Ocular Complications of HIV/AIDS in the Era of HAART

Millena G Bittencourt; Owhofasa O Agbedia; Hong T Liu; Rachel Annam; Yasir J Sepah; Henry Alexander Leder; Raafay Sophie; Mohamed Ibrahim; Abeer Akhtar; Anam Akhlaq; Diana V Do; Quan Dong Nguyen

Disclosures

Expert Rev Ophthalmol. 2012;7(6):555-564. 

In This Article

Immune Recovery Uveitis

Immune recovery uveitis (IRU) is part of the immune reconstitution inflammatory syndrome, which has been described in other organs and with other opportunistic infections (such as mycobacterium infections).[1] IRU, also known as immune recovery vitritis, is a relatively new HIV-related eye disease, which was first described in 1998 to be a consequence of rapid immune reconstitution after the use of HAART among patients with HIV infection.[61,83]

The AIDS Clinical Trial Group defined IRU as a 'decrease in vision and at least two of the following signs in the absence of active CMVR: presence of >2+ inflammatory cells in vitreous by slit lamp examination, cystoid macular edema (CME) or epiretinal membrane formation in patients receiving potent antiretroviral therapy with evidence of immune reconstitution'.[84] Immune reconstitution, in its turn, was defined as 100 cells/mm3 or more. Another definition of IRU by the NIH sponsored Studies of the Ocular Complications of AIDS is 'the occurrence of intermediate uveitis in patients with CMVR who have evidence of immune reconstitution, as shown by a rise in CD4 T-cell counts after the initiation of HAART'.[84]

There is a wide variation in the incidence of IRU. Lai and colleagues reported the incidence of IRU to be 1% in 105 patients who were followed up for 6 months, although their study included a higher proportion of patients with visual loss.[85] Lin and colleagues reported the incidence of IRU to be 24.4% among HAART responders.[86] In a similar study by Nguyen and colleagues, IRU occurred at a substantially lower rate (0.109/PY) among patients who responded to HAART compared with 0.83/PY, which was observed in a similar study conducted by Karavellas and colleagues.[87,88]

IRU has become one of the leading causes of severe vision impairment in patients with CMVR.[89] The incidence of visual impairment among patients with IRU is 0.17 case/EY.[25,26] Despite the increasing number of IRU cases, the mechanism by which the disease occurs is poorly understood; the full spectrum of clinical features, including the rates of complications, the course of disease and visual outcomes are yet to be described. It has been postulated that IRU may be caused by an immune response against a persistent CMV antigen in the eye. A histopathologic study of treated CMVR demonstrated the presence of viral DNA at the border of the lesion but ineffective assembly of intact virions.[23] CMVR causes a breakdown in the blood–ocular barrier and may allow migration of inflammatory cells into the eye, thereby promoting the sensitization to CMV antigens and favoring the development of an IRU.[90] It was hypothesized that IRU would be more frequent in patients receiving HAART therapy with partial recovery of immune system than in patients with full recovery. The hypothesis is based on the incidence of 0.83 to 0.11/PY in patients with partial recovery and the incidence of 0.04/PY in patients with full recovery of immune system.[1]

The primary risk factors for IRU are extent of retinitis and a history of treatment with cidofovir. Retinitis occupying more than 30% of retinal area confers a relative risk for IRU of 4.5 compared with those eyes with less than 18% retinal area involvement.[61] Treatment with cidofovir is associated with the odds of developing IRU being 3.3 times greater compared with an alternative regimen and 5.2 times greater when compared with an untreated case.[91]

Mild or absent anterior chamber and vitreous cellular response is seen in patients with immune compromised CMVR. By contrast, new and severe vitritis and increase in the anterior chamber inflammatory reaction is seen in patients with IRU after the introduction of HAART. Patients with IRU may also have optic disc edema, macular edema and epiretinal membrane formation. Complications of inflammation such as vitreomacular traction and retina neovascularization have also been reported.[92,93]

To date, corticosteroids, systemic and local, have been the most common treatment for IRU. The role of prolonged and aggressive anti-CMV therapy after the initiation of HAART to reduce the rate or severity of IRU deserves further investigation. Periocular, intravitreal and oral corticosteroids have been used in small case series with an overall success rate of about 50%.[57,87,94] The use of a fluocinolone acetonide implant (RETISERT®, Bausch and Lomb, NY, USA) along with maintenance anti-CMV therapy to treat persistent CME has been described in a case series. Hu and colleagues described two cases in which CME resistant to local and systemic corticosteroid therapy was treated with combinations of a Retisert implant and systemic valaciclovir or ganciclovir implant with a mean follow-up period of 5 months.[95] In their case series, the CD4 cell count was at least 3 times the limit of 100 cells/mm3 as stated for immune recovery; the CMV load was undetectable. A long period without CMV reactivation was observed and there were no clinical signs of CMVR.

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