Cytomegalovirus retinitis in the post-cART era

Abstract

Purpose of review: To review the epidemiology, diagnosis, and management of cytomegalovirus retinitis (CMVR) in the post-combined antiretroviral era (cART) era.

Recent findings: Although cART has dramatically reduced CMVR incidence and morbidity in the HIV population, CMVR continues to cause significant vision loss in both HIV and non-HIV patients, especially amongst patients without immune reconstitution. Advances in imaging including ultra-widefield fundus and autofluorescence imaging, optical coherence tomography, and adaptive optics may reflect CMVR activity; however, the diagnosis remains a clinical one. There have been minimal advances in therapy, with several agents no longer available due to market concerns.

Summary: Despite reduced incidence and morbidity in the post-cART HIV population, CMVR continues to cause vision loss amongst HIV and non-HIV patients. Diagnosis remains primarily clinical, and therapy centers upon immune reconstitution along with systemic and/or intravitreal antivirals. Further studies are necessary to determine whether advanced imaging can influence management, and whether novel antiviral agents or adoptive immune transfer have a role in treatment of drug-resistance CMVR.

Keywords: HAART; cART; cytomegalovirus retinitis.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 1:. Clinical and imaging findings in cytomegalovirus (CMV) retinitis

(A) Ultra-widefield fundus photograph of hemorrhagic CMV retinitis with “brush-fire” pattern demonstrates areas of retinal whitening and necrosis along with overlying hemorrhage. Retinitis typically occurs along the vascular arcades and progresses centripetally towards the posterior pole. (B) Ultra-widefield fundus photograph of granular CMV retinitis demonstrates granular, hypopigmented lesions with only rare retinal hemorrhages. There are also a few faint, punctate hypopigmented lesions along the arcades. (C) Ultra-widefield fundus photograph demonstrating recurrent CMV retinitis, as noted by whitening, at the edge of the nasal chorioretinal atrophy from prior CMV retinitis and superiorly. (D) FAF imaging of the same eye at the same time showed stippled hyper- and hypo-autofluorescence in the area of healed CMV retinitis car, with a hyper-autofluorescent border in the area of reactivation as well as in the new area of retinitis superiorly. (E) Ultra-widefield fundus photograph demonstrating retinitis and whitening with numerous retinal breaks and associated rhegmatogenous retinal detachment inferonasally. (F) After repair with pars plana vitrectomy with silicone oil, the retina is attached with laser scars and CMV scars noted.

Figure 2:. Ellipsoid zone (EZ) disruption in cytomegalovirus (CMV) retinitis

Spectral domain-optical coherence tomography (SD-OCT) through areas of active CMV retinitis demonstrate retinal architecture disruption with hyperreflectivity and disruption of the EZ (A). The Heidelberg viewing system marker (green line, A-B) is used to denote the border of normal and disrupted EZ at the edge of one retinitis lesion presentation. After one week (B), EZ disruption is noted to progress to the left side of the marker, in an area of previously intact EZ (A). After escalation of antiviral therapy and control of CMV retinitis, no further progression of EZ disruption is noted from this same time point (shown again in C) until 3 months later (D). The area to the right of the Heidelberg viewing system marker (green line, C-D), which had shown EZ disruption (C), shows progressive worsening of retinal architecture with retinal thinning over the same time period (D). The area to the left of the marker shows stable intact retinal architecture and EZ (C-D).