A phase 2 placebo-controlled clinical trial with ACU-4429 (visual cycle modulator) for the treatment of dry age related macular degeneration (AMD): effect on drusen volume, measured with an optical coherence tomography device and a newly developed algorithm.
Final Report Abstract
The biggest surprise in the planned research project was that the pharmaceutical funding for the planned phase 2 clinical trial never materialized. I was fortunate that new optical coherence tomography (OCT) technologies were emerging. Swept-source OCT (SS-OCT) imaging enabled new insights into retinal diseases based on the larger field of view (widefield imaging) and the deeper tissue penetration (longer wavelength). Widefield imaging (9x12mm/12x12mm) turned out to be especially important when looking for reticular pseusodrusen (RPD)/subretinaldrusenoid deposits (SDDs), because they are preferably located inareas, which would not be captured on a central 6x6mm scancaptured with a commercially available SD-OCT instrument. RPD/SDDs are clinically relevant, and so is their diagnosis, because their presence in patients with AMD constitute a risk factor for progression to late AMD stages (geographic atrophy (GA) and/or macular neovascularization (MNV)). SD-OCT montage images as well as SS-OCT widefield scans can reliably demonstrate the RPD/SDD pattern, and when using a specific retinal en faceslab, RPD/SDD can now be easily diagnosed. Furthermore, we were able to demonstrate that SS-OCT widefield imaging was at least as good as conventional multimodal imaging (color, autofluorescence (AF), infrared reflectance imaging (IR)) in detecting RPD/SDDs, which justifies OCT imaging as a single method approach for diagnosing RPD/SDDs. A single scan takes only a few seconds to obtain,and contains all the information needed. In another research project, patients with intermediate AMD (iAMD) were followed over time to look at drusen changes and signs predicting drusen breakdown. We demonstrated a convenient time saving method to screen for signs of drusen breakdown (nascent geographic atrophy (nGA) by using the sub RPE en face slab rather than to have to scroll through all cross-sectional B-scans, which is the current method of choice. This sub RPE slab is located under the RPE and captures hypertransmissions of light into the choroid (a sign of RPE breakdown), and these areas appear as bright areas on the en faceslab image. It is of great importance to exclude patients with signs for nGAwhen studying new therapies for iAMD in clinical trials, and the use of the en face sub RPE slab imagingis an elegant screening strategy to detect and exclude these patients.
Publications
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.The Controversy of band #2. Retina Specialist, June 2015
Schaal KB, Rosenfeld PJ
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Widefield En Face Optical Coherence Tomography Imaging of SubretinalDrusenoid Deposits. Ophthalmic Surg Lasers Imaging Retina 2015;46(5):550-559
Schaal, Karen B.; Legarreta, Andrew D.; Gregori, Giovanni; Legarreta, John E.; Cheng, Qianqian; Stetson, Paul F.; Cai, Ming; Laron, Michal; Durbin, Mary & Rosenfeld, Philip J.
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Anatomic Clinical Trial Endpoints for Non-Exudative Age-Related Macular Degeneration. Ophthalmology. 2016;123(5):1060-79
Schaal, Karen B.; Rosenfeld, Philip J.; Gregori, Giovanni; Yehoshua, Zohar & Feuer, William J.
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Comparison between widefield en face swept-source OCT and conventional multimodal imaging for the detection of reticular pseudodrusen. Ophthalmology
Volume 124, Issue 2, February 2017, Pages 205-214
Schaal, Karen B.; Legarreta, Andrew D.; Feuer, William J.; Gregori, Giovanni; Cheng, Qianqian; Legarreta, John E.; Durbin, Mary K.; Stetson, Paul F.; Kubach, Sophie & Rosenfeld, Philip J.
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En face Optical Coherence Tomography Imaging for the Detection of Nascent Geographic Atrophy. American Journal of Ophthalmology
Volume 174, February 2017, Pages 145-154
Schaal, Karen B.; Gregori, Giovanni & Rosenfeld, Philip J.
