TY - JOUR
T1 - Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy
T2 - Randomized PRIME Trial Outcomes
AU - Yu, Hannah J.
AU - Ehlers, Justis P.
AU - Sevgi, Duriye Damla
AU - Hach, Jenna
AU - O'Connell, Margaret
AU - Reese, Jamie L.
AU - Srivastava, Sunil K.
AU - Wykoff, Charles C.
N1 - Funding Information:
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and none were reported. FUNDING/SUPPORT: This research was supported by Regeneron Pharmaceuticals. FINANCIAL DISCLOSURES: Justis P. Ehlers is a consultant for Novartis, Oxurion, Allergan, Alcon, Regeneron, Roche, Genentech, Allegro, Zeiss, Leica; and has received research support from Regeneron, Novartis, Alcon, Genentech, Allergan, Zeiss, and Boehringer Ingelheim; and holds a patent assigned to Leica. Sunil K. Srivastava is a consultant for Novartis, Regeneron, Bausch & Lomb; and has received research support from Regeneron; and holds a patent assigned to Leica. Charles C Wykoff is a consultant for Acucela, Adverum, Alcon, Alimera Sciences, Allergan, Apellis, Arctic Vision, Bausch & Lomb, Bayer, Bionic Vision Technologies, Chengdu Kanghong Biotechnologies, Clearside Biomedical, DORC, Genentech, Gyroscope, IVERIC Bio, Kodiak Sciences, Merck, NGM Biopharmaceuticals, Novartis, ONL Therapeutics, Opthea, Oxurion, Palatin, Polyphotonix, RecensMedical, Regeneron, RegenXBio, Roche, Takeda, Thea Open Innovation, Verana Health; and has received research support from Adverum, Aerie Pharmaceuticals, Aldeyra, Apellis, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies, Clearside Biomedical, Gemini Therapeutics, Genentech, Graybug Vision, Gyroscope, IONIS Pharmaceutical, IVERIC Bio, Kodiak Sciences, LMRI, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Novartis, OccuRx, Opthea, Outlook Therapeutics, Recens Medical, Regeneron, RegenXBio, Roche, Santen, Senju, Taiwan Liposome Company, Xbrane BioPharma; and is a member of the speakers bureau for Regeneron. The other authors have no financial disclosures
Funding Information:
FUNDING/SUPPORT: This research was supported by Regeneron Pharmaceuticals.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - Purpose: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). Design: Prospective, randomized phase 2 trial (PRIME). Methods: A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. Results: Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P =. 49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. Conclusions: The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.
AB - Purpose: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). Design: Prospective, randomized phase 2 trial (PRIME). Methods: A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. Results: Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P =. 49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. Conclusions: The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.
UR - http://www.scopus.com/inward/record.url?scp=85103401279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103401279&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2021.01.024
DO - 10.1016/j.ajo.2021.01.024
M3 - Article
C2 - 33529593
AN - SCOPUS:85103401279
SN - 0002-9394
VL - 226
SP - 126
EP - 136
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -