Dataset Information

Histologic basis of variations in retinal pigment epithelium autofluorescence in eyes with geographic atrophy.

ABSTRACT:

Purpose

Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression.

Design

Experimental study.

Participants and controls

Ten GA donor eyes (mean age ± standard deviation, 87.1 ± 4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0 ± 7.2 years) without GA.

Methods

The 10-micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch's membrane at 0.2-?m intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF]).

Main outcome measures

Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes.

Results

The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades.

Conclusions

Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin.

SUBMITTER: Rudolf M

PROVIDER: S-EPMC3633595 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Histologic basis of variations in retinal pigment epithelium autofluorescence in eyes with geographic atrophy.

Rudolf Martin M Vogt Susan D SD Curcio Christine A CA Huisingh Carrie C McGwin Gerald G Wagner Anna A Grisanti Salvatore S Read Russell W RW

Ophthalmology 20130126 4

<h4>Purpose</h4>Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression.<h4>Design</h4>Experimental study.<h4>Participants and controls</h4>Ten GA donor eyes (mea ...[more]

PMID: 23357621

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Project description:PurposeTo evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF).MethodsRetrospective cohort study of patients with STGD1 with ≥2 gradable SW-FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models.ResultsFifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10-0.85) mm2/year on SW-FAF and 0.24 (0.08-0.33) mm2/year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm2/year, P < 0.001), worse visual acuity (0.305 mm2/year, P = 0.005), multifocal disease (0.401 mm2/year, P = 0.02), and SW-FAF pattern (0.534 mm2/year, P =0 .03) were associated with a faster rate of progression (predictive R 2: 0.65).ConclusionsSW-FAF and NIR-FAF are not interchangeable in the evaluation of RPE-atrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression.Translational relevanceThe knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design.

Project description:ObjectiveTo image healthy retinal pigment epithelial (RPE) cells in vivo using Transscleral OPtical Imaging (TOPI) and to analyze statistics of RPE cell features as a function of age, axial length (AL), and eccentricity.DesignSingle-center, exploratory, prospective, and descriptive clinical study.ParticipantsForty-nine eyes (AL: 24.03 ± 0.93 mm; range: 21.9-26.7 mm) from 29 participants aged 21 to 70 years (37.1 ± 13.3 years; 19 men, 10 women).MethodsRetinal images, including fundus photography and spectral-domain OCT, AL, and refractive error measurements were collected at baseline. For each eye, 6 high-resolution RPE images were acquired using TOPI at different locations, one of them being imaged 5 times to evaluate the repeatability of the method. Follow-up ophthalmic examination was repeated 1 to 3 weeks after TOPI to assess safety. Retinal pigment epithelial images were analyzed with a custom automated software to extract cell parameters. Statistical analysis of the selected high-contrast images included calculation of coefficient of variation (CoV) for each feature at each repetition and Spearman and Mann-Whitney tests to investigate the relationship between cell features and eye and subject characteristics.Main outcome measuresRetinal pigment epithelial cell features: density, area, center-to-center spacing, number of neighbors, circularity, elongation, solidity, and border distance CoV.ResultsMacular RPE cell features were extracted from TOPI images at an eccentricity of 1.6° to 16.3° from the fovea. For each feature, the mean CoV was < 4%. Spearman test showed correlation within RPE cell features. In the perifovea, the region in which images were selected for all participants, longer AL significantly correlated with decreased RPE cell density (R Spearman, Rs = -0.746; P < 0.0001) and increased cell area (Rs = 0.668; P < 0.0001), without morphologic changes. Aging was also significantly correlated with decreased RPE density (Rs = -0.391; P = 0.036) and increased cell area (Rs = 0.454; P = 0.013). Lower circular, less symmetric, more elongated, and larger cells were observed in those > 50 years.ConclusionsThe TOPI technology imaged RPE cells in vivo with a repeatability of < 4% for the CoV and was used to analyze the influence of physiologic factors on RPE cell morphometry in the perifovea of healthy volunteers.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Dataset Information

Histologic basis of variations in retinal pigment epithelium autofluorescence in eyes with geographic atrophy.

Purpose

Design

Participants and controls

Methods

Main outcome measures

Results

Conclusions

Publications

Histologic basis of variations in retinal pigment epithelium autofluorescence in eyes with geographic atrophy.

Similar Datasets

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