Retinal Degeneration in Choroideremia follows an Exponential Decay Function

Aylward, James; Xue, Kanmin; Patrício, Maria I.; Jolly, Jasleen K; Wood, Jonathan; Brett, Jonathan; Jasani, Kirti M; MacLaren, Robert E.

doi:10.1016/j.ophtha.2018.02.004

Cited by 33 publications

(60 citation statements)

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“…Four of these five patients were older and had later-stage disease. One patient was a young fast-progressor, as previously defined (Aylward et al 2018). The final patient that was excluded lacked both a smooth and mottled zone in the trans-foveal plane.…”

Section: Resultsmentioning

confidence: 98%

“…The FAF pattern, on the other hand, abruptly changes between smooth and mottled regions. The degeneration in choroideremia begins at the equator and then progresses centrally, but the photoreceptor density at the equator is less than in the central macula, which is in contrast to many macular dystrophies (Aylward et al 2018). The choroid, however, is thickest just under the fovea and becomes progressively thinner towards the equator, where it reaches less than a third of the central macular thickness (Margolis & Spaide 2009;Rasheed et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The rate of FAF loss is on average 7.7% of the residual area per year (Jolly et al 2016). This decay follows a logarithmic pattern, meaning that larger areas degenerate at a faster rate than smaller ones (Jolly et al 2016;Aylward et al 2018). Although retinal function is maintained over both the mottled and smooth regions, it is not yet known how these FAF changes predict the health of the overlying photoreceptors (Edwards et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors

Stevanovic

Cehajic-Kapetanovic

Jolly

et al. 2019

Acta Ophthalmologica

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Purpose: Choroideremia is an X-linked retinal disease characterized by early retinal pigment epithelium (RPE) loss and subsequent retinal degeneration. The RPE adopts either a smooth or mottled appearance on fundus autofluorescence (FAF). It is not known how RPE changes predict the health of the overlying ellipsoid zone (EZ). Methods: A retrospective review of FAF and optical coherence tomography (OCT) images from 20 patients with choroideremia was performed. The percentage of intact EZ in each smooth and mottled FAF region was determined using one horizontal trans-foveal OCT section. Results: Fourteen out of 20 patients had distinct smooth and mottled areas in both eyes and were included in the sub-analysis. On average, 62.5 AE 10.1% of the EZ in each smooth region of the right eyes was intact compared to 10.0 AE 4.3% in the mottled areas. The same trend was observed in left eyes: 76.5 AE 7.2% of the EZ was intact in the smooth regions versus 9.8 AE 3.9% in the mottled areas (two-way ANOVA, p < 0.0001). Thus, the mottled FAF regions were associated with EZ disruption more so than the smooth areas. Conclusion: Retinal pigment epithelium (RPE) changes correlate with the health of the overlying EZ in choroideremia. The smooth FAF region likely represents early stages of the disease, with most of the area containing preserved EZ, whereas the mottled zone indicates more advanced stages and has mostly disrupted EZ. Because of the clear relationship between FAF findings and EZ integrity, FAF imaging can be used to monitor disease progression and identify areas of preserved EZ that could be rescued by gene therapy.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors

Stevanovic

Cehajic-Kapetanovic

Jolly

et al. 2019

Acta Ophthalmologica

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“…18 Anatomical assessments included optical coherence tomography (OCT), which gives a crosssectional view and measurement of retinal thickness, 19 and blue-light autofluorescence, which generates a map that can be used to estimate the surviving retinal area. 20,21 It should however be noted that the eyes were not selected for anatomical symmetry and several eyes had residual retinal areas that had degenerated too much to be accurately measured. In choroideremia, the fovea is thickened early in the disease process before the onset of degeneration and it has been proposed that this is the result of glial cell activation resulting from retinal stress.…”

Section: Resultsmentioning

confidence: 99%

Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia

Xue

Jolly

Barnard

et al. 2018

Nat Med

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157

130

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Retinal gene therapy is increasingly recognised as a novel molecular intervention that has huge potential in treating common causes of blindness, the majority of which have a genetic aetiology. 1-5 Choroideremia is a chronic X-linked retinal degeneration that was first described in 1872. 6 It leads to progressive blindness due to deficiency of Rab-escort protein 1 (REP1). We designed an adenoassociated viral vector to express REP1 and assessed it in a gene therapy clinical trial by subretinal injection in 14 patients with choroideremia. The primary endpoint was vision change in treated eyes two years after surgery compared to unoperated fellow eyes. Despite complications in two patients, visual acuity improved in the 14 treated eyes over controls (median 4.5 letter gain, vs 1.5 letter loss, p=0.04), with six treated eyes gaining more than one line of vision (>5 letters). The results suggest that retinal gene therapy can sustain and improve visual acuity in a cohort of predominantly late stage choroideremia patients in whom rapid visual acuity loss would ordinarily be predicted.

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“…Diese Progression kann sowohl funktionell (Perimetrie) als auch strukturell (Fundusautofluoreszenz oder OCT) im Verlauf beobachtet werden. Zur Beschreibung der assoziierten Flächenverlustrate sind sowohl exponentielle als auch lineare Modelle vorgeschlagen worden [55,58,59]. Für einen exponentiellen Verlauf spricht, dass ein konstantes radiales Voranschreiten eine quadratische Metrik des Flächenverlustes bedingen sollte [55], wie sie auch für andere Netzhautdegenerationen vorbeschrieben ist [60 -64].…”

Section: Frühphaseunclassified

Der natürliche Verlauf der Choroideremie

Seitz

Fischer

2019

Klin Monatsbl Augenheilkd

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ZusammenfassungSeit ihrer Erstbeschreibung im Jahr 1872 herrscht um den natürlichen Verlauf der Choroideremie eine rege und in Teilen bis heute andauernde akademische Debatte. Aufgrund der Seltenheit der Erkrankung verlief diese traditionell weitgehend am Rande des klinisch geprägten Interessenhorizonts. Nun jedoch hat die Entwicklung grundlegend neuer, potenziell verlaufsmodifizierender Therapieansätze die Frage nach dem natürlichen Verlauf der Chorioideremie ins Zentrum der Aufmerksamkeit eines größeren Fachpublikums gerückt. Dieser Übersichtsartikel subsumiert den aktuellen Stand der Fachliteratur zum natürlichen Verlauf dieser seltenen Erkrankung und illustriert dessen Eigenheiten anhand eines übersichtlichen 2-Phasen-Modells. Neben einer ausführlichen Besprechung klinisch gängiger Modalitäten liegt der Fokus des Manuskripts auf der Ausarbeitung forschungsrelevanter Fragestellungen wie der intraindividuellen Symmetrie sowie der Etablierung neuer Endpunkte. Darüber hinaus werden die Limitationen bisheriger Studien diskutiert und Empfehlungen für zukünftige Beobachtungsstudien entwickelt.

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Retinal Degeneration in Choroideremia follows an Exponential Decay Function

Cited by 33 publications

References 5 publications

A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors

A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors

Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia

Der natürliche Verlauf der Choroideremie

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