Primary Immune Deficiency Disease (PIDD) is a group of genetic disorders that affect the innate and adaptive immune system [
A 13-year-old child with learning disability was referred for ophthalmic assessment as she complained of bilateral blurring of vision. At presentation, her visual acuity was 1/60 in the right eye and 6/18 in the left eye. Relative afferent pupillary defect (RAPD) was present in the right eye. Both eyes anterior segment examination findings were normal. Grade 1 vitritis was noted in the right eye. Funduscopic examination of the right eye revealed a pale optic disc and pigmented scar over the macula with salt and pepper appearance. Intense retinitis with focal areas of haemorrhage was present nasally (Figure
Right eye prior to treatment.
Left eye prior to treatment.
Systematically, she was diagnosed with combined T and B cell deficiencies by the immunologist at the age of 11. At that time, she presented with high fever, recurrent episodes of diarrhoea, oral thrush, and failure to thrive, with the weight of only 12kg. PIDD screening showed low T cell, very low B cell counts, and low immunoglobulin levels (Table
PIDD screening.
| | |||
---|---|---|---|---|
| | | | |
Total T cells | 38 | 802 | 66-76 | 1400-2000 |
Total B cells | 0 | 7 | 12-22 | 300-500 |
Th cells (CD4) | 10 | 176 | 33-41 | 700-1000 |
Ts cells (CD8) | 24 | 440 | 27-35 | 600-900 |
NK cells | 59 | 1428 | 9-16 | 200-600 |
| | |
---|---|---|
IgG | 613 | 931-1916 |
IgA | 134 | 70-473 |
IgM | 117 | 34-265 |
IgE | 121 | <165 |
We diagnosed the child of having bilateral eye CMV retinitis based on typical fundus features and history of treated CMV colitis. She was planned for right eye intravitreal ganciclovir injection in view of poor visual function with posterior pole involvement. However, she was deemed unfit to undergo general anaesthesia due to concomitant hospital acquired pneumonia. IV ganciclovir 75mg (6mg/kg) 12 hourly was started and good response was noted after 2 weeks of therapy (Figure
Right eye 2 weeks after IV ganciclovir.
Right eye after completion of 8 weeks of IV ganciclovir (a). Left eye after completion of 8 weeks of IV ganciclovir (b).
CMV retinitis can occur in patients with impaired T- cell response such as in solid organ transplant, bone marrow transplant, PIDD, AIDS, or those on immunosuppressive therapy [
The diagnosis of CMV retinitis in this child was established late as evident by bilateral and zone 1 involvement. Patients, especially children with early peripheral CMV retinitis often do not notice the subtle symptoms such as mild blurring of vision, loss of peripheral vision, floaters, or scotoma. Significant visual loss in her right eye is mainly attributed to aggressive extension of retinitis to the optic nerve and macula. Despite achieving resolution of retinitis with antiviral therapy, her visual outcome remained poor.
In AIDS patients, extraocular CMV disease seems to be a strong predisposing factor for developing CMV retinitis. A study has shown that 85% AIDS patients with extraocular CMV disease subsequently developed CMV retinitis after a mean of 6.4 months [
Treatment strategies which include choice of antiviral and its duration for CMV retinitis in human immunodeficiency virus (HIV) negative patients are vague, particularly in the paediatric group. We have extrapolated the treatment approach used in HIV-infected children with CMV disease in this case. IV ganciclovir, IV foscarnet, IV cidofovir and oral valganciclovir are choices of antiviral available for CMV retinitis in both adults and children. Ganciclovir sustained-release intraocular implant is no longer being manufactured. The treatment guidelines from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America recommended IV ganciclovir 6 mg/kg body weight/dose administered 12 hourly as initial treatment for HIV-infected infants with CMV disease [
Valganciclovir, the oral prodrug of ganciclovir, has been well established to be as effective as IV ganciclovir for induction and maintenance therapy of CMV retinitis in HIV adult patients [
For Zone 1 disease, intensive administration of intravitreal ganciclovir and/or foscarnet given concomitantly with systemic antiviral has been suggested [
The severity and location of retinitis, patient’s systemic condition, and complications and response to treatment need to be tailored accordingly. IV ganciclovir 6 mg/kg body weight/dose administered 12 hourly was started in this case. We intended for intravitreal injection in this case but, after discussion with the paediatricians and anaesthetists, biweekly intravitreal injection was not feasible due to her multiple systemic comorbidities. Within 2 weeks of treatment with IV ganciclovir, we noted substantial regression of retinitis in the child. Hence, additional antiviral agents were not considered. After complete regression of retinitis with IV ganciclovir, oral valganciclovir as a maintenance is preferred due to its more convenient administration. Unfortunately, it was not available in our setting. As all current antiviral therapies for CMV retinitis are virostatic [
In this case, zone 1 CMV retinitis was diagnosed late and suboptimal treatment was given due to her underlying systemic disease. Hence, although there was eventual resolution of the retinitis after 8 weeks of intravenous therapy, the visual acuity deteriorated due to progressive optic nerve involvement from the retinitis. This highlights the importance of a high index of suspicion with timely referral to prevent irreversible visual loss in these patients. The importance of good teamwork between the Paediatrician, Anaesthetist, and Ophthalmologist may ensure optimal treatment, thus preventing blinding complications of CMV retinitis in children with PIDD.
Consent to publish was not obtained. No information in this case report that could lead to identification of the patient.
All authors report no conflicts of interest.