Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Strauss, Rupert W.; Kong, Xiangrong; Muñoz, Beatriz; Ibrahim, Mohamed; Sunness, Janet S.; Hahn, Gesa-Astrid; Nasser, Fadi; Zrenner, Eberhart; Scholl, Hendrik P. N.; Wolfson, Yulia; Bittencourt, Millena; Shah, Syed Mahmood; Ahmed, Mohamed; Schönbach, Etienne M; Fujinami, Kaoru; Traboulsi, Elias I.; Ehlers, Justis P.; Marino, Meghan J; Crowe, Susan; Briggs, Rachael; Borer, Angela; Pinter, Anne; Fecko, Tami; Burgnoni, Nikki; Applegate, Carol A.; Russell, Leslie; Michaelides, Michel; Esposti, Simona Degli; Moore, Anthony T.; Webster, Andrew R.; Connor, Sophie; Barnfield, Jade; Salchi, Zaid; Alfageme, Clara; McCudden, Victoria; Pefkianaki, Maria; Aboshiha, Jonathan; Liew, Gerald; Holder, Graham E.; Robson, Anthony G.; King, Alexa; Narvaez, Daniela Ivanova Cajas; Barnard, Katy; Grigg, Catherine; Dunbar, Hannah; Obadeyi, Yetunde; Girard-Claudon, Karine; Swann, Hilary; Rughani, Avani; Amoah, Charles; Carrington, Dominic; Bibi, Kanom; Co, Emerson Ting; Illiyas, Mohamed Nafaz; Begum, Hamida; Carter, Andrew; Georgiou, Anne; Lewism, Selma; Shaheen, Saddaf; Shinmar, Harpreet; Burton, Linda M.; Bernstein, Paul S.; Wegner, Kimberley; Sawyer, Briana Lauren; Carlstrom, Bonnie; Farnsworth, Kellian; Fry, Cyrie; Chandler, Melissa; Jenkins, Glen; Creel, Donnel; Birch, David G.; Wang, Yizhong; Rodriguez, Luis; Locke, Kirsten; Klein, Martin; Mejia, Paulina; Cideciyan, Artur V.; Jacobson, Samuel G.; Schwartz, Sharon; Matsui, Rodrigo; Gruzensky, Michaela; Charng, Jason; Román, Alejandro J.; Hahn, Gesa Astrid; Wilhelm, Barbara; Peters, Tobias; Beier, Benjamin; Koenig, Tilman; Krämer, Susanne; Sahel, José‐Alain; Mohand‐Saïd, Saddek; Audo, Isabelle; Laurent-Coriat, Caroline; Sliesoraitytė, Ieva; Zeitz, Christina; Boyard, Fiona; Tran, Minh Ha; Chapon, Mathias; Chaumette, Céline; Amaudruz, Juliette; Ganem, Victoria J.; Sancho, Serge; Girmens, Aurore; Wojciechowski, Robert; Khan, Shazia; Emmert, David; Cain, Dennis; Herring, Mark; Bassinger, Jennifer; Liberto, Lisa; West, Sheila K.; Ervin, Ann‐Margret; Dreger, Kurt; Jones, Jennifer; Sadda, Srinivas R; Ip, Michael S.; Jha, Anamika; Ho, Alex; Kramer, Brendan; Lam, Ngoc; Tawdros, Rita; Zhou, Yong Dong; Carmona, Johana; Uji, Akihito; Hariri, Amirhossein; Lock, Amy; Elshafei, Anthony; Ganegoda, Anushika; Petrossian, Christine; Jenkins, Dennis; Strnad, Edward; Baghdasaryan, Elmira; Ito, Eric; Samson, Feliz; Blanquel, Gloria; Akıl, Handan; Melendez, Jhanisus; Lei, Jianqin; Huang, Jianyan; Chau, Jonathan; Falavarjani, Khalil Ghasemi; Espino, Kristina; Li, Manfred; Mendoza, Maria A.; Nittala, Muneeswar Gupta; Roded, Netali; Saleh, Nizar; Huang, Ping; Pitetta, Sean; Balasubramanian, Siva; Leahy, Sophie; Srinivas, Sowmya; Velaga, Swetha Bindu; Margaryan, Teresa; Tepelus, Tudor; Brown, Tyler; Fan, Wenying; Murillo, Yamileth; Shi, Yue; Aguilar, Katherine Elizabeth Gonzaga; Chan, Cynthia; Santos, Lisa; Seo, Brian; Sison, Christopher; Pérez, Silvia; Chao, Stephanie; Miyasato, Kelly; Higgins, Julia; Luna, Zoila; Menchaca, Anita; Gonzalez, Norma; Robledo, Vicky; Carig, Karen; Baker, Kirstie; Ellenbogen, David; Bluemel, Daniel; Sanford, Theo; Linares, Daisy; Tran, Mei; Nava, Lorane; Oberoi, Michelle K.; Romero, Mark; Chiguil, Vivian; Bynum-Bain, Grantley; Kim, Monica; Mendiguren, Carolina; Huang, Xiwen; Smith, Monika; Sarreal, Natalie

doi:10.1016/j.ajo.2018.06.003

Cited by 26 publications

(18 citation statements)

References 30 publications

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“…Numerous systematic protocols have been developed and this is the standard used by all clinical trials ( Table 6 ). Many studies have documented broad trends in BCVA progression and its relationship to other clinical features in ABCA4 -associated retinopathy ( Birch et al, 2001 ; Collison and Fishman, 2018 ; Ergun et al, 2005 ; Kong et al, 2016 ; Parodi et al, 2015 ; Querques et al, 2008 ; Testa et al, 2012 , 2014 ), however as a method, it is perhaps most susceptible to technical limitations such as measurement bias, repeatability as well as confounders that are specific to ABCA4 -associated retinopathy such as the variable status of the fovea ( Bax et al, 2019b ; Collison et al, 2019 ; Nakao et al., 2012 ; van Huet et al, 2014 ) and shifting of the preferred retinal locus (PRL) into consideration ( Bethlehem et al, 2014 ; Greenstein et al, 2008 ; Krishnan and Bedell, 2018 ; Schonbach et al, 2017a , 2018 ).…”

Section: Clinical Outcome Measuresmentioning

confidence: 99%

Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations

Cremers

Lee

Collin

et al. 2020

Progress in Retinal and Eye Research

216

227

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The ABCA4 protein (then called a “rim protein”) was first identified in 1978 in the rims and incisures of rod photoreceptors. The corresponding gene, ABCA4 , was cloned in 1997, and variants were identified as the cause of autosomal recessive Stargardt disease (STGD1). Over the next two decades, variation in ABCA4 has been attributed to phenotypes other than the classically defined STGD1 or fundus flavimaculatus, ranging from early onset and fast progressing cone-rod dystrophy and retinitis pigmentosa-like phenotypes to very late onset cases of mostly mild disease sometimes resembling, and confused with, age-related macular degeneration. Similarly, analysis of the ABCA4 locus uncovered a trove of genetic information, including >1200 disease-causing mutations of varying severity, and of all types – missense, nonsense, small deletions/insertions, and splicing affecting variants, of which many are located deep-intronic. Altogether, this has greatly expanded our understanding of complexity not only of the diseases caused by ABCA4 mutations, but of all Mendelian diseases in general. This review provides an in depth assessment of the cumulative knowledge of ABCA4-associated retinopathy – clinical manifestations, genetic complexity, pathophysiology as well as current and proposed therapeutic approaches.

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Section: Clinical Outcome Measuresmentioning

confidence: 99%

Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations

Cremers

Lee

Collin

et al. 2020

Progress in Retinal and Eye Research

216

227

View full text Add to dashboard Cite

show abstract

“…Numerous clinical trials of gene therapy and stem cell therapy for Stargardt disease are currently underway, and inclusion of easily-acquired, objective measures of disease progression or treatment response remain critically needed 50 – 54 . Due to the relatively slow progression of STGD1 and the variability in foveal involvement, it is difficult to follow disease progression in clinical trials using best-corrected visual acuity 55 , and measurements are sometimes limited by ability to fixate and by changes in fixation location 56 . Other tests such as Goldmann visual fields are time-consuming and subjective, while electroretinography is also technically challenging in some patients with relatively low test repeatability, limiting its ability to detect small changes over time.…”

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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“…The overall mean sensitivity decreased in the cohort over 24 months, but the data are very heterogeneous with eyes with improved sensitivity. Pattern placement and use of Nidek's follow-up function only in part of the population were considered additional reasons for differences seen in the mean sensitivity data, but the change in mean sensitivity did not differ by use of the follow-up function at 1 year 32. Similarly the change in mean sensitivity of eyes with good or fair pattern placement at baseline and 12 months did not differ from the change in mean sensitivity among eyes with pattern placement graded as poor during at least one visit 32…”

Section: Microperimetrymentioning

confidence: 99%

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

Ervin

Strauss

Ahmed

et al. 2019

Trans. Vis. Sci. Tech.

Self Cite

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The Progression of Atrophy Secondary to Stargardt Disease (ProgStar) studies were designed to measure the progression of Stargardt disease through the use of fundus autofluorescence imaging, optical coherence tomography, and microperimetry. The overarching objectives of the studies were to document the natural course of Stargardt disease and identify the most appropriate clinical outcome measures for clinical trials assessing the efficacy and safety of upcoming treatments for Stargardt disease. A workshop organized by the Foundation Fighting Blindness Clinical Research Institute was held on June 11, 2018, in Baltimore, MD, USA. Invited speakers discussed spectral-domain optical coherence tomography, fundus autofluorescence, and microperimetry methods and findings in the ProgStar prospective study. The workshop concluded with a panel discussion of optimal endpoints for measuring treatment efficacy in Stargardt disease. We summarize the workshop presentations in light of the most current literature on Stargardt disease and discuss potential clinical outcome measures and endpoints for future treatment trials.

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Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Cited by 26 publications

References 30 publications

Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations

Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations

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

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

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