CVID is characterized by recurrent sinopulmonary infections, decreased levels of immunoglobulin, and impaired functional antibody responses. The prevalence of CVID is reported to range from one in 50,000 to one in 200,000 [1]. Patients with CVID present with a bimodal age distribution with the majority diagnosed either in childhood or in their second or third decade of life, although some patients present later in their adult life [1]. Autoimmune diseases, including lichen planus [2], are also seen in approximately 25 % of patients with CVID [1].
Cases of corneal disease in patients with CVID are limited in the literature. These studies suggest that keratitis in CVID may manifest as infectious and/or inflammatory in nature [3, 4]. Bilateral consecutive sterile corneal thinning that progressed to perforations was reported in a patient with CVID by Akpek et al. [3]. In this case, multiple scrapings, biopsies, and cultures remained sterile and the corneal infiltrates showed no response to antibiotics but disappeared with topical steroid therapy. It was postulated that the corneal perforations may have initially been due to an autoimmune etiology and then complicated by a secondary Haemophilus influenzae endophthalmitis. Though we eventually isolated MRSA from the cornea of our patient, her initial presentation appeared more consistent with a sterile melt (intact epithelium and no infiltrate) and she did not have the typical risk factors for infectious keratitis such as trauma, contact lens wear, or lagophthalmos. Our eventual recovery of MRSA from her cornea and later from her conjunctiva suggests that it is prudent to maintain a high level of suspicion for an infectious etiology in patients with ocular surface disease and CVID even if their initial presentation does not appear to be typical of an infection.
Reports of other ocular manifestations in CVID are also limited and include retinal vasculitis [4], uveitis [4], keratoconjunctivitis [5, 6], and episodic retinal vein occlusions [7]. In several of these cases, initiation of treatment of IVIG and/or steroids led to the resolution of uveitis or granulomatous lesions [4, 5] and recurrent keratoconjunctivitis [5]. Patients that have CVID may require lifelong immunoglobulin replacement to prevent further ocular and systemic manifestations of disease. Corneal cultures may be indicated to evaluate for an infectious etiology, such as in the case presented above. It may be prudent to start patients on empiric topical antibiotics and steroids, given the devastating sequelae seen in the case by Akpek et al. [3].
Common organisms isolated from ocular infections in patients with CVID are S. aureus and encapsulated bacteria, such as Streptococcus pneumoniae and H. influenzae. Ocular infections with these organisms primarily involve the conjunctiva and secondarily involve the cornea. A study by Franklin et al. included five patients with CVID over 2 years. Conjunctival cultures from three patients grew H. influenzae, one culture grew Staphylococcus epidermidis, and one grew S. aureus [8]. Similarly, a patient with multi-organism keratoconjunctivitis described by Ooi et al. had conjunctival cultures that grew H. influenzae and S. aureus [5]. The patient in the case reported by Akpek et al. eventually developed a secondary endophthalmitis due to H. influenzae [3].
Systemic administration of IVIG is the primary treatment for many forms of hypogammaglobulinemia, including CVID. However, it has been demonstrated that even in immunocompetent individuals, levels of immunoglobulins in the tear film do not reflect those in the serum suggesting autonomous local regulation of immunoglobulin [9]. Indeed, it has been established that ocular immunoglobulins are produced locally by both the lacrimal gland and the eye-associated lymphoid tissue in the conjunctiva [10]. Further, IVIG only includes IgG and not other isotypes, such as IgA, the primary immunoglobulin responsible for mucosal defense. Although tear film immunoglobulin levels in patients with CVID have not been studied, it can be conjectured that tear film immunoglobulins are also decreased. Therefore, mucosal defense at the ocular surface could remain susceptible despite systemic IVIG treatment. Further complicating diagnosis and treatment is the fact that while CVID is a form of immunosuppression, it is also associated with autoimmune disease. As noted above, our patient had lichen planus for which she was receiving oral cyclosporine adding to her impaired immune response to corneal infection. We postulate that the combination of CVID and treatment with cyclosporine account for the development and atypical presentation of bacterial keratitis in this patient.
In conclusion, patients with CVID on monthly IVIG infusions may still develop infectious diseases of the ocular surface without the typical findings of bacterial infection. Investigation for an infectious etiology should be performed and treatment promptly implemented when presented with conjunctival or corneal inflammation or ulceration.