Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS

Abstract

Purpose: To evaluate risk factors for severity of cytomegalovirus (CMV) retinitis lesion whitening (opacity), using a standardized scoring system.

Methods: We performed a cross-sectional, observational investigation of all individuals with newly diagnosed AIDS-related CMV retinitis in three randomized clinical trials and one prospective observational study. Opacity was scored by masked readers, using a prospectively defined ordinal 6-point scale. Demographic factors, laboratory data (CD4+, CD8+ T-lymphocyte counts, human immunodeficiency virus [HIV] blood levels), and lesion characteristics (location, size) were compared to the highest opacity score assigned to either eye. Among eyes with active lesions (scores ≥3), factors associated with severe opacity (scores 5, 6) were identified.

Results: There were 299 participants (401 eyes with CMV retinitis). In one or more comparisons, increased opacity was associated with lower CD4+ and lower CD8+ T-lymphocyte counts, higher HIV blood level, lack of antiretroviral therapy, male sex, race/ethnicity, and bilateral disease. In eyes with active disease, severe opacity was associated with lower CD4+ T-lymphocyte count, higher HIV blood level, older age, Karnofsky score, lesion size, and bilateral disease. No relationship was identified between opacity and lesion location.

Conclusions: Lesion border opacity (resulting from CMV activity) reflects level of immune function; as immunodeficiency becomes worse, CMV activity (and opacity) increases. The positive relationship between opacity and HIV blood level may reflect both immunodeficiency and increased CMV activity caused by transactivation of CMV by HIV. Scoring of opacity may be a useful, standard measure for continued study of CMV retinitis across different settings and populations. (Clinicaltrials.gov number for the HPMPC CMV Retinitis Trial: NCT00000142; Clinicaltrials.gov number for the Monoclonal Antibody CMV Retinitis Trial: NCT00000135; Clinicaltrials.gov number for the Ganciclovir-Cidofovir CMV Retinitis Trial: NCT0000014; Clinicaltrials.gov number for the Longitudinal Study of the Ocular Complications of AIDS: NCT00000168.).

Trial registration: ClinicalTrials.gov NCT00000142 NCT00000135 NCT00000014 NCT00000168.

Figures

Figure

Standard photographs used for scoring CMV retinitis lesion border opacity. Grade 1 is assigned to inactive atrophic scars (standard photograph 1, first row, left). Grade 2 is assigned to lesions with questionable or equivocal lesion opacity (standard photograph 2, first row, middle). Grade 3 is assigned to mild opacity (equivalent to or exceeding the opacity of standard photograph 3, first row, right, but less than standard photographs 4A–C, second row). Grade 4 is assigned to moderate opacity (equivalent to or exceeding the opacity of standard photographs 4A–C, but less than standard photographs 5A–C, third row). Grade 5 is assigned to severe opacity (equivalent to or exceeding the opacity of standard photographs 5A–C, but less than standard photographs 6A–C, fourth row). Grade 6 is assigned to very severe opacity (equivalent to or exceeding the opacity of standard photographs 6A–C. Lesions assigned grades 3 through 6 are considered to be active.