A Workshop on Measuring the Progression of Atrophy Secondary to Stargardt Disease in the ProgStar Studies: Findings and Lessons Learned

Ervin, Ann‐Margret; Strauss, Rupert W.; Ahmed, Mohamed; Birch, David G.; Cheetham, Janet K; Ferris, Frederick L.; Ip, Michael S.; Jaffe, Glenn J.; Maguire, Maureen G.; Schönbach, Etienne M; Sadda, Srinivas R; West, Sheila K.; Scholl, Hendrik P. N.

doi:10.1167/tvst.8.2.16

Cited by 31 publications

(28 citation statements)

References 40 publications

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“…Indeed, two different types of decreased autofluorescence have been proposed based on the measurement of relative of darkness with respect to the optic nerve head (or, if not present in the image, the retinal vessels), considered as the reference for 100% blackness on the gray scale: definitely decreased autofluorescence (DDAF), defined as a signal more than 90% black in reference to the optic nerve head, and questionably decreased autofluorescence (QDAF), defined as 50% to 90% black, as compared to the reference 53. Areas of QDAF tend to be unstable on consecutive examinations; they have been interpreted as a transition state between healthy retina and regions of advanced disease (ie, DDAF).…”

Section: Monitoring Progression Of Stgd1mentioning

confidence: 99%

<p>Monitoring and Management of the Patient with Stargardt Disease</p>

Cicinelli¹,

Battista²,

Starace³

et al. 2019

OPTO

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Stargardt disease (STGD1) represents one of the major common causes of inherited irreversible visual loss. Due to its high phenotypic and genotypic heterogeneity, STGD1 is a complex disease to understand. Non-invasive imaging, biochemical, and genetic advances have led to substantial improvements in unveiling the disease processes and novel promising therapeutic landscapes have been proposed. This review recapitulates the modalities for monitoring patients with STGD1 and the therapeutic options currently under investigation for the different stages of the disease.

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Section: Monitoring Progression Of Stgd1mentioning

confidence: 99%

<p>Monitoring and Management of the Patient with Stargardt Disease</p>

Cicinelli¹,

Battista²,

Starace³

et al. 2019

OPTO

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“…The clinical course of STGD1 is heterogeneous, and little is known about factors predicting the natural history of the disease. 3 , 4 The anticipation of patients with a faster rate of RPE-atrophy enlargement may be important in both clinical practice and research. The choice of the strategies and endpoints in therapeutic interventional trials may be different according to the predictive characteristics of each patient.…”

Section: Introductionmentioning

confidence: 99%

Factors Influencing Retinal Pigment Epithelium-Atrophy Progression Rate in Stargardt Disease

Cicinelli

Rabiolo

Brambati

et al. 2020

Trans. Vis. Sci. Tech.

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To 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). Methods: Retrospective 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. Results: Fifty-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) mm 2 /year on SW-FAF and 0.24 (0.08-0.33) mm 2 /year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm 2 /year, P < 0.001), worse visual acuity (0.305 mm 2 /year, P = 0.005), multifocal disease (0.401 mm 2 /year, P = 0.02), and SW-FAF pattern (0.534 mm 2 /year, P =0 .03) were associated with a faster rate of progression (predictive R 2 : 0.65). Conclusions: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPEatrophy 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 Relevance: The 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.

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“…For example, the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study group previously demonstrated good reproducibility of total retinal, EZ, and ONL thickness measurements on SD-OCT in a small subset (30 patients) of patients as part of a prospective natural history study 31 . However, numerous challenges to segmentation were encountered, including difficulty identifying boundaries for pathologic areas of layer disruption and algorithm failures that required tedious (6-8 h per eye) manual segmentation 32 . Our results demonstrate that OCT-based analysis of individual retinal sublayer thicknesses is feasible for the majority of Stargardt patients seen in an inherited retinal disease clinic.…”

Section: Discussionmentioning

confidence: 99%

“…Detection of photoreceptor and RPE loss in STGD1 are method-dependent, and most of the previously-published work has used en face imaging using short-wavelength autofluorescence (SW-AF) or near-infrared autofluorescence (NIR-AF). These methods analyze disease progression by tracking area of involvement but require atrophic loss of RPE cells to measure a discrete, hypo-autofluorescent border, which can sometimes be difficult to distinguish (e.g., determination of disease borders on SW-AF can be challenging due to accumulation of hyper-autofluorescent material in photoreceptor cells) 32 . Studies using en face SW-AF or NIR-AF imaging have suggested that the rate of RPE loss correlates with EZ loss, particularly when the total area of abnormal autofluorescence (hypo- and hyper-autofluorescence) are considered using SW-AF; however, using NIR-AF, RPE atrophy appears to precede detectable photoreceptor loss 11 , 14 , 45 – 47 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of retinal sublayer thicknesses and rates of change in ABCA4-associated Stargardt disease

Whitmore

Fortenbach

Cheng

et al. 2020

Sci Rep

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Stargardt disease, the most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy. Although clinical trials for Stargardt are currently underway, the disease is typically slowly progressive, and objective, imaging-based biomarkers are critically needed. In this retrospective, observational study, we characterize the thicknesses of individual retinal sublayers by macular optical coherence tomography (OCT) in a large cohort of patients with molecularly-confirmed, ABCA4-associated Stargardt disease (STGD1) relative to normal controls. Automated segmentation of retinal sublayers was performed with manual correction as needed, and thicknesses in various macular regions were compared using mixed effects models. Relative to controls (42 eyes, 40 patients), STGD1 patients (107 eyes, 63 patients) had slight thickening of the nerve fiber layer and retinal pigment epithelium-Bruch’s membrane, with thinning in other sublayers, especially the outer nuclear layer (ONL) (p < 0.0015). When comparing the rate of retinal sublayer thickness change over time (mean follow-up 3.9 years for STGD1, 2.5 years for controls), STGD1 retinas thinned faster than controls in the outer retina (ONL to photoreceptor outer segments). OCT-based retinal sublayer thickness measurements are feasible in STGD1 patients and may provide objective measures of disease progression or treatment response.

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A Workshop on Measuring the Progression of Atrophy Secondary to Stargardt Disease in the ProgStar Studies: Findings and Lessons Learned

Cited by 31 publications

References 40 publications

<p>Monitoring and Management of the Patient with Stargardt Disease</p>

<p>Monitoring and Management of the Patient with Stargardt Disease</p>

Factors Influencing Retinal Pigment Epithelium-Atrophy Progression Rate in Stargardt Disease

Analysis of retinal sublayer thicknesses and rates of change in ABCA4-associated Stargardt disease

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