First Author: B.Pershin RUSSIA
Co Author(s): L. Shelihova V. Mahmutov A. Maschan A. Smirnova A. Petuhova
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To present an author-developed protocol of diagnostics and treatment of cytomegalovirus (CMV) retinitis that may develop after haematopoietic stem cell transplantation.
HCMV persists in human organism as a latent infection with no clinical manifestation in an immunocompetent host, but in immunosuppressive setting may cause various severe organic damage including cytomegalovirus retinitis (HCMVR). For children with some forms of hemoblastosis and primary immunodeficiency (HSCT) is the only treatment option.
Development of organic damage, caused by CMV, is preceded by CMV viremia. For its verification the polymerase chain reaction (PCR) of blood should be done weekly. In case of CMV viremia detection the patient requires ophthalmoscopy under mydriasis weekly. In patients with CMV viremia up to 3000 copies/ml ophthalmoscopy under cycloplegia and sclerocompression with sedation and fluorescein angiography should be held once a week until specific anti-CMV lymphocytes appearance in the blood. If white irregular lesions are found in the ocular fundus, intravitreal injection of ganciclovir 2.0 mg with simultaneous intake of intraocular fluid should be done weekly. In case of ganciclovir resistance we perform intravitreal injection of foscavir 2.4 mg. In patients with CMV level in the aqueous humor up to 50000 copies/ml the dose should be increased up to 4.0 mg/0.1 ml. Injections of antiviral medications in the vitreous cavity are performed until repeated PCR negative samples of aqueous fluid and involution of CMV retinitis lesions are registered. Prior to each manipulation a patient undergoes ophthalmoscopy under cycloplegia and fluorescein angiography. After regression of inflammatory lesions and negativization of aqueous fluid PCR all diagnostic procedures should be done weekly until specific anti-CMV lymphocytes appearance in the blood.
Child 1 y.o., with acute myeloblatstic leukemia underwent allogenic HSCT with TCR αβ/ CD 19 depletion from his father. The examination revealed bilateral white irregular lesions of the retina, total size about 7 DD. Fluorescein angiography showed retinal hypoperfusion in inflamed areas in the arterial phase. In the capillary phase we observed accumulation of the dye in the areas of lesions and hyperfluorescence increased with every recirculation cycle. The bilateral acute HCMV retinitis was diagnosed. The patient underwent a number of intravitreal injections of antiviral medications (seven ganciclovir 2.0 mg per 0.1 ml and four foscavir 2.4 mg in 0.1 ml). Injections were performed in the surgery block with simultaneous intake of aqueous humor from anterior chamber. In spite of 3 injections of ganciclovir we observed increase of HCMV copies in the obtained samples up to +76 days. But starting from fourth manipulation we noticed decrease of HCMV in the intraocular fluid with its total elimination after 11 injections of antiviral medications. After each injection inflammatory lesions decreased in size, faded and obtained sharply defined edges. Recovery from HCMVR coincided with appearance of specific anti-HCMV lymphocytes in the peripheral blood.
CMV retinitis in hosts with bone marrow or haematopoietic stem cell transplantation may often cause irreversible blindness as a result of uncontrolled expansion of pathologic lesions in acute period as well as retinal detachment in the longer term. Concerning challenges in visometry in paediatrics, one should keep in mind that manifestation of CMV retinitis may be asymptomatic, particularly if the lesions are localized on the periphery. This means that the only way to preserve vision in children with CMV retinitis is constant ophthalmological monitoring in the posttransplant period. The PCR control of the intraocular fluid of the eye allowed us to monitor the degree of CMV activity and the affection of the posterior pole of the eye as well as be sure of the elimination of the virus after end of treatment.