Comparability of two fundus photograph reading centers in grading cytomegalovirus retinitis progression

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Abstract

Purpose

To compare grading of cytomegalovirus retinitis progression by two different fundus photograph reading centers (FPRCs).

Design

Patients with AIDS followed in an ophthalmology service were enrolled in a prospective epidemiologic study of the prevalence and incidence of resistant cytomegalovirus in vitro.

Methods

We compared masked replicate gradings by two different FPRCs of monthly fundus photographs for retinitis progression (onset of a separate new lesion or expansion of an existing lesion by ≥one-half disk diameter).

Results

For 77 patients, Kaplan-Meier plots of progression over time were similar between FPRCs (median time to progression, 65 vs 69 days). Agreement between FPRCs was 51% (kappa [κ] = .37, “fair”) on exact visit of progression (28 patients) or on absence of progression through follow-up (11 patients) and 62% (κ = .38) on progression visit ± 1 month. Eight of 12 patients with progression graded as more than 1 month apart were only 2 months apart. Considering each monthly visit as a choice point, overall agreement on progression was 78% (κ = .55, “moderate”). Baseline evaluation of retinitis showed 95% agreement on presence/absence and a concordance correlation coefficient of .75 for extent in combined zones 1 and 2. Rates of retinal loss over follow-up were estimated as 2.8%/month vs 2.0%/month (P = .015).

Conclusions

By adopting similar protocols and procedures, different FPRCs can achieve good agreement on presence and extent of cytomegalovirus retinitis. Further efforts to harmonize evaluation through ongoing comparison of gradings would likely improve agreement on retinitis progression.

Section snippets

Patient selection

From the Johns Hopkins AIDS Ophthalmology Clinic, patients were enrolled who had newly diagnosed, active CMV retinitis, had received no prior treatment for CMV retinitis, had a diagnosis of AIDS, were age 18 years or older, and had received no treatment for extraocular CMV disease within the previous 28 days. The CRVR study was approved by the Johns Hopkins Hospital Joint Committee for Clinical Investigation before enrollment, and patients gave written, informed consent. Patients underwent a

Presence and location of CMV retinitis

Patients entering the study were required to have CMV retinitis involving at least one eye, based on clinical examination. In the sample of 77 patients (154 eyes) selected for comparison of results, the two FPRCs (designated FPRC A and FPRC B) both detected retinitis in at least one eye of all patients. To determine bilaterality of disease, however, individual eyes were considered. Among 154 eyes, agreement on presence/absence was 94.8% (present in 98 eyes and absent in 48 eyes). Of the 8 eyes

Discussion

Centralized assessment of CMV retinitis progression from standardized fundus photographs, employing one of several FPRCs, has been a widely used method of determining outcomes in various studies. Recognized benefits of using a central FPRC include: (1) standardization of assessment across multiple clinics; (2) masking of graders to patient characteristics other than retinal morphology (i.e., treatment assignment); (3) ability to test reproducibility of evaluations; and (4) opportunity to reduce

References (29)

  • D.A. Jabs et al.

    Cytomegalovirus retinitis and acquired immunodeficiency syndrome

    Arch Ophthalmol

    (1989)
  • C. Enger et al.

    Viral resistance and CMV retinitisDesign and methods for a prospective study

    Ophthalmic Epidemiol

    (1997)
  • G.N. Holland et al.

    A controlled retrospective study of ganciclovir treatment for cytomegalovirus retinopathyUse of a standardized system for the assessment of disease outcome

    Arch Ophthalmol

    (1989)
  • A.G. Palestine et al.

    A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS

    Ann Intern Med

    (1991)
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    This research was supported by Grant R01-EY-10268 from the National Eye Institute, National Institutes of Health, Bethesda, MD. Additional support was obtained from NEI grants K23 EY00386 (J.H.K.) and K24 E4004505 (D.A.J.). Dr. Jabs is the recipient of a Research to Prevent Blindness Senior Scientific Investigator Award. Dr. Jabs is a Research to Prevent Blindness Senior Scientific Investigator.

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