Cytomegalovirus Retinitis

Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomegalovirus, can manipulate expression of these host proteins, with overstimulation of SOCS1 and/or SOCS3 putatively facilitating viral evasion of immune surveillance, and SOCS suppression generally exacerbating immunopathogenesis. This is particularly poignant within the eye, which contains a diverse assortment of specialized cell types working together in a tightly controlled microenvironment of immune privilege. When the immune privilege of the ocular compartment fails, inflammation causing severe immunopathogenesis and permanent, sight-threatening damage may occur, as in the case of AIDS-related human cytomegalovirus (HCMV) retinitis. Herein we review how SOCS1 and SOCS3 impact the virologic, immunologic, and/or pathologic outcomes of herpesvirus infection with particular emphasis on retinitis caused by HCMV or its mouse model experimental counterpart, murine cytomegalovirus (MCMV). The accumulated data suggests that SOCS1 and/or SOCS3 can differentially affect the severity of viral diseases in a highly cell-type-specific manner, reflecting the diversity and complexity of herpesvirus infection and the ocular compartment.

BackgroundCytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 MethodsThis is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 ResultsA total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered.ConclusionsA strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections.

Ganciclovir (GCV) is one of the most widely used antiviral drugs for the treatment of cytomegalovirus (CMV) retinitis. In this context, the aim of this study was to design in situ thermosensitive hydrogels for GCV ocular delivery by intravitreal injection to achieve sustained drug release behavior and improved ocular bioavailability in the treatment of CMV retinitis. A thermosensitive poly-(β-butyrolactone-co-lactic acid)-polyethylene glycol-poly (β-butyrolactone-co-lactic acid) (PBLA-PEG-PBLA) triblock copolymer was synthesized by ring-opening polymerization and characterization. The GCV-loaded PBLA-PEG-PBLA in situ hydrogels (15%, w/w) were then prepared with drug concentration at 2 mg·mL-1 and the gelation temperatures, rheological properties, in vitro degradation and syringeability of in situ hydrogels for intravitreal injection were also investigated. Membraneless dissolution model was used to explore drug release behavior of PBLA-PEG-PBLA in situ hydrogel. The results indicated that more than 45 and 85% of GCV can be released within 24 and 96 h, respectively, which was verified by a non-Fickian diffusion mechanism. In vivo ocular pharmacokinetics study showed that area under drug-time curve (AUC) and half-life of PBLA-PEG-PBLA in situ hydrogel was higher (AUC was 61.80 μg·mL-1·h (p 1/2 was 10.29 h in aqueous humor; AUC was 1008.66 μg·mL-1·h (p 1/2 was 13.26 h (p < .01) in vitreous) than GCV injection with extended therapeutic activity. Based on obtained results, it was concluded that the thermosenstive PBLA-PEG-PBLA in situ hydrogel is a promising carrier of GCV for intravitreal injection.

BackgroundCytomegalovirus (CMV) retinitis has been increasingly reported in patients receiving Janus kinase (JAK) inhibitors, yet vision-threatening ischemic complications in this population remain poorly characterized. Immune recovery uveitis (IRU) and cystoid macular edema (CME) are recognized post-infectious sequelae, but delayed retinal ischemia and hemorrhage in the setting of JAK inhibition are uncommon. We present a case that illustrates these complications in a patient on upadacitinib for rheumatoid arthritis.Case presentationAn 81-year-old woman with rheumatoid arthritis on upadacitinib for approximately one year and long-term hydroxychloroquine presented with decreased vision and floaters in her left eye. Examination revealed vitritis, focal hemorrhagic retinitis, and an epiretinal membrane without CME. Anterior chamber paracentesis confirmed CMV infection via aqueous humor polymerase chain reaction, guiding prompt antiviral therapy. She received oral valganciclovir and alternating intravitreal ganciclovir and foscarnet, though systemic therapy was later discontinued due to leukopenia. After cessation of upadacitinib and hydroxychloroquine, the retinitis stabilized, but she developed IRU with new-onset CME. Weeks later, she presented with a dense vitreous hemorrhage without retinal tears or detachment. Fluorescein angiography revealed temporal retinal ischemia remote from the original retinitis. Intravitreal bevacizumab led to improvement in both CME and hemorrhage. Pan-retinal photocoagulation is planned to reduce the risk of recurrent hemorrhage.ConclusionsThis case illustrates CMV retinitis in the setting of JAK inhibition complicated by delayed retinal ischemia and vitreous hemorrhage arising remote from the original retinitis. Although ischemic vasculopathy is a recognized complication of CMV retinitis among non-HIV immunosuppressed patients, such sequelae have been infrequently documented in JAK inhibitor-associated cases. Ophthalmologists should maintain a high index of suspicion for CMV retinitis in this emerging population and continue close surveillance for delayed ischemic complications even after apparent disease stabilization.