must be kept in mind while dealing with infections, especially when epithelial integrity is lost.